Review of Medical Microbiology and Immunology, 13th Edition

PART X. BRIEF SUMMARIES OF MEDICALLY IMPORTANT ORGANISMS

SUMMARIES OF MEDICALLY IMPORTANT BACTERIA

GRAM-POSITIVE COCCI (CHAPTER 15)

Staphylococcus aureus

Diseases—Abscesses of many organs, endocarditis, osteomyelitis, septic arthritis, and impetigo. Also hospital-acquired pneumonia, surgical wound infections, and sepsis. Also exotoxin-mediated diseases such as gastroenteritis (food poisoning), toxic shock syndrome, and scalded skin syndrome. It is one of the most common causes of human infections.

Characteristics—Gram-positive cocci in clusters. Coagulase-positive. Catalase-positive. Most isolates produce β-lactamase.

Habitat and Transmission—Main habitat is human nose; also found on human skin. Transmission is via the hands.

Pathogenesis—Abscess containing pus is the most common lesion. Three exotoxins are also made. Toxic shock syndrome toxin is a superantigen and causes toxic shock syndrome by stimulating many helper T cells to release large amounts of lymphokines, especially IL-2. Enterotoxin, which causes food poisoning, is also a superantigen. Food poisoning has a short incubation period because it is preformed in food. Scalded skin syndrome toxin is a protease that cleaves desmoglein in tight junctions in the skin. Protein A is an important virulence factor because it binds to the heavy chain of IgG and prevents the activation of complement. Predisposing factors to infection include breaks in the skin, foreign bodies such as sutures, neutrophil levels below 500/μL, intravenous drug use (predisposes to right-sided endocarditis), and tampon use (predisposes to toxic shock syndrome).

Laboratory Diagnosis—Gram-stained smear and culture. Yellow or gold colonies on blood agar; colonies often β-hemolytic. Staphylococcus aureus is coagulase-positive; Staphylococcus epidermidis is coagulase-negative. Serologic tests not useful.

Treatment—Penicillin G for sensitive isolates; β-lactamase–resistant penicillins such as nafcillin for resistant isolates; vancomycin for isolates resistant to nafcillin. About 85% are resistant to penicillin G. Plasmid-encoded β-lactamase mediates most resistance. Resistance to nafcillin is caused by changes in binding proteins. Some isolates are tolerant to penicillin. Rare vancomycin-resistant strains have emerged.

Prevention—Cefazolin is used to prevent surgical wound infections. No vaccine is available. Handwashing reduces spread.

Staphylococcus epidermidis

Diseases—Endocarditis on prosthetic heart valves, prosthetic hip infection, intravascular catheter infection, cerebrospinal fluid shunt infection, neonatal sepsis.

Characteristics—Gram-positive cocci in clusters. Coagulase-negative. Catalase-positive.

Habitat and Transmission—Normal flora of the human skin and mucous membranes. It is probably the patient’s own strains that cause infection, but transmission from person to person via hands may occur.

Pathogenesis—Glycocalyx-producing strains adhere well to foreign bodies such as prosthetic implants and catheters. It is a low-virulence organism that causes disease primarily in immunocompromised patients and in those with implants. It is a major cause of hospital-acquired infections. Unlike S. aureus, no exotoxins have been identified.

Laboratory Diagnosis—Gram-stained smear and culture. Whitish, nonhemolytic colonies on blood agar. It is coagulase-negative. S. epidermidis is sensitive to novobiocin, whereas the other coagulase-negative staphylococcus, Staphylococcus saprophyticus, is resistant. Serologic tests are not useful.

Treatment—Vancomycin plus either rifampin or an aminoglycoside. It produces β-lactamases and is resistant to many antibiotics.

Prevention—There is no drug or vaccine.

Staphylococcus saprophyticus

Gram-positive cocci in clusters. Coagulase-negative. Resistant to novobiocin in contrast to S. epidermidis, which is sensitive. Causes community-acquired urinary tract infections in young women (but Escherichia coli is a much more common cause).

Streptococcus pyogenes (Group A Streptococcus)

Diseases—Suppurative (pus-producing) diseases (e.g., pharyngitis and cellulitis); nonsuppurative (immunologic) diseases (e.g., rheumatic fever and acute glomerulonephritis).

Characteristics—Gram-positive cocci in chains. β-Hemolytic colonies. Catalase-negative. Bacitracin-sensitive. β-Hemolytic streptococci are subdivided into group A, B, etc., by differences in the antigenicity of their cell wall carbohydrate.

Habitat and Transmission—Habitat is the human throat and skin. Transmission is via respiratory droplets.

Pathogenesis—For suppurative infections, hyaluronidase (“spreading factor”) mediates subcutaneous spread seen in cellulitis; erythrogenic toxin (a superantigen) causes the rash of scarlet fever; M protein impedes phagocytosis. For nonsuppurative (immunologic) diseases, rheumatic fever is caused by immunologic cross-reaction between bacterial antigen and human heart and joint tissue (i.e., antibody against streptococcal M protein reacts with myosin in cardiac muscle), and acute glomerulonephritis is caused by immune complexes formed between streptococcal antigens and antibody to those antigens. The immune complexes are trapped by glomeruli, complement is activated, neutrophils are attracted to the site by C5a, and proteases produced by neutrophils damage glomeruli.

Laboratory Diagnosis—The diagnosis of suppurative infections (e.g., cellulitis) differs from immunologic diseases (e.g., rheumatic fever). For suppurative infections, use Gram-stained smear and culture. β-Hemolytic colonies on blood agar. (Hemolysis due to streptolysins O and S.) If isolate is sensitive to bacitracin, it is identified as Streptococcus pyogenes. Rapid ELISA tests for group A streptococcal antigens in throat swabs are available. Assay for antibody in patient’s serum is not done for suppurative infections. If rheumatic fever is suspected, patient’s antistreptolysin O (ASO) antibody titer is tested to determine whether previous exposure to S. pyogenes has occurred. If acute glomerulonephritis is suspected, antibody to streptococcal DNase B is used as evidence of a previous skin infection by S. pyogenes.

Treatment—Penicillin G (no significant resistance).

Prevention—Penicillin is used in patients with rheumatic fever to prevent recurrent S. pyogenes pharyngitis. This prevents additional damage to heart valves. There is no vaccine.

Streptococcus agalactiae (Group B Streptococcus)

Diseases—Neonatal meningitis and sepsis.

Characteristics—Gram-positive cocci in chains. β-Hemolytic colonies. Catalase-negative. Bacitracin-resistant. β-Hemolytic streptococci are subdivided into group A, B, etc., by differences in the antigenicity of their cell wall carbohydrate.

Habitat and Transmission—Main habitat is the human vagina. Transmission occurs during birth.

Pathogenesis—Pyogenic organism. No exotoxins identified. Predisposing factors to neonatal infection include rupture of membranes more than 18 hours before delivery, labor prior to 37 weeks (infant is premature), absence of maternal antibody, and heavy colonization of the genital tract by the organism.

Laboratory Diagnosis—Gram-stained smear and culture. β-Hemolytic (narrow zone) colonies on blood agar that are resistant to bacitracin. Organisms hydrolyze hippurate and are CAMP test–positive.

Treatment—Penicillin G.

Prevention—No vaccine. Ampicillin should be given to mothers if prolonged rupture of membranes occurs, if mother has a fever, or if the neonate is premature.

Enterococcus faecalis

Diseases—Urinary tract and biliary tract infections are most frequent. Endocarditis rare but life-threatening.

Characteristics—Gram-positive cocci in chains. Catalase-negative.

Habitat and Transmission—Habitat is the human colon; urethra and female genital tract can be colonized. May enter bloodstream during gastrointestinal (GI) or genitourinary tract procedures. May infect other sites (e.g., endocarditis).

Pathogenesis—No exotoxins or virulence factors identified.

Laboratory Diagnosis—Gram-stained smear and culture. α-, β-, or nonhemolytic colonies on blood agar. Grows in 6.5% NaCl and hydrolyzes esculin in the presence of 40% bile. Serologic tests not useful.

Treatment—Penicillin or vancomycin plus an aminoglycoside such as gentamicin is bactericidal. Organism is resistant to either drug given individually, but given together they have a synergistic effect. Aminoglycoside alone is ineffective because it cannot penetrate. Penicillin or vancomycin weakens the cell wall, allowing the aminoglycoside to penetrate. Vancomycin-resistant enterococci (VRE) are important causes of nosocomial (hospital-acquired) infections. Linezolid can be used to treat VRE.

Prevention—Penicillin and gentamicin should be given to patients with damaged heart valves prior to intestinal or urinary tract procedures. No vaccine is available.

Streptococcus pneumoniae (Pneumococcus)

Diseases—The most common diseases are pneumonia and meningitis in adults and otitis media and sinusitis in children.

Characteristics—Gram-positive “lancet-shaped” cocci in pairs (diplococci) or short chains. α-Hemolytic colonies. Catalase-negative. Growth is inhibited by optochin in contrast to viridans streptococci, which are resistant. Colonies are bile-soluble. Prominent polysaccharide capsule. Eighty-five serotypes based on antigenicity of polysaccharide capsule. One of the three classical encapsulated pyogenic bacteria (Neisseria meningitidis and Haemophilus influenzae are the other two).

Habitat and Transmission—Habitat is the human upper respiratory tract. Transmission is via respiratory droplets.

Pathogenesis—Induces inflammatory response. No known exotoxins. Polysaccharide capsule retards phagocytosis. Antipolysaccharide antibody opsonizes the organism and provides type-specific immunity. IgA protease degrades secretory IgA on respiratory mucosa, allowing colonization. Viral respiratory infection predisposes to pneumococcal pneumonia by damaging mucociliary elevator; splenectomy predisposes to sepsis. Skull fracture with spinal fluid leakage from nose predisposes to meningitis.

Laboratory Diagnosis—Gram-stained smear and culture. α-Hemolytic colonies on blood agar. Growth inhibited by bile and optochin. Quellung reaction occurs (swelling of capsule with type-specific antiserum). Serologic tests for antibody not useful. Tests for capsular antigen in spinal fluid and C polysaccharide in urine can be diagnostic.

Treatment—Penicillin G. Low-level and high-level resistance to penicillin is caused by alterations in penicillin-binding proteins. No β-lactamase is made.

Prevention—Two vaccines are available. The one used in adults contains capsular polysaccharide of the 23 serotypes that cause bacteremia most frequently. The other, which is used primarily in children under the age of 2 years, contains capsular polysaccharide of 13 serotypes coupled to carrier protein (diphtheria toxoid). Oral penicillin is used in immunocompromised children.

Viridans Group Streptococci (e.g., Streptococcus sanguis, Streptococcus mutans)

Diseases—Endocarditis is the most important disease. Also brain abscess, especially in mixed infections with mouth anaerobes. S. mutans implicated in dental caries.

Characteristics—Gram-positive cocci in chains. α-Hemolytic colonies. Catalase-negative. Growth is resistant to optochin in contrast to pneumococci, which are inhibited. Colonies are not dissolved by bile.

Habitat and Transmission—Habitat is the human oropharynx. Organism enters bloodstream during dental procedures.

Pathogenesis—Bacteremia from dental procedures spreads organism to damaged heart valves. Organism is protected from host defenses within vegetations. No known toxins. Glycocalyx composed of polysaccharide enhances adhesion to heart valves.

Laboratory Diagnosis—Gram-stained smear and culture. α-Hemolytic colonies on blood agar. Growth not inhibited by bile or optochin, in contrast to pneumococci. Viridans streptococci are classified into species by using various biochemical tests. Serologic tests not useful.

Treatment—Penicillin G with or without an aminoglycoside.

Prevention—Penicillin to prevent endocarditis in patients with damaged or prosthetic heart valves who undergo dental procedures.

GRAM-NEGATIVE COCCI (CHAPTER 16)

Neisseria meningitidis (Meningococcus)

Diseases—Meningitis and meningococcemia.

Characteristics—Gram-negative “kidney-bean” diplococci. Oxidase-positive. Large polysaccharide capsule. One of the three classic encapsulated pyogenic bacteria (Streptococcus pneumoniae and Haemophilus influenzae are the other two).

Habitat and Transmission—Habitat is the human upper respiratory tract; transmission is via respiratory droplets.

Pathogenesis—After colonizing the upper respiratory tract, the organism reaches the meninges via the bloodstream. Endotoxin in cell wall causes symptoms of septic shock seen in meningococcemia. No known exotoxins; IgA protease produced. Capsule is antiphagocytic. Deficiency in late complement components predisposes to recurrent meningococcal infections.

Laboratory Diagnosis—Gram-stained smear and culture. Oxidase-positive colonies on chocolate agar. Ferments maltose in contrast to gonococci, which do not. Serologic tests not useful.

Treatment—Penicillin G (no significant resistance).

Prevention—Vaccine contains capsular polysaccharide of strains A, C, Y, and W-135. One form of the vaccine contains the polysaccharides coupled to a carrier protein (diphtheria toxoid), and one contains only the polysaccharides. Rifampin or ciprofloxacin given to close contacts to decrease oropharyngeal carriage.

Neisseria gonorrhoeae (Gonococcus)

Disease—Gonorrhea. Also neonatal conjunctivitis and pelvic inflammatory disease.

Characteristics—Gram-negative “kidney-bean” diplococci. Oxidase-positive. Insignificant capsule.

Habitat and Transmission—Habitat is the human genital tract. Transmission in adults is by sexual contact. Transmission to neonates is during birth.

Pathogenesis—Organism invades mucous membranes and causes inflammation. Endotoxin present but weaker than that of meningococcus, so less severe disease when bacteremia occurs. No exotoxins identified. IgA protease and pili are virulence factors.

Laboratory Diagnosis—Gram-stained smear and culture. Organism visible intracellularly within neutrophils in urethral exudate. Oxidase-positive colonies on Thayer-Martin medium. Gonococci do not ferment maltose, whereas meningococci do. Serologic tests not useful. Nucleic acid amplification tests (NAAT) are used as a screening test in urogenital infections.

Treatment—Ceftriaxone for uncomplicated cases. Azithromycin or doxycycline added for urethritis caused by Chlamydia trachomatis. High-level resistance to penicillin is caused by plasmid-encoded penicillinase. Low-level resistance to penicillin is caused by reduced permeability and altered binding proteins.

Prevention—No drug or vaccine. Condoms offer protection. Trace contacts and treat to interrupt transmission. Treat eyes of newborns with erythromycin ointment or silver nitrate to prevent conjunctivitis.

GRAM-POSITIVE RODS (CHAPTER 17)

Bacillus anthracis

Disease—Anthrax.

Characteristics—Aerobic, gram-positive, spore-forming rods. Capsule composed of poly-D-glutamate. B. anthracis is the only medically important organism that has a capsule composed of amino acids rather than polysaccharides.

Habitat and Transmission—Habitat is soil. Transmission is by contact with infected animals or inhalation of spores from animal hair and wool.

Pathogenesis—Anthrax toxin consists of three proteins: edema factor, which is an adenylate cyclase; lethal factor, which kills cells by inhibiting a signal transduction protein involved in cell division; and protective antigen, which mediates the entry of the other two components into the cell. The capsule is antiphagocytic.

Laboratory Diagnosis—Gram-stained smear plus aerobic culture on blood agar. B. anthracis is nonmotile, in contrast to other Bacillus species. Rise in antibody titer in indirect hemagglutination test is diagnostic.

Treatment—Penicillin G (no significant resistance).

Prevention—Vaccine consisting of protective antigen is given to individuals in high-risk occupations.

Bacillus cereus

Disease—Food poisoning.

Characteristics—Aerobic, gram-positive, spore-forming rod.

Habitat and Transmission—Habitat is grains, such as rice. Spores survive boiling during preparation of rice, then germinate when rice is held at warm temperature.

Pathogenesis—Two enterotoxins are produced: one acts like cholera toxin (i.e., cyclic AMP is increased within enterocytes); the other acts like staphylococcal enterotoxin (i.e., it is a superantigen).

Laboratory Diagnosis—Not done.

Treatment—Symptomatic only.

Prevention—No vaccine.

Clostridium tetani

Disease—Tetanus.

Characteristics—Anaerobic, gram-positive, spore-forming rods. Spore is at one end (“terminal spore”) so organism looks like a tennis racket.

Habitat and Transmission—Habitat is the soil. Organism enters through traumatic breaks in the skin.

Pathogenesis—Spores germinate under anaerobic conditions in the wound. Organism produces exotoxin, which blocks release of inhibitory neurotransmitters (glycine and γ-aminobutyric acid [GABA]) from spinal neurons. Excitatory neurons are unopposed, and extreme muscle spasm (tetanus, spastic paralysis) results. “Lock-jaw” and “risus sardonicus” are two examples of the muscle spasms. Tetanus toxin (tetanospasmin) is a protease that cleaves proteins involved in the release of neurotransmitters.

Laboratory Diagnosis—Primarily a clinical diagnosis. Organism is rarely isolated. Serologic tests not useful.

Treatment—Hyperimmune human globulin to neutralize toxin. Also penicillin G and spasmolytic drugs (e.g., Valium). No significant resistance to penicillin.

Prevention—Toxoid vaccine (toxoid is formaldehyde-treated toxin). Usually given to children in combination with diphtheria toxoid and acellular pertussis vaccine (DTaP). If patient is injured and has not been immunized, give hyperimmune globulin plus toxoid (passive–active immunization). Debride wound. Give tetanus toxoid booster every 10 years.

Clostridium botulinum

Disease—Botulism.

Characteristics—Anaerobic, gram-positive, spore-forming rods.

Habitat and Transmission—Habitat is the soil. Organism and botulinum toxin transmitted in improperly preserved food.

Pathogenesis—Botulinum toxin is a protease that cleaves proteins involved in the release of acetylcholine at the myoneural junction, causing flaccid paralysis. Failure to sterilize food during preservation allows spores to survive. Spores germinate in anaerobic environment and produce toxin. The toxin is heat-labile; therefore, foods eaten without proper cooking are usually implicated.

Laboratory Diagnosis—Presence of toxin in patient’s serum or stool or in food. Detection of toxin involves either antitoxin in serologic tests or production of the disease in mice. Serologic tests for antibody in the patient are not useful.

Treatment—Antitoxin to types A, B, and E made in horses. Respiratory support may be required.

Prevention—Observing proper food preservation techniques, cooking all home-canned food, and discarding bulging cans.

Clostridium perfringens

Diseases—Gas gangrene (myonecrosis) and food poisoning.

Characteristics—Anaerobic, gram-positive, spore-forming rods.

Habitat and Transmission—Habitat is soil and human colon. Myonecrosis results from contamination of wound with soil or feces. Food poisoning is transmitted by ingestion of contaminated food.

Pathogenesis—Gas gangrene in wounds is caused by germination of spores under anaerobic conditions and the production of several cytotoxic factors, especially alpha toxin, a lecithinase that cleaves cell membranes. Gas in tissue (CO2 and H2) is produced by organism’s anaerobic metabolism. Food poisoning is caused by production of enterotoxin within the gut. Enterotoxin acts as a superantigen, similar to that of S. aureus.

Laboratory Diagnosis—Gram-stained smear plus anaerobic culture. Spores not usually seen in clinical specimens; the organism is growing, and nutrients are not restricted. Production of lecithinase is detected on egg yolk agar and identified by enzyme inhibition with specific antiserum. Serologic tests not useful.

Treatment—Penicillin G plus debridement of the wound in gas gangrene (no significant resistance to penicillin). Only symptomatic treatment needed in food poisoning.

Prevention—Extensive debridement of the wound plus administration of penicillin decreases probability of gas gangrene. There is no vaccine.

Clostridium difficile

Disease—Pseudomembranous colitis.

Characteristics—Anaerobic, gram-positive, spore-forming rods.

Habitat and Transmission—Habitat is the human colon. Transmission is fecal–oral.

Pathogenesis—Antibiotics suppress normal flora of colon, allowing C. difficile to overgrow and produce large amounts of exotoxins. Exotoxins A and B inhibit GTPases, causing inhibition of signal transduction and depolymerization of actin filaments. This leads to apoptosis and death of enterocytes. The pseudomembranes seen in the colon are the visual result of the death of enterocytes.

Laboratory Diagnosis—Exotoxin in the stool is typically detected by using known antibody to the toxin in an ELISA test or by polymerase chain reaction (PCR) assay. Exotoxin in stool can also be detected by cytopathic effect on cultured cells. Identified by neutralization of cytopathic effect with known antibody.

Treatment—Metronidazole. Vancomycin, although effective, should not be used because it may select for vancomycin-resistant enterococci.

Prevention—No vaccine or drug is available.

Corynebacterium diphtheriae

Disease—Diphtheria.

Characteristics—Club-shaped gram-positive rods arranged in V or L shape. Granules stain metachromatically. Aerobic, non–spore-forming organism.

Habitat and Transmission—Habitat is the human throat. Transmission is via respiratory droplets.

Pathogenesis—Organism secretes an exotoxin that inhibits protein synthesis by adding ADP-ribose to elongation factor-2 (EF-2). Toxin has two components: subunit A, which has the ADP-ribosylating activity, and subunit B, which binds the toxin to cell surface receptors. Pseudomembrane in throat caused by death of mucosal epithelial cells.

Laboratory Diagnosis—Gram-stained smear and culture. Black colonies on tellurite plate. Document toxin production with precipitin test or by disease produced in laboratory animals. Serologic tests not useful.

Treatment—Antitoxin made in horses neutralizes the toxin. Penicillin G kills the organism. No significant resistance to penicillin.

Prevention—Toxoid vaccine (toxoid is formaldehyde-treated toxin), usually given to children in combination with tetanus toxoid and acellular pertussis vaccine (DTaP).

Listeria monocytogenes

Diseases—Meningitis and sepsis in newborns and immunocompromised adults. Gastroenteritis.

Characteristics—Small gram-positive rods. Aerobic, non–spore-forming organism.

Habitat and Transmission—Organism colonizes the GI and female genital tracts; in nature, it is widespread in animals, plants, and soil. Transmission is across the placenta or by contact during delivery. Outbreaks of sepsis in neonates and gastroenteritis in the general population are related to ingestion of unpasteurized milk products (e.g., cheese).

Pathogenesis—Listeriolysin is an exotoxin that degrades cell membranes. Reduced cell-mediated immunity and immunologic immaturity as in neonates predispose to disease. Intracellular pathogen that moves from cell-to-cell via “actin rockets.”

Laboratory Diagnosis—Gram-stained smear and culture. Small, β-hemolytic colonies on blood agar. Tumbling motility. Serologic tests not useful.

Treatment—Ampicillin with or without gentamicin.

Prevention—Pregnant women and immunocompromised patients should not ingest unpasteurized milk products or raw vegetables. Trimethoprim-sulfamethoxazole given to immunocompromised patients to prevent Pneumocystis pneumonia also can prevent listeriosis. No vaccine is available.

GRAM-NEGATIVE RODS RELATED TO THE ENTERIC TRACT (CHAPTER 18)

Escherichia coli

Diseases—Urinary tract infection (UTI), sepsis, neonatal meningitis, and “traveler’s diarrhea” are the most common.

Characteristics—Facultative gram-negative rods; ferment lactose.

Habitat and Transmission—Habitat is the human colon; it colonizes the vagina and urethra. From the urethra, it ascends and causes UTI. Acquired during birth in neonatal meningitis and by the fecal–oral route in diarrhea.

Pathogenesis—Endotoxin in cell wall causes septic shock. Two enterotoxins are produced by enterotoxigenic E.coli (ETEC) strains. The heat-labile toxin (LT) stimulates adenylate cyclase by ADP-ribosylation. Increased cyclic AMP causes outflow of chloride ions and water, resulting in diarrhea. The heat-stable toxin (ST) causes diarrhea, perhaps by stimulating guanylate cyclase. Virulence factors include pili for attachment to mucosal surfaces and a capsule that impedes phagocytosis. Shiga toxin (verotoxin) is an enterotoxin produced by E. coli strains (STEC) with the O157:H7 serotype. It causes bloody diarrhea and hemolytic-uremic syndrome associated with eating undercooked meat. Shiga toxin (verotoxin) inhibits protein synthesis by removing adenine from the 28S rRNA of human ribosomes.

Predisposing factors to UTI in women include the proximity of the anus to the vagina and urethra, as well as a short urethra. This leads to colonization of the urethra and vagina by the fecal flora. Abnormalities (e.g., strictures, valves, and stones) predispose as well. Indwelling urinary catheters and intravenous lines predispose to UTI and sepsis, respectively. Colonization of the vagina leads to neonatal meningitis acquired during birth. The main virulence factor for neonatal meningitis is the K1 capsular polysaccharide.

Laboratory Diagnosis—Gram-stained smear and culture. Lactose-fermenting colonies on eosin–methylene blue (EMB) or MacConkey’s agar. Green sheen on EMB agar. Triple sugar iron (TSI) agar shows acid slant and acid butt with gas but no H2S. Differentiate from other lactose-positive organisms by biochemical reactions. For epidemiologic studies, type organism by O and H antigens by using known antisera. Serologic tests for antibodies in patient’s serum not useful.

Treatment—Ampicillin or sulfonamides for UTIs. Third-generation cephalosporins for meningitis and sepsis. Rehydration is effective in traveler’s diarrhea; trimethoprim-sulfamethoxazole may shorten duration of symptoms. Antibiotic resistance mediated by plasmid-encoded enzymes (e.g., β-lactamase and aminoglycoside-modifying enzymes).

Prevention—Prevention of UTI involves limiting the frequency and duration of urinary catheterization. Prevention of sepsis involves promptly removing or switching sites of intravenous lines. Traveler’s diarrhea is prevented by eating only cooked food and drinking boiled water in certain countries. Prophylactic doxycycline or Pepto-Bismol may prevent traveler’s diarrhea. There is no vaccine that prevents any of the diseases caused by E. coli.

Salmonella typhi

Disease—Typhoid fever.

Characteristics—Facultative gram-negative rods. Non–lactose-fermenting. Produces H2S.

Habitat and Transmission—Habitat is the human colon only, in contrast to other salmonellae, which are found in the colon of animals as well. Transmission is by the fecal–oral route.

Pathogenesis—Infects the cells of the reticuloendothelial system, especially in the liver and spleen. Endotoxin in cell wall causes fever. Capsule (Vi antigen) is a virulence factor. No exotoxins known. Decreased stomach acid resulting from ingestion of antacids or gastrectomy predisposes to Salmonella infections. Chronic carrier state established in gallbladder. Organism excreted in bile results in fecal–oral spread to others.

Laboratory Diagnosis—Gram-stained smear and culture. Non–lactose-fermenting colonies on EMB or MacConkey’s agar. TSI agar shows alkaline slant and acid butt, with no gas and a small amount of H2S. Biochemical and serologic reactions used to identify species. Identity can be determined by using known antisera against O, H, and Vi antigens in agglutination test. Widal test detects agglutinating antibodies to O and H antigens in patient’s serum, but its use is limited.

Treatment—Most effective drug is ceftriaxone. Ampicillin and trimethoprim-sulfamethoxazole can be used in patients who are not severely ill. Resistance to chloramphenicol and ampicillin is mediated by plasmid-encoded acetylating enzymes and β-lactamase, respectively.

Prevention—Public health measures (e.g., sewage disposal, chlorination of the water supply, stool cultures for food handlers, and handwashing prior to food handling). Two vaccines are in common use; one vaccine contains purified Vi polysaccharide capsule as the immunogen and the other contains live, attenuated S. typhi as the immunogen.

Salmonella enterica (often called Salmonella enteritidis)

Diseases—Enterocolitis. Sepsis with metastatic abscesses occasionally.

Characteristics—Facultative gram-negative rods. Non–lactose-fermenting. Produces H2S. Motile, in contrast to Shigella. More than 1500 serotypes.

Habitat and Transmission—Habitat is the enteric tract of humans and animals (e.g., chickens and domestic livestock). Transmission is by the fecal–oral route.

Pathogenesis—Invades the mucosa of the small and large intestines. Can enter blood, causing sepsis. Infectious dose is at least 100,000 organisms, much greater than the infectious dose of Shigella. Infectious dose is high because organism is inactivated by stomach acid. Endotoxin in cell wall; no exotoxin. Predisposing factors include lowered stomach acidity from either antacids or gastrectomy. Sickle cell anemia predisposes to Salmonella osteomyelitis.

Laboratory Diagnosis—Gram-stained smear and culture. Non–lactose-fermenting colonies on EMB or MacConkey’s agar. TSI agar shows alkaline slant and acid butt, with gas and H2S. Biochemical and serologic reactions used to identify species. Can identify the organism by using known antisera in agglutination assay. Widal test detects antibodies in patient’s serum to the O and H antigens of the organism but is not widely used.

Treatment—Antibiotics usually not recommended for uncomplicated enterocolitis. Ceftriaxone or other drugs are used for sepsis, depending on sensitivity tests. Resistance to ampicillin and chloramphenicol is mediated by plasmid-encoded β-lactamases and acetylating enzymes, respectively.

Prevention—Public health measures (e.g., sewage disposal, chlorination of the water supply, stool cultures for food handlers, and handwashing prior to food handling). Do not eat raw eggs or meat. No vaccine is available.

Shigella species (e.g., Shigella dysenteriae, Shigella sonnei)

Disease—Enterocolitis (dysentery).

Characteristics—Facultative gram-negative rods. Non–lactose-fermenting. Nonmotile, in contrast to Salmonella.

Habitat and Transmission—Habitat is the human colon only; unlike Salmonella enterica, there are no animal carriers for Shigella. Transmission is by the fecal–oral route.

Pathogenesis—Invades the mucosa of the ileum and colon but does not penetrate farther; therefore, sepsis is rare. Endotoxin in cell wall. Infectious dose is much lower (1–10 organisms) than that of Salmonella. The infectious dose of Shigella is low because it is resistant to stomach acid. Children in mental institutions and day care centers experience outbreaks of shigellosis. No chronic carrier state.

Laboratory Diagnosis—Gram-stained smear and culture. Non–lactose-fermenting colonies on EMB or MacConkey’s agar. TSI agar shows an alkaline slant with an acid butt and no gas or H2S. Identified by biochemical reactions or by serology with anti-O antibody in agglutination test. Serologic tests for antibodies in the patient’s serum are not done.

Treatment—In most cases, fluid and electrolyte replacement only. In severe cases, ciprofloxacin. Resistance is mediated by plasmid-encoded enzymes (e.g., β-lactamase, which degrades ampicillin, and a mutant pteroate synthetase, which reduces sensitivity to sulfonamides).

Prevention—Public health measures (e.g., sewage disposal, chlorination of the water supply, stool cultures for food handlers, and handwashing prior to food handling). Prophylactic drugs not used. No vaccine is available.

Vibrio cholerae

Disease—Cholera.

Characteristics—Comma-shaped gram-negative rods. Oxidase-positive, which distinguishes them from Enterobacteriaceae.

Habitat and Transmission—Habitat is the human colon and shellfish. Transmission is by the fecal–oral route.

Pathogenesis—Massive, watery diarrhea caused by enterotoxin that activates adenylate cyclase by adding ADP-ribose to the stimulatory G protein. Increase in cyclic AMP causes outflow of chloride ions and water. Toxin has two components: subunit A, which has the ADP-ribosylating activity; and subunit B, which binds the toxin to cell surface receptors. Organism produces mucinase, which enhances attachment to the intestinal mucosa. Role of endotoxin is unclear. Infectious dose is high (>107 organisms). Carrier state rare.

Laboratory Diagnosis—Gram-stained smear and culture. (During epidemics, cultures not necessary.) Agglutination of the isolate with known antisera confirms the identification.

Treatment—Treatment of choice is fluid and electrolyte replacement. Tetracycline is not necessary but shortens duration and reduces carriage.

Prevention—Public health measures (e.g., sewage disposal, chlorination of the water supply, stool cultures for food handlers, and handwashing prior to food handling). Vaccine containing killed cells has limited effectiveness. Tetracycline used for close contacts.

Vibrio parahaemolyticus

Comma-shaped gram-negative rod found in warm sea water. Causes watery diarrhea. Acquired by eating contaminated raw seafood. Outbreaks have occurred on cruise ships in Caribbean. Diarrhea is mediated by enterotoxin similar to cholera toxin.

Vibrio vulnificus

Comma-shaped gram-negative rod found in warm sea water. Causes cellulitis and life-threatening sepsis with hemorrhagic bullae. Acquired either by trauma to skin, especially in shellfish handlers, or by ingestion of raw shellfish, especially in patients who are immunocompromised or have reduced complement caused by liver damage.

Campylobacter jejuni

Disease—Enterocolitis.

Characteristics—Comma-shaped gram-negative rods. Microaerophilic. Grows well at 42°C.

Habitat and Transmission—Habitat is human and animal feces. Transmission is by the fecal–oral route.

Pathogenesis—Invades mucosa of the colon but does not penetrate; therefore, sepsis rarely occurs. No enterotoxin known.

Laboratory Diagnosis—Gram-stained smear plus culture on special agar (e.g., Skirrow’s agar) at 42°C in high-CO2, low-O2 atmosphere. Serologic tests not useful.

Treatment—Usually symptomatic treatment only; erythromycin for severe disease.

Prevention—Public health measures (e.g., sewage disposal, chlorination of the water supply, stool cultures for food handlers, and handwashing prior to food handling). No preventive vaccine or drug is available.

Helicobacter pylori

Disease—Gastritis and peptic ulcer. Risk factor for gastric carcinoma.

Characteristics—Curved gram-negative rod.

Habitat and Transmission—Habitat is the human stomach. Transmission is by ingestion.

Pathogenesis—Organisms synthesize urease, which produces ammonia that damages gastric mucosa. Ammonia also neutralizes acid pH in stomach, which allows the organism to live in gastric mucosa.

Laboratory Diagnosis—Gram stain and culture. Urease-positive. Serologic tests for antibody and the “urea breath” test are useful.

Treatment—Amoxicillin, metronidazole, and bismuth (Pepto-Bismol).

Prevention—No vaccine or drug is available.

Klebsiella pneumoniae

Diseases—Pneumonia, UTI, and sepsis.

Characteristics—Facultative gram-negative rods with large polysaccharide capsule.

Habitat and Transmission—Habitat is the human upper respiratory and enteric tracts. Organism is transmitted to the lungs by aspiration from upper respiratory tract and by inhalation of respiratory droplets. It is transmitted to the urinary tract by ascending spread of fecal flora.

Pathogenesis—Endotoxin causes fever and shock associated with sepsis. No exotoxin known. Organism has large capsule, which impedes phagocytosis. Chronic pulmonary disease predisposes to pneumonia; catheterization predisposes to UTI.

Laboratory Diagnosis—Gram-stained smear and culture. Characteristic mucoid colonies are a consequence of the organism’s abundant polysaccharide capsule. Lactose-fermenting colonies on MacConkey’s agar. Differentiated from Enterobacter and Serratia by biochemical reactions.

Treatment—Cephalosporins alone or with aminoglycosides, but antibiotic sensitivity testing must be done. Resistance is mediated by plasmid-encoded enzymes, especially β-lactamase.

Prevention—No vaccine or drug is available. Urinary and intravenous catheters should be removed promptly.

Enterobacter cloacae

Enteric gram-negative rod similar to K. pneumoniae. Causes hospital-acquired pneumonia, UTI, and sepsis. Highly antibiotic-resistant.

Serratia marcescens

Enteric gram-negative rod similar to K. pneumoniae. Causes hospital-acquired pneumonia, UTI, and sepsis. Red-pigmented colonies. Highly antibiotic-resistant.

Proteus species (e.g., Proteus vulgaris, Proteus mirabilis)

Diseases—UTI and sepsis.

Characteristics—Facultative gram-negative rods. Non–lactose-fermenting. Highly motile. Produce urease, as do Morganella and Providencia species (see later). Antigens of OX strains of P. vulgaris cross-react with many rickettsiae.

Habitat and Transmission—Habitat is the human colon and the environment (soil and water). Transmission to urinary tract is by ascending spread of fecal flora.

Pathogenesis—Endotoxin causes fever and shock associated with sepsis. No exotoxins known. Urease is a virulence factor because it degrades urea to produce ammonia, which raises the pH. This leads to “struvite” stones, which can obstruct urine flow, damage urinary epithelium, and serve as a nidus for recurrent infection by trapping bacteria within the stone. Organism is highly motile, which may facilitate entry into the bladder. Predisposing factors are colonization of the vagina, urinary catheters, and abnormalities of the urinary tract such as strictures, valves, and stones.

Laboratory Diagnosis—Gram-stained smear and culture. “Swarming” (spreading) effect over blood agar plate as a consequence of the organism’s active motility. Non–lactose-fermenting colonies on EMB or MacConkey’s agar. TSI agar shows an alkaline slant and acid butt with H2S. Organism produces urease, whereas Salmonella, which can appear similar on TSI agar, does not. Serologic tests not useful. P. mirabilis is indole-negative, whereas P. vulgaris, M. morganii, and Providencia species are indole-positive.

Treatment—Trimethoprim-sulfamethoxazole or ampicillin is often used for uncomplicated UTIs, but a third-generation cephalosporin should be used for serious infections. The indole-negative species P. mirabilis is more likely to be sensitive to antibiotics such as ampicillin than are the indole-positive species. Antibiotic sensitivities should be tested. Resistance is mediated by plasmid-encoded enzymes.

Prevention—No vaccine or drug is available. Prompt removal of urinary catheters helps prevent UTIs.

Morganella morganii

Enteric gram-negative rod similar to Proteus species. Causes UTIs and sepsis. Highly motile and produces urease. Indole-positive and more resistant to antibiotics than P. mirabilis.

Providencia rettgeri

Enteric gram-negative rod similar to Proteus species. Causes UTIs and sepsis. Highly motile and produces urease. Indole-positive and more resistant to antibiotics than P. mirabilis.

Pseudomonas aeruginosa

Diseases—Wound infection, UTI, pneumonia, and sepsis. One of the most important causes of nosocomial infections, especially in burn patients and those with cystic fibrosis. Causes endocarditis in intravenous drug users.

Characteristics—Aerobic gram-negative rods. Non–lactose-fermenting. Pyocyanin (blue-green) pigment produced. Oxidase-positive, which distinguishes it from members of the Enterobacteriaceae family.

Habitat and Transmission—Habitat is environmental water sources (e.g., in hospital respirators and humidifiers). Also inhabits the skin, upper respiratory tract, and colon of about 10% of people. Transmission is via water aerosols, aspiration, and fecal contamination.

Pathogenesis—Endotoxin is responsible for fever and shock associated with sepsis. Produces exotoxin A, which acts like diphtheria toxin (inactivates EF-2). Pili and capsule are virulence factors that mediate attachment and inhibit phagocytosis, respectively. Glycocalyx-producing strains predominate in chronic infections in cystic fibrosis patients. Strains with type III secretion systems are more virulent than those without. Severe burns and neutropenia are important predisposing factors.

Laboratory Diagnosis—Gram-stained smear and culture. Non–lactose-fermenting colonies on EMB or MacConkey’s agar. TSI agar shows an alkaline slant and an alkaline butt because the sugars are not fermented. Oxidase-positive. Serologic tests not useful.

Treatment—Antibiotics must be chosen on the basis of antibiotic sensitivities because resistance is common. Anti-pseudomonal penicillin and aminoglycoside are often used. Resistance is mediated by a variety of plasmid-encoded enzymes (e.g., β-lactamases and acetylating enzymes).

Prevention—Disinfection of water-related equipment in the hospital, handwashing, and prompt removal of urinary and intravenous catheters. There is no vaccine.

Burkholderia cepacia

Gram-negative rod resembling P. aeruginosa. Important cause of chronic infections in patients with cystic fibrosis. Formerly called Pseudomonas cepacia.

Stenotrophomonas maltophilia

Gram-negative rod resembling P. aeruginosa. Important cause of chronic infections in patients with cystic fibrosis. Formerly called Pseudomonas maltophilia.

Bacteroides fragilis

Diseases—Sepsis, peritonitis, and abdominal abscess.

Characteristics—Anaerobic, gram-negative rods.

Habitat and Transmission—Habitat is the human colon, where it is the predominant anaerobe. Transmission occurs by spread from the colon to the blood or peritoneum.

Pathogenesis—Lipopolysaccharide in cell wall is chemically different from and less potent than typical endotoxin. No exotoxins known. Capsule is antiphagocytic and promotes abscess formation. Predisposing factors to infection include bowel surgery and penetrating abdominal wounds.

Laboratory Diagnosis—Gram-stained smear plus anaerobic culture. Identification based on biochemical reactions and gas chromatography. Serologic tests not useful.

Treatment—Metronidazole, clindamycin, and cefoxitin are all effective. Abscesses should be surgically drained. Resistance to penicillin G, some cephalosporins, and aminoglycosides is common. Plasmid-encoded β-lactamase mediates resistance to penicillin.

Prevention—In bowel surgery, perioperative cefoxitin can reduce the frequency of postoperative infections. No vaccine is available.

Prevotella melaninogenica

Anaerobic gram-negative rod resembling B. fragilis. Member of normal flora found primarily above the diaphragm (e.g., mouth) in contrast to B. fragilis, which is found below (e.g., colon). Often involved in brain and lung abscesses. Formerly called Bacteroides melaninogenicus.

GRAM-NEGATIVE RODS RELATED TO THE RESPIRATORY TRACT (CHAPTER 19)

Haemophilus influenzae

Diseases—Sinusitis, otitis media, and pneumonia are common. Epiglottitis is uncommon, but H. influenzae is the most important cause. H. influenzae used to be a leading cause of meningitis, but the vaccine has greatly reduced the number of cases.

Characteristics—Small gram-negative (coccobacillary) rods. Requires factors X (hemin) and V (NAD) for growth. Of the six capsular polysaccharide types, type b causes 95% of invasive disease. Type b capsule is polyribitol phosphate.

Habitat and Transmission—Habitat is the upper respiratory tract. Transmission is via respiratory droplets.

Pathogenesis—Polysaccharide capsule is the most important determinant of virulence. Unencapsulated (“untypeable”) strains cause mucosal infections but not invasive infections. IgA protease is produced. Most cases of meningitis occur in children younger than 2 years of age, because maternal antibody has waned and the immune response of the child to capsular polysaccharides can be inadequate. No exotoxins identified.

Laboratory Diagnosis—Gram-stained smear plus culture on chocolate agar. Growth requires both factors X and V. Determine serotype by using antiserum in various tests (e.g., latex agglutination). Capsular antigen can be detected in serum or cerebrospinal fluid. Serologic test for antibodies in patient’s serum not useful.

Treatment—Ceftriaxone is the treatment of choice for meningitis. Approximately 25% of strains produce β-lactamase.

Prevention—Vaccine containing the type b capsular polysaccharide conjugated to diphtheria toxoid or other protein is given between 2 and 18 months of age. Rifampin can prevent meningitis in close contacts.

Bordetella pertussis

Disease—Whooping cough (pertussis).

Characteristics—Small gram-negative rods.

Habitat and Transmission—Habitat is the human respiratory tract. Transmission is via respiratory droplets.

Pathogenesis—Pertussis toxin stimulates adenylate cyclase by adding ADP-ribose onto the inhibitory G protein. Toxin has two components: subunit A, which has the ADP-ribosylating activity, and subunit B, which binds the toxin to cell surface receptors. Pertussis toxin causes lymphocytosis in the blood by inhibiting chemokine receptors. Inhibition of these receptors prevents lymphocytes from entering tissue, resulting in large numbers being retained in the blood. Inhibition of chemokine receptors occurs because pertussis toxin ADP-ribosylates the inhibitory G protein which prevents signal transduction within the cell. In addition, extracellular adenylate cyclase is produced, which can inhibit killing by phagocytes. Tracheal cytotoxin damages ciliated epithelium of respiratory tract.

Laboratory Diagnosis—Gram-stained smear plus culture on Bordet-Gengou agar. Identified by biochemical reactions and slide agglutination with known antisera. PCR tests, if available, are both sensitive and specific. Serologic tests for antibody in patient’s serum not useful.

Treatment—Azithromycin.

Prevention—The acellular vaccine containing pertussis toxoid and four other purified proteins is recommended rather than the killed vaccine, which contains whole organisms. Usually given to children in combination with diphtheria and tetanus toxoids (DTaP). Azithromycin is useful in unimmunized people who are known to be exposed.

Legionella pneumophila

Disease—Legionnaires’ disease (“atypical” pneumonia).

Characteristics—Gram-negative rods, but stain poorly with standard Gram stain. Require increased iron and cysteine for growth in culture. Sixteen serogroups; most cases caused by serogroup 1.

Habitat and Transmission—Habitat is environmental water sources. Transmission is via aerosol from the water source. Person-to-person transmission does not occur.

Pathogenesis—Aside from endotoxin, no toxins, enzymes, or virulence factors are known. Predisposing factors include being older than 55 years of age, smoking, and having a high alcohol intake. Immunosuppressed patients (e.g., renal transplant recipients) are highly susceptible. The organism replicates intracellularly; therefore, cell-mediated immunity is an important host defense. Smoking damages alveolar macrophages, which explains why it predisposes to pneumonia.

Laboratory Diagnosis—Microscopy with silver impregnation stain or fluorescent antibody. Culture on charcoal yeast extract agar containing increased amounts of iron and cysteine. Urinary antigen provides rapid diagnosis for serogroup 1 bacteria only. Diagnosis can be made serologically by detecting rise in antibody titer in patient’s serum.

Treatment—Azithromycin or erythromycin. Rifampin can be added in severe cases.

Prevention—No vaccine or prophylactic drug is available.

GRAM-NEGATIVE RODS RELATED TO ANIMAL SOURCES (ZOONOTIC ORGANISMS) (CHAPTER 20)

Brucella species (e.g., Brucella abortus, Brucella suis, Brucella melitensis)

Disease—Brucellosis (undulant fever).

Characteristics—Small gram-negative rods.

Habitat and Transmission—Reservoir is domestic livestock. Transmission is via unpasteurized milk and cheese or direct contact with the infected animal.

Pathogenesis—Organisms localize in reticuloendothelial cells, especially the liver and spleen. Able to survive and replicate intracellularly. No exotoxins. Predisposing factors include consuming unpasteurized dairy products and working in an abattoir.

Laboratory Diagnosis—Gram-stained smear plus culture on blood agar plate. Identified by biochemical reactions and by agglutination with known antiserum. Diagnosis may be made serologically by detecting antibodies in patient’s serum.

Treatment—Tetracycline plus rifampin.

Prevention—Pasteurize milk; vaccinate cattle. No human vaccine is available.

Francisella tularensis

Disease—Tularemia.

Characteristics—Small gram-negative rods.

Habitat and Transmission—Reservoir is many species of wild animals, especially rabbits, deer, and rodents. Transmission is by ticks (e.g., Dermacentor), aerosols, contact, and ingestion.

Pathogenesis—Organisms localize in reticuloendothelial cells. No exotoxins.

Laboratory Diagnosis—Culture is rarely done because special media are required and there is a high risk of infection of laboratory personnel. Diagnosis is usually made by serologic tests that detect antibodies in patient’s serum.

Treatment—Streptomycin.

Prevention—Live, attenuated vaccine for persons in high-risk occupations. Protect against tick bites.

Pasteurella multocida

Disease—Wound infection (e.g., cellulitis).

Characteristics—Small gram-negative rods.

Habitat and Transmission—Reservoir is the mouth of many animals, especially cats and dogs. Transmission is by animal bites.

Pathogenesis—Spreads rapidly in skin and subcutaneous tissue. No exotoxins.

Laboratory Diagnosis—Gram-stained smear and culture.

Treatment—Penicillin G.

Prevention—Ampicillin should be given to individuals with cat bites. There is no vaccine.

Yersinia pestis

Disease—Bubonic and pneumonic plague.

Characteristics—Small gram-negative rods with bipolar (“safety pin”) staining. One of the most virulent organisms (i.e., very low ID50).

Habitat and Transmission—Reservoir is wild rodents (e.g., rats, prairie dogs, and squirrels). Transmission is by flea bite.

Pathogenesis—Virulence factors include endotoxin, an exotoxin, two antigens (V and W), and an envelope (capsular) antigen that protects against phagocytosis. V and W proteins allow organism to grow within cells. Bubo is a swollen inflamed lymph node, usually located in the region of the flea bite.

Laboratory Diagnosis—Gram-stained smear. Other stains (e.g., Wayson’s) show typical “safety-pin” appearance more clearly. Cultures are hazardous and should be done only in specially equipped laboratories. Organism is identified by immunofluorescence. Diagnosis can be made by serologic tests that detect antibody in patient’s serum.

Treatment—Streptomycin either alone or in combination with doxycycline. Strict quarantine for 72 hours.

Prevention—Control rodent population and avoid contact with dead rodents. Killed vaccine is available for persons in high-risk occupations. Close contacts should be given tetracycline.

Bartonella henselae

Disease—Cat-scratch disease (CSD) and bacillary angiomatosis (BA).

Characteristics—Small gram-negative rod.

Habitat and Transmission—Reservoir is the cat’s mouth and transmitted by scratch or bite.

Pathogenesis—Low virulence organism. CSD is self-limited in immunocompetent, but BA occurs in immunocompromised individuals.

Laboratory Diagnosis—Diagnosis of CSD usually made by serologic tests. Biopsy of BA lesion shows pleomorphic rods using Warthin-Starry stain.

Treatment—None for CSD. Doxycycline or erythromycin for BA.

Prevention—No vaccine.

MYCOBACTERIA (CHAPTER 21)

Mycobacterium tuberculosis

Diseases—Tuberculosis.

Characteristics—Aerobic, acid-fast rods. High lipid content of cell wall, which prevents dyes used in Gram stain from staining organism. Lipids include mycolic acids and wax D. Grows very slowly, which requires that drugs be present for long periods (months). Produces catalase, which is required to activate isoniazid to the active drug.

Habitat and Transmission—Habitat is the human lungs. Transmission is via respiratory droplets produced by coughing.

Pathogenesis—Granulomas and caseation mediated by cellular immunity (i.e., macrophages and CD4-positive T cells [delayed hypersensitivity]). Cord factor (trehalose mycolate) correlates with virulence. No exotoxins or endotoxin. Suppression of cell-mediated immunity increases risk of reactivation and dissemination.

Laboratory Diagnosis—Acid-fast rods seen with Ziehl-Neelsen (or Kinyoun) stain. Slow-growing (3–6 weeks) colony on Löwenstein-Jensen medium. Organisms produce niacin and are catalase-positive. Serologic tests for antibody in patient’s serum not useful.

Skin Test—Purified protein derivative (PPD) skin test is positive if induration measuring 10 mm or more appears 48 hours after inoculation. Induration is caused by a delayed hypersensitivity response. Positive skin test indicates that the person has been infected but not necessarily that the person has the disease tuberculosis.

Treatment—Long-term therapy (6–9 months) with three drugs, isoniazid, rifampin, and pyrazinamide. A fourth drug, ethambutol, is used in severe cases (e.g., meningitis), in immunocompromised patients (e.g., those with AIDS), and where the chance of isoniazid-resistant organisms is high, as in Southeast Asians. Most patients become noninfectious within 2 weeks of adequate therapy. Treatment of latent (asymptomatic) infections consists of isoniazid taken for 6 to 9 months or isoniazid plus rifapentine for 3 months. Multidrug-resistant (MDR) strains have emerged and require other drug combinations.

Prevention—Bacillus Calmette-Guérin (BCG) vaccine containing live, attenuated Mycobacterium bovis organisms may prevent or limit extent of disease but does not prevent infection with M. tuberculosis. Vaccine used rarely in the United States but widely used in parts of Europe and Asia.

Atypical Mycobacteria

These mycobacteria are called atypical because they differ from M. tuberculosis in various ways. The most important difference is that the atypicals are found in the environment, whereas M. tuberculosis is found only in humans. The atypicals are also called “Mycobacteria other than M. tuberculosis,” or MOTTS.

The atypicals are subdivided into slow growers and rapid growers based on whether they form colonies in more than or less than 7 days. (Pigment production by the slow growers need not concern us here.)

The following are important slow growers:

(1) Mycobacterium avium-intracellulare complex (MAC) causes tuberculosis-like disease, especially in immunocompromised patients, such as those with AIDS. It is highly antibiotic-resistant.

(2) Mycobacterium kansasii also causes tuberculosis-like disease but is less antibiotic-resistant than MAC.

(3) Mycobacterium marinum causes “swimming pool granuloma or fish tank granuloma,” which is a skin lesion at the site of an abrasion acquired in a swimming pool or an aquarium.

(4) Mycobacterium scrofulaceum causes scrofula, which manifests as swollen, nontender cervical lymph nodes (cervical adenitis).

The important rapid grower is Mycobacterium fortuitum-chelonei complex, which causes infections of prosthetic joints and indwelling catheters. It also causes skin and soft tissue infections at the site of puncture wounds. The organisms are usually resistant to most antituberculosis drugs.

Mycobacterium leprae

Disease—Leprosy.

Characteristics—Aerobic, acid-fast rods. Cannot be cultured in vitro. Optimal growth at less than body temperature, so lesions are on cooler parts of the body, such as skin, nose, and superficial nerves.

Habitat and Transmission—Humans are the main reservoir. Also found in armadillos. Most important mode of transmission is nasal secretions of patients with the lepromatous form. Patients with the lepromatous form are more likely to transmit than those with the tuberculoid form because they have much higher numbers of organisms than those with tuberculoid leprosy. Prolonged exposure is usually necessary.

Pathogenesis—Lesions usually occur in the cooler parts of the body (e.g., skin and peripheral nerves). In tuberculoid leprosy, destructive lesions are due to the cell-mediated response to the organism. Damage to fingers is due to burns and other trauma, because nerve damage causes loss of sensation. In lepromatous leprosy, the cell-mediated response to M. leprae is lost, and large numbers of organisms appear in the lesions and blood. No toxins or virulence factors are known.

Laboratory Diagnosis—Acid-fast rods are abundant in lepromatous leprosy, but few are found in the tuberculoid form. Cultures and serologic tests not done. Lepromin skin test is positive in the tuberculoid but not in the lepromatous form. A serologic test for IgM against phenolic glycolipid-1 is useful in the diagnosis of lepromatous leprosy.

Treatment—Dapsone plus rifampin for the tuberculoid form. Clofazimine is added to that regimen for the lepromatous form or if the organism is resistant to dapsone. Treatment is for at least 2 years.

Prevention—Dapsone for close family contacts. No vaccine is available.

ACTINOMYCETES (CHAPTER 22)

Actinomyces israelii

Disease—Actinomycosis (abscesses with draining sinus tracts).

Characteristics—Anaerobic, gram-positive filamentous, branching rods.

Habitat and Transmission—Habitat is human mouth, especially anaerobic crevices around the teeth. Transmission into tissues occurs during dental disease or trauma. Organism also aspirated into lungs, causing thoracic actinomycosis. Retained intrauterine device (IUD) predisposes to pelvic actinomycosis.

Pathogenesis—No toxins or virulence factors known. Organism forms sinus tracts that open onto skin and contain “sulfur granules,” which are mats of intertwined filaments of bacteria.

Laboratory Diagnosis—Gram-stained smear plus anaerobic culture on blood agar plate. “Sulfur granules” visible in the pus. No serologic tests.

Treatment—Penicillin G and surgical drainage.

Prevention—No vaccine or drug is available.

Nocardia asteroides

Disease—Nocardiosis (especially lung and brain abscesses).

Characteristics—Aerobic, gram-positive filamentous, branching rods. Weakly acid-fast.

Habitat and Transmission—Habitat is the soil. Transmission is via airborne particles, which are inhaled into the lungs.

Pathogenesis—No toxins or virulence factors known. Immunosuppression and cancer predispose to infection.

Laboratory Diagnosis—Gram-stained smear and modified Ziehl-Neelsen stain. Aerobic culture on blood agar plate. No serologic tests.

Treatment—Sulfonamides.

Prevention—No vaccine or drug is available.

MYCOPLASMAS (CHAPTER 23)

Mycoplasma pneumoniae

Disease—“Atypical” pneumonia.

Characteristics—Smallest free-living organisms. Not seen on Gram-stained smear because they have no cell wall, so dyes are not retained. Penicillins and cephalosporins are not effective because there is no cell wall (peptidoglycan). The only bacteria with cholesterol in cell membrane. Can be cultured in vitro.

Habitat and Transmission—Habitat is the human respiratory tract. Transmission is via respiratory droplets.

Pathogenesis—No exotoxins produced. No endotoxin because there is no cell wall. Produces hydrogen peroxide, which may damage the respiratory tract.

Laboratory Diagnosis—Gram stain not useful. Can be cultured on special bacteriologic media but takes at least 10 days to grow, which is too long to be clinically useful. Positive cold–agglutinin test is presumptive evidence. Complement fixation test for antibodies to Mycoplasma pneumoniae is more specific.

Treatment—Azithromycin or doxycycline.

Prevention—No vaccine or drug is available.

SPIROCHETES (CHAPTER 24)

Treponema pallidum

Disease—Syphilis.

Characteristics—Spirochetes. Not seen on Gram-stained smear because organism is too thin. Not cultured in vitro.

Habitat and Transmission—Habitat is the human genital tract. Transmission is by sexual contact and from mother to fetus across the placenta.

Pathogenesis—Organism multiplies at site of inoculation and then spreads widely via the bloodstream. Many features of syphilis are attributed to blood vessel involvement causing vasculitis. Primary (chancre) and secondary lesions heal spontaneously. Tertiary lesions consist of gummas (granulomas in bone, muscle, and skin), aortitis, or central nervous system inflammation. No toxins or virulence factors known.

Laboratory Diagnosis—Seen by dark field microscopy or immunofluorescence. Serologic tests important: VDRL and RPR are nontreponemal (nonspecific) tests used for screening; FTA-ABS is the most widely used specific test for Treponema pallidum. Antigen in VDRLand RPR is beef heart cardiolipin; antigen in FTA-ABS is killed T. pallidum. VDRL declines with treatment, whereas FTA-ABS remains positive for life.

Treatment—Penicillin is effective in the treatment of all stages of syphilis. In primary and secondary syphilis, use benzathine penicillin G (a depot preparation) because T. pallidum grows slowly, so drug must be present for a long time. There is no resistance.

Prevention—Benzathine penicillin given to contacts. No vaccine is available.

Borrelia burgdorferi

Disease—Lyme disease.

Characteristics—Spirochetes. Gram stain not useful. Can be cultured in vitro, but not usually done.

Habitat and Transmission—The main reservoir is the white-footed mouse. Transmitted by the bite of ixodid ticks, especially in three areas in the United States: Northeast (e.g., Connecticut), Midwest (e.g., Wisconsin), and West Coast (e.g., California). Eighty percent of cases are in the northeastern states of Connecticut, New York, and New Jersey. Very small nymph stage of ixodid tick (deer tick) is most common vector. Tick must feed for at least 24 hours to deliver an infectious dose of B. burgdorferi.

Pathogenesis—Organism invades skin, causing a rash called erythema migrans. It then spreads via the bloodstream to involve primarily the heart, joints, and central nervous system. No toxins or virulence factors identified.

Laboratory Diagnosis—Diagnosis usually made serologically (i.e., by detecting IgM antibody). Confirm positive serologic test with Western blot assay.

Treatment—Doxycycline for early stages; penicillin G for late stages.

Prevention—Vaccine containing outer membrane protein of the organism was available but has been withdrawn. Avoid tick bite. Can give doxycycline or amoxicillin to people who are bitten by a tick in endemic areas.

Leptospira interrogans

Disease—Leptospirosis.

Characteristics—Spirochetes that can be seen on dark field microscopy but not light microscopy. Can be cultured in vitro.

Habitat and Transmission—Habitat is wild and domestic animals. Transmission is via animal urine. In the United States, transmission is chiefly via dog, livestock, and rat urine.

Pathogenesis—Two phases: an initial bacteremic phase and a subsequent immunopathologic phase with meningitis. No toxins or virulence factors known.

Laboratory Diagnosis—Dark field microscopy and culture in vitro are available but not usually done. Diagnosis usually made by serologic testing for antibodies in patient’s serum.

Treatment—Penicillin G. There is no significant antibiotic resistance.

Prevention—Doxycycline effective for short-term exposure. Vaccination of domestic livestock and pets. Rat control.

Borrelia recurrentis

Causes relapsing fever. Transmitted by human body louse. Organism well-known for its rapid antigenic changes, which account for the relapsing nature of disease. Antigenic changes are due to programmed rearrangements of bacterial DNA encoding surface proteins.

CHLAMYDIAE (CHAPTER 25)

Chlamydia trachomatis

Diseases—Nongonococcal urethritis, cervicitis, inclusion conjunctivitis, lymphogranuloma venereum, and trachoma. Also pneumonia in infants.

Characteristics—Obligate intracellular parasites. Not seen on Gram-stained smear. Exists as inactive elementary body extracellularly and as metabolically active, dividing reticulate body intracellularly.

Habitat and Transmission—Habitat is the human genital tract and eyes. Transmission is by sexual contact and during passage of neonate through birth canal. Transmission in trachoma is chiefly by hand-to-eye contact.

Pathogenesis—No toxins or virulence factors known.

Laboratory Diagnosis—Nucleic acid amplification test (NAAT) using the patient’s urine is used to diagnose chlamydial sexually transmitted disease. Cytoplasmic inclusions seen on Giemsa-stained or fluorescent antibody–stained smear of exudate. PCR-based assay is available. Organism grows in cell culture and embryonated eggs, but these are not often used.

Treatment—A tetracycline (e.g., doxycycline) or a macrolide (e.g., azithromycin).

Prevention—Erythromycin effective in infected mother to prevent neonatal disease. No vaccine is available.

Chlamydia pneumoniae

Disease—Atypical pneumonia.

Characteristics—Same as C. trachomatis.

Habitat and Transmission—Habitat is human respiratory tract. Transmission is by respiratory aerosol.

Pathogenesis—No toxins or virulence factors known.

Laboratory Diagnosis—Serologic tests for antibody in patient’s serum.

Treatment—A tetracycline, such as doxycycline.

Prevention—No vaccine or drug is available.

Chlamydia psittaci

Disease—Psittacosis.

Characteristics—Same as C. trachomatis.

Habitat and Transmission—Habitat is birds, both psittacine and others. Transmission is via aerosol of dried bird feces.

Pathogenesis—No toxins or virulence factors known.

Laboratory Diagnosis—Diagnosis usually made by testing for antibodies in patient’s serum. Cytoplasmic inclusion seen by Giemsa or fluorescent antibody staining. Organism can be isolated from sputum, but this is rarely done.

Treatment—Tetracycline.

Prevention—No vaccine or drug is available.

RICKETTSIAE (CHAPTER 26)

Rickettsia rickettsii

Disease—Rocky Mountain spotted fever.

Characteristics—Obligate intracellular parasites. Not seen well on Gram-stained smear. Antigens cross-react with OX strains of Proteus vulgaris (Weil-Felix reaction).

Habitat and TransmissionDermacentor (dog) ticks are both the vector and the main reservoir. Transmission is via tick bite. Dogs and rodents can be reservoirs as well.

Pathogenesis—Organism invades endothelial lining of capillaries, causing vasculitis. No toxins or virulence factors identified.

Laboratory Diagnosis—Diagnosis made by detecting antibody in serologic tests such as the ELISA test. Weil-Felix test is no longer used. Stain and culture rarely done.

Treatment—Tetracycline.

Prevention—Protective clothing and prompt removal of ticks. Tetracycline effective in exposed persons. No vaccine is available.

Rickettsia prowazekii

Disease—Typhus.

Characteristics—Same as R. rickettsii.

Habitat and Transmission—Humans are the reservoir, and transmission is via the bite of the human body louse.

Pathogenesis—No toxins or virulence factors known.

Laboratory Diagnosis—Serologic tests for antibody in patient’s serum.

Treatment—A tetracycline, such as doxycycline.

Prevention—A killed vaccine is used in the military but is not available for civilian use.

Coxiella burnetii

Disease—Q fever.

Characteristics—Obligate intracellular parasites. Not seen well on Gram-stained smear.

Habitat and Transmission—Habitat is domestic livestock. Transmission is by inhalation of aerosols of urine, feces, amniotic fluid, or placental tissue. The only rickettsia not transmitted to humans by an arthropod.

Pathogenesis—No toxins or virulence factors known.

Laboratory Diagnosis—Diagnosis usually made by serologic tests. Weil-Felix test is negative. Stain and culture rarely done.

Treatment—Tetracycline.

Prevention—Killed vaccine for persons in high-risk occupations. No drug is available.

MINOR BACTERIAL PATHOGENS (CHAPTER 27)

Only the most important of the minor bacterial pathogens are summarized in this section.

Anaplasma phagocytophilum

Member of Rickettsia family. Causes human granulocytic anaplasmosis. Transmitted from reservoir (rodents, dogs) to humans by ticks, especially Ixodes, the deer tick. Endemic in northeastern and northcentral states (e.g., Connecticut and Wisconsin). Forms morulae in cytoplasm of monocytes. (A morula is a “mulberry-shaped” inclusion body composed of many A. phagocytophilum cells.)

Eikenella corrodens

Gram-negative rod that is a member of the normal flora in the human mouth. It causes skin and bone infections associated with human bites and “clenched fist” injuries.

Ehrlichia chaffeensis

Member of Rickettsia family. Causes human monocytic ehrlichiosis. Transmitted from dog reservoir to humans by ticks, especially Dermacentor, the dog tick. Endemic in southern states (e.g., Arkansas). Forms morulae in cytoplasm of monocytes. (A morula is a “mulberry-shaped” inclusion body composed of many E. chaffeensis cells.)

Fusobacterium nucleatum

Anaerobic gram-negative rod with pointed ends. Member of the normal human flora in mouth, colon, and female genital tract. Causes brain, lung, abdominal, and pelvic abscesses, typically in combination with other anaerobes and facultative bacteria.

Gardnerella vaginalis

Facultative gram-variable rod. Involved in bacterial vaginosis, along with Mobiluncus species, which are anaerobic. See “clue cells,” which are vaginal epithelial cells covered with G. vaginalis cells. Positive “whiff” test found in bacterial vaginosis.

Haemophilus ducreyi

Small gram-negative rod. Causes chancroid. Sexually transmitted disease with painful ulcer on genitals (in contrast to syphilis, which is painless). To grow in culture, it requires factor X (heme) but not factor V (in contrast to H. influenzae, which requires both).

Moraxella catarrhalis

Small coccobacillary gram-negative rod that resembles the cocci of the genus Neisseria. Causes otitis media and sinusitis primarily in children. Also causes bronchitis and pneumonia, primarily in older people with chronic obstructive pulmonary disease. It is found only in humans and is transmitted by respiratory aerosol.

Yersinia enterocolitica

Gram-negative rods. Causes enterocolitis similar to that caused by Shigella and Salmonella. Also causes mesenteric adenitis, which can mimic appendicitis. Found in domestic animals and transmitted to humans by fecal contamination of food.

SUMMARIES OF MEDICALLY IMPORTANT VIRUSES

DNA ENVELOPED VIRUSES (CHAPTER 37)

Herpes Simplex Virus Type 1

Diseases—Herpes labialis (fever blisters or cold sores), keratitis, encephalitis.

Characteristics—Enveloped virus with icosahedral nucleocapsid and linear double-stranded DNA. No virion polymerase. One serotype; cross-reaction with herpes simplex virus (HSV) type 2 occurs. HSV-1 can be distinguished from HSV-2 by using monoclonal antibody against glycoprotein G. No herpes group–specific antigen.

Transmission—By saliva or direct contact with virus from the vesicle.

Pathogenesis—Initial vesicular lesions occur in the mouth or on the face. The virus then travels up the axon and becomes latent in sensory (trigeminal) ganglia. Recurrences occur in skin innervated by affected sensory nerve and are induced by fever, sunlight, stress, etc. Dissemination to internal organs occurs in patients with depressed cell-mediated immunity with life-threatening consequences. HSV-1 encephalitis often affects the temporal lobe.

Laboratory Diagnosis—Virus causes cytopathic effect (CPE) in cell culture. It is identified by antibody neutralization or fluorescent antibody test. Tzanck smear of cells from the base of the vesicle reveals multinucleated giant cells with intranuclear inclusions. These giant cells are not specific for HSV-1; they are seen in the vesicular lesions caused by HSV-2 and varicella-zoster virus as well. A rise in antibody titer can be used to diagnose a primary infection but not recurrences. HSV encephalitis can be diagnosed using a PCR assay to detect HSV-1 DNA in spinal fluid.

Treatment—Acyclovir for encephalitis and disseminated disease. Acyclovir has no effect on the latent state of the virus. Trifluridine or acyclovir for keratitis. Primary infections and localized recurrences are self-limited.

Prevention—Recurrences can be prevented by avoiding the specific inciting agent such as intense sunlight. Acyclovir, valacyclovir, or famciclovir is used to reduce recurrences. No vaccine is available.

Herpes Simplex Virus Type 2

Diseases—Herpes genitalis, aseptic meningitis, and neonatal infection.

Characteristics—Enveloped virus with icosahedral nucleocapsid and linear double-stranded DNA. No virion polymerase. One serotype; cross-reaction with HSV-1 occurs. HSV-2 can be distinguished from HSV-1 by using monoclonal antibody against glycoprotein G. No herpes group–specific antigen.

Transmission—Sexual contact in adults and during passage through the birth canal in neonates.

Pathogenesis—Initial vesicular lesions occur on genitals. The virus then travels up the axon and becomes latent in sensory (lumbar or sacral) ganglion cells. Recurrences are less severe than the primary infection. HSV-2 infections in neonate can be life-threatening because neonates have reduced cell-mediated immunity. Asymptomatic shedding of HSV-2 in the female genital tract is an important contributing factor to neonatal infections.

Laboratory Diagnosis—Virus causes CPE in cell culture. Identify by antibody neutralization or fluorescent antibody test. Tzanck smear reveals multinucleated giant cells but is not specific for HSV-2. A rise in antibody titer can be used to diagnose a primary infection but not recurrences.

Treatment—Acyclovir is useful in the treatment of primary and recurrent genital infections as well as neonatal infections. It has no effect on the latent state.

Prevention—Primary disease can be prevented by protection from exposure to vesicular lesions. Recurrences can be reduced by the long-term use of oral acyclovir, valacyclovir, or famciclovir. Neonatal infection can be prevented by delivering the child by cesarean section if the mother has visible vesicular lesions in the birth canal. There is no vaccine.

Varicella-Zoster Virus

Diseases—Varicella (chickenpox) in children and zoster (shingles) in adults.

Characteristics—Enveloped virus with icosahedral nucleocapsid and linear double-stranded DNA. No virion polymerase. One serotype.

Transmission—Varicella is transmitted primarily by respiratory droplets. Zoster is not transmitted; it is caused by a reactivation of latent virus.

Pathogenesis—Initial infection is in the oropharynx. It spreads via the blood to the internal organs such as the liver and then to the skin. After the acute episode of varicella, the virus remains latent in the sensory ganglia and can reactivate to cause zoster years later, especially in older and immunocompromised individuals.

Laboratory Diagnosis—Virus causes CPE in cell culture and can be identified by fluorescent antibody test. Multinucleated giant cells seen in smears from the base of the vesicle. Intranuclear inclusions seen in infected cells. A fourfold or greater rise in antibody titer in convalescent-phase serum is diagnostic.

Treatment—No antiviral therapy is indicated for varicella or zoster in the immunocompetent patient. In the immunocompromised patient, acyclovir can prevent dissemination.

Prevention—Both the varicella vaccine and the zoster vaccine contain live, attenuated varicella-zoster virus. Immunocompromised patients exposed to the virus should receive passive immunization with varicella-zoster immune globulin (VZIG) and acyclovir to prevent disseminated disease.

Cytomegalovirus

Diseases—Most common cause of congenital abnormalities in the United States. Cytomegalic inclusion body disease in infants. Mononucleosis in transfusion recipients. Pneumonia and hepatitis in immunocompromised patients. Retinitis and enteritis, especially in AIDS patients.

Characteristics—Enveloped virus with icosahedral nucleocapsid and linear double-stranded DNA. No virion polymerase. One serotype.

Transmission—Virus is found in many human body fluids, including blood, saliva, semen, cervical mucus, breast milk, and urine. It is transmitted via these fluids, across the placenta, or by organ transplantation.

Pathogenesis—Initial infection usually in the oropharynx. In fetal infections, the virus spreads to many organs (e.g., central nervous system and kidneys). In adults, lymphocytes are frequently involved. A latent state occurs in monocytes. Disseminated infection in immunocompromised patients can result from either a primary infection or reactivation of a latent infection.

Laboratory Diagnosis—The virus causes CPE in cell culture and can be identified by fluorescent antibody test. “Owl’s eye” nuclear inclusions are seen. A fourfold or greater rise in antibody titer in convalescent-phase serum is diagnostic.

Treatment—Ganciclovir is used to treat pneumonia and retinitis. Acyclovir is ineffective.

Prevention—No vaccine is available. Ganciclovir suppresses retinitis. Do not transfuse CMV antibody-positive blood into newborns or antibody-negative immunocompromised patients.

Epstein–Barr Virus

Disease—Infectious mononucleosis; associated with Burkitt’s lymphoma in East African children.

Characteristics—Enveloped virus with icosahedral nucleocapsid and linear double-stranded DNA. No virion polymerase. One serotype.

Transmission—Virus found in human oropharynx and B lymphocytes. It is transmitted primarily by saliva.

Pathogenesis—In infectious mononucleosis, infection begins in the pharyngeal epithelium, spreads to the cervical lymph nodes, and then travels via the blood to the liver and spleen. EBV establishes latency in B lymphocytes. In Burkitt’s lymphoma, oncogenesis is a function of the translocation of the c-myc oncogene to a site adjacent to an immunoglobulin gene promoter. This enhances synthesis of the c-myc protein, a potent oncoprotein.

Laboratory Diagnosis—The virus is rarely isolated. In infectious mononucleosis, lymphocytosis, including atypical lymphocytes, occurs. Heterophil antibody is typically positive (Monospot test). Heterophil antibody agglutinates sheep or horse red blood cells. A significant rise in EBV-specific antibody to viral capsid antigen is diagnostic.

Treatment—No effective drug is available for infectious mononucleosis.

Prevention—There is no drug or vaccine.

Human Herpesvirus 8

Causes Kaposi’s sarcoma, especially in AIDS patients. Transmitted sexually. Diagnosis made by pathologic examination of lesion biopsy. See spindle cells and extravasated red blood cells. Purple color of lesions due to collections of venous blood. No specific antiviral treatment and no vaccine.

Smallpox Virus

Disease—Smallpox. The disease smallpox has been eradicated by use of the vaccine. The last known case was in 1977 in Somalia.

Characteristics—Poxviruses are the largest viruses. Enveloped virus with linear double-stranded DNA. DNA-dependent RNA polymerase in virion. One serologic type.

Transmission—By respiratory droplets or direct contact with the virus from skin lesions.

Pathogenesis—The virus infects the mucosal cells of the upper respiratory tract, then spreads to the local lymph nodes and by viremia to the liver and spleen and later the skin. Skin lesions progress in the following order: macule, papule, vesicle, pustule, crust.

Laboratory Diagnosis—Virus identified by CPE in cell culture or “pocks” on chorioallantoic membrane. Electron microscopy reveals typical particles; cytoplasmic inclusions seen in light microscopy. Viral antigens in the vesicle fluid can be detected by precipitin tests. A fourfold or greater rise in antibody titer in the convalescent-phase serum is diagnostic.

Treatment—None.

Prevention—Vaccine contains live, attenuated vaccinia virus. Vaccine is no longer used except by the military, because the disease has been eradicated.

Molluscum Contagiosum Virus

Causes molluscum contagiosum. See pinkish, papular skin lesions with an umbilicated center. Lesions usually on the face, especially around the eyes. Transmitted by direct contact. Diagnosis made clinically; laboratory is not involved. There is no established antiviral therapy and no vaccine. Cidofovir may be useful in the treatment of the extensive lesions that occur in immunocompromised patients.

DNA NONENVELOPED VIRUSES (CHAPTER 38)

Adenovirus

Diseases—Upper and lower tract respiratory disease, especially pharyngitis and pneumonia. Also conjunctivitis (pink-eye). Enteric strains cause diarrhea. Some strains cause sarcomas in certain animals but not humans.

Characteristics—Nonenveloped virus with icosahedral nucleocapsid and linear double-stranded DNA. No virion polymerase. There are 41 serotypes, some associated with specific diseases.

Transmission—Respiratory droplet primarily; iatrogenic transmission in eye disease; fecal–oral transmission with enteric strains.

Pathogenesis—Virus preferentially infects epithelium of respiratory tract and eyes. After acute infection, persistent, low-grade virus production without symptoms can occur in the pharynx.

Laboratory Diagnosis—Virus causes CPE in cell culture and can be identified by fluorescent antibody or complement fixation test. Antibody titer rise in convalescent-phase serum is diagnostic.

Treatment—None.

Prevention—Live vaccine against types 3, 4, and 7 is used in the military to prevent pneumonia.

Human Papillomavirus

Diseases—Papillomas (warts); condylomata acuminata (genital warts); associated with carcinoma of the cervix and penis.

Characteristics—Nonenveloped virus with icosahedral nucleocapsid and circular double-stranded DNA. No virion polymerase. There are at least 60 types, which are determined by DNA sequence not by antigenicity. Many types infect the epithelium and cause papillomas at specific body sites.

Transmission—Direct contact of skin or genital lesions.

Pathogenesis—Two early viral genes, E6 and E7, encode proteins that inhibit the activity of proteins encoded by tumor suppressor genes (e.g., the p53 gene and the retinoblastoma gene, respectively).

Laboratory Diagnosis—Diagnosis is made clinically by finding koilocytes in the lesions. DNA hybridization tests are available. Virus isolation and serologic tests are not done.

Treatment—Podophyllin or liquid nitrogen are most commonly used. Alpha interferon is also available.

Prevention—Two vaccines are available: one contains the capsid proteins of four HPV types (6, 11, 16 and 18) and the other contains the capsid proteins of two types (16 and 18). Treatment varies according to the site of lesions: liquid nitrogen is used for skin lesions, podophyllin for genital lesions, and salicylic acid for plantar lesions.

Parvovirus B19

Diseases—Slapped cheek syndrome (erythema infectiosum), aplastic anemia, arthritis, and hydrops fetalis.

Characteristics—Nonenveloped virus with icosahedral symmetry and single-stranded DNA genome. Virion contains no polymerase. There is one serotype.

Transmission—Respiratory droplets and transplacental.

Pathogenesis—Virus preferentially infects erythroblasts, causing aplastic anemia in patients with hereditary anemias; immune complexes cause rash and arthritis. Virus can infect fetus and cause severe anemia, leading to congestive heart failure and edema (hydrops fetalis). Maternal antibody protects fetus from infection.

Laboratory Diagnosis—Serologic tests.

Treatment—None.

Prevention—There is no drug or vaccine.

RNA ENVELOPED VIRUSES (CHAPTER 39)

Influenza Virus

Disease—Influenza. Influenza A virus is the main cause of worldwide epidemics (pandemics). A pandemic caused by a swine-origin strain of H1N1 influenza A virus began in 2009.

Characteristics—Enveloped virus with a helical nucleocapsid and segmented, single-stranded RNA of negative polarity. RNA polymerase in virion. The two major antigens are the hemagglutinin (HA) and the neuraminidase (NA) on separate surface spikes. Antigenic shift in these proteins as a result of reassortment of RNA segments accounts for the epidemics of influenza caused by influenza A virus. Influenza A viruses of animals are the source of the new RNA segments. Antigenic drift due to mutations also contributes. The virus has many serotypes because of these antigenic shifts and drifts. The antigenicity of the internal nucleocapsid protein determines whether the virus is an A, B, or C influenza virus.

Transmission—Respiratory droplets from human to human. H5N1 strains transmitted from birds to humans.

Pathogenesis—Infection is limited primarily to the epithelium of the respiratory tract.

Laboratory Diagnosis—A rapid ELISA test to detect influenza viral antigen in respiratory secretions is often used. Virus grows in cell culture and embryonated eggs and can be detected by hemadsorption or hemagglutination. It is identified by hemagglutination inhibition or complement fixation. A fourfold or greater antibody titer rise in convalescent-phase serum is diagnostic.

Treatment—The neuraminidase inhibitor, oseltamivir (Tamiflu), is the drug of choice. Zanamivir, another neuraminidase inhibitor, is also available. Amantadine and rimantadine are no longer used due to widespread resistance.

Prevention—Two types of vaccines are available: (1) a killed (subunit) vaccine containing purified HA and NA; and (2) a vaccine containing a live, temperature-sensitive mutant of influenza virus. The virus in the live vaccine replicates in cool nasal passages, where it induces secretory IgA, but not in warm lower respiratory tract. Both vaccines contain the strains of influenza A and B virus currently causing disease. The killed vaccine is not a good immunogen and must be given annually. The vaccine against “standard” influenza contains either two A strains (H1N1 and H3N2) and one B strain or those two A strains and two B strains. The vaccine against “swine” influenza contains only the novel H1N1 strain of swine origin. Most of these vaccines are made in eggs, so anyone who has had a severe anaphylactic response to egg proteins should not receive the egg-derived vaccine. In 2013, a vaccine not made in eggs became available. Oseltamivir (Tamiflu) can be used for prophylaxis in unimmunized people who have been exposed.

Measles Virus

Disease—Measles. Subacute sclerosing panencephalitis is a rare late complication.

Characteristics—Enveloped virus with a helical nucleocapsid and one piece of single-stranded, negative-polarity RNA. RNA polymerase in virion. It has a single serotype.

Transmission—Respiratory droplets.

Pathogenesis—Initial site of infection is the upper respiratory tract. Virus spreads to local lymph nodes and then via the blood to other organs, including the skin. Giant cell pneumonia and encephalitis can occur. The maculopapular rash is due to cell-mediated immune attack by cytotoxic T cells on virus-infected vascular endothelial cells in the skin.

Laboratory Diagnosis—The virus is rarely isolated. Serologic tests are used if necessary. PCR assay is available.

Treatment—No antiviral therapy is available.

Prevention—Vaccine contains live, attenuated virus. Usually given in combination with mumps and rubella vaccines.

Mumps Virus

Disease—Mumps. Sterility due to bilateral orchitis is a rare complication.

Characteristics—Enveloped virus with a helical nucleocapsid and one piece of single-stranded, negative-polarity RNA. RNA polymerase in virion. It has a single serotype.

Transmission—Respiratory droplets.

Pathogenesis—The initial site of infection is the upper respiratory tract. The virus spreads to local lymph nodes and then via the bloodstream to other organs, especially the parotid glands, testes, ovaries, meninges, and pancreas.

Laboratory Diagnosis—The virus can be isolated in cell culture and detected by hemadsorption. Diagnosis can also be made serologically. PCR assay is available.

Treatment—No antiviral therapy is available.

Prevention—Vaccine contains live, attenuated virus. Usually given in combination with measles and rubella vaccines.

Rubella Virus

Disease—Rubella. Congenital rubella syndrome is characterized by congenital malformations, especially affecting the cardiovascular and central nervous systems, and by prolonged virus excretion. The incidence of congenital rubella has been greatly reduced by the widespread use of the vaccine.

Characteristics—Enveloped virus with an icosahedral nucleocapsid and one piece of single-stranded positive-polarity RNA. No polymerase in virion. It has a single serotype.

Transmission—Respiratory droplets and across the placenta from mother to fetus.

Pathogenesis—The initial site of infection is the nasopharynx, from which it spreads to local lymph nodes. It then disseminates to the skin via the bloodstream. The rash is attributed to both viral replication and immune injury. During maternal infection, the virus replicates in the placenta and then spreads to fetal tissue. If infection occurs during the first trimester, a high frequency of congenital malformations occurs. Maternal antibody protects against fetal infection.

Laboratory Diagnosis—Virus is detected by PCR assay. To determine whether an adult woman is immune, a single serum specimen to detect IgG antibody in the hemagglutination inhibition test is used. To detect whether recent infection has occurred, either a single serum specimen for IgM antibody or a set of acute-and convalescent-phase sera for IgG antibody can be used.

Treatment—No antiviral therapy is available.

Prevention—Vaccine contains live, attenuated virus. Usually given in combination with measles and mumps vaccine.

Parainfluenza Virus

Disease—Bronchiolitis in infants, croup in young children, and the common cold in adults.

Characteristics—Enveloped virus with helical nucleocapsid and one piece of single-stranded, negative-polarity RNA. RNA polymerase in virion. Unlike influenza viruses, the antigenicity of its hemagglutinin and neuraminidase is stable. There are four serotypes.

Transmission—Respiratory droplets.

Pathogenesis—Infection and death of respiratory epithelium without systemic spread of the virus.

Laboratory Diagnosis—Isolation of the virus in cell culture is detected by hemadsorption. Immunofluorescence is used for identification. A fourfold or greater rise in antibody titer can also be used for diagnosis. PCR assay is available.

Treatment—None.

Prevention—No vaccine or drug is available.

Respiratory Syncytial Virus

Diseases—Most important cause of bronchiolitis and pneumonia in infants. Also causes otitis media in older children.

Characteristics—Enveloped virus with a helical nucleocapsid and one piece of single-stranded, negative-polarity RNA. RNA polymerase in virion. Unlike other paramyxoviruses, it has only a fusion protein in its surface spikes. It has no hemagglutinin. It has two serotypes.

Transmission—Respiratory droplets.

Pathogenesis—Infection involves primarily the lower respiratory tract in infants without systemic spread. Immune response probably contributes to pathogenesis. Multinucleated giant cells caused by the viral fusion protein are a hallmark.

Laboratory Diagnosis—Enzyme immunoassay (rapid antigen test) detects respiratory syncytial virus (RSV) antigens in respiratory secretions. Isolation in cell culture. Multinucleated giant cells visible. Immunofluorescence is used for identification. Serology is not useful for diagnosis in infants. PCR assay is available.

Treatment—Aerosolized ribavirin for very sick infants.

Prevention—Passive immunization with palivizumab (monoclonal antibody) or immune globulins in infants who have been exposed is effective. Handwashing and the use of gloves may prevent nosocomial outbreaks in the newborn nursery.

Coronavirus

Disease—Common cold and SARS (severe acute respiratory syndrome).

Characteristics—Enveloped virus with helical nucleocapsid and one piece of single-stranded, positive-polarity RNA. No virion polymerase. There are two serotypes.

Transmission—Respiratory droplets. Animal coronaviruses may be the source of human infection.

Pathogenesis—Infection is typically limited to the mucosal cells of the respiratory tract. At least 50% of infections are asymptomatic. Immunity is brief and reinfection occurs.

Laboratory Diagnosis—The diagnosis primarily a clinical one. Antibody-based and PCR-based tests are available but not often done.

Treatment—None.

Prevention—No vaccine or drug available.

Rabies Virus

Disease—Rabies is an encephalitis.

Characteristics—Bullet-shaped enveloped virus with a helical nucleocapsid and one piece of single-stranded, negative-polarity RNA. RNA polymerase in virion. The virus has a single serotype.

Transmission—Main reservoir is wild animals such as skunks, raccoons, and bats. Transmission to humans is usually by animal bite, but the virus is also transmitted by aerosols of bat saliva. In the United States, dogs are infrequently involved because canine immunization is so common, but in developing countries they are often involved.

Pathogenesis—Viral receptor is the acetylcholine receptor. Replication of virus at the site of the bite, followed by axonal transport up the nerve to the central nervous system. After replicating in the brain, the virus migrates peripherally to the salivary glands, where it enters the saliva. When the animal is in the agitated state as a result of encephalitis, virus in the saliva can be transmitted via a bite.

Laboratory Diagnosis—Tissue can be stained with fluorescent antibody or with various dyes to detect cytoplasmic inclusions called Negri bodies. The virus can be grown in cell culture, but the process takes too long to be useful in determining whether a person should receive the vaccine. Serologic testing is useful only to make the diagnosis in the clinically ill patient. Antibody does not form quickly enough to help in the decision whether or not to immunize the person who has been bitten. Serologic testing is also used to evaluate the antibody response to the vaccine given before exposure to those in high-risk occupations. PCR assay can provide rapid diagnosis.

Treatment—No antiviral therapy is available.

Prevention—Preexposure prevention of rabies consists of the vaccine only. Postexposure prevention consists of (1) washing the wound; (2) giving rabies immune globulins (passive immunization), mostly into the wound; and (3) giving the inactivated vaccine (active immunization) made in human cell culture. The decision to give the immune serum and the vaccine depends on the circumstances. Prevention of rabies in dogs and cats by using a killed vaccine has reduced human rabies significantly.

Human T-Cell Lymphotropic Virus

Disease—Adult T-cell leukemia/lymphoma and human T-cell lymphotropic virus (HTLV)-associated myelopathy (also known as tropical spastic paraparesis or chronic progressive myelopathy).

Characteristics—HTLV is a member of the retrovirus family. It causes malignant transformation of CD4-positive T cells (in contrast to human immunodeficiency virus [HIV], which kills those cells). HTLV has three structural genes common to all retroviruses, namely, gag, pol, and env, plus two regulatory genes, tax and rex. The Tax protein is required for malignant transformation. It activates the synthesis of IL-2 (which is T-cell growth factor) and of the IL-2 receptor. IL-2 promotes rapid T-cell growth, which predisposes to malignant transformation.

Transmission—HTLV is transmitted primarily by intravenous drug use, sex, and breast feeding. Transmission by donated blood has greatly decreased in the United States because donated blood that has antibodies to HTLV is discarded. HTLV infection is endemic in certain geographic areas, namely, the Caribbean region including southern Florida, eastern South America, western Africa, and southern Japan.

Pathogenesis—HTLV induces malignant transformation of CD4-positive T lymphocytes by activating IL-2 synthesis as described previously. It also causes HTLV-associated myelopathy (HAM), which is a demyelinating disease of the brain and spinal cord caused either by an autoimmune cross-reaction in which the immune response against HTLV damages the neurons or by cytotoxic T cells that kill HTLV-infected neurons.

Laboratory Diagnosis—Anti-HTLV antibodies can be detected in the patient’s serum using the ELISA test. Western blot assay is used to confirm a positive ELISA result. PCR assay can detect the presence of HTLV RNA or DNA within infected cells.

Treatment and Prevention—No specific antiviral treatment for HTLV infection, and no antiviral drug will cure latent infections by HTLV. No vaccine against HTLV. Preventive measures include discarding donated blood if anti-HTLV antibodies are present, using condoms to prevent sexual transmission, and encouraging women with HTLV antibodies to refrain from breast feeding.

RNA NONENVELOPED VIRUSES (CHAPTER 40)

Poliovirus

Diseases—Paralytic poliomyelitis and aseptic meningitis. Poliomyelitis has been eradicated in the Western Hemisphere and in many other countries.

Characteristics—Naked nucleocapsid virus with single-stranded, positive-polarity RNA. Genome RNA acts as mRNA and is translated into one large polypeptide, which is cleaved by virus-encoded protease to form functional viral proteins. No virion polymerase. There are three serotypes.

Transmission—Fecal–oral route. Humans are the natural reservoir.

Pathogenesis—The virus replicates in the pharynx and the GI tract. It can spread to the local lymph nodes and then through the bloodstream to the central nervous system. Most infections are asymptomatic or very mild. Aseptic meningitis is more frequent than paralytic polio. Paralysis is the result of death of motor neurons, especially anterior horn cells in the spinal cord. Pathogenesis of postpolio syndrome is unknown.

Laboratory Diagnosis—Recovery of the virus from spinal fluid indicates infection of the central nervous system. Isolation of the virus from stools indicates infection but not necessarily disease. It can be found in the GI tract of asymptomatic carriers. The virus can be detected in cell culture by CPE and identified by neutralization with type-specific antiserum. A significant rise in antibody titer in convalescent-phase serum is also diagnostic.

Treatment—No antiviral therapy is available.

Prevention—Disease can be prevented by both the inactivated (Salk) vaccine and the live, attenuated (Sabin) vaccine; both induce humoral antibody that neutralizes the virus in the bloodstream. However, only the oral vaccine induces intestinal IgA, which interrupts the chain of transmission by preventing GI tract infection. For that reason and because it induces immunity of longer duration and is orally administered rather than injected, the Sabin vaccine has been the preferred vaccine for many years. However, there have been a few vaccine-associated cases of paralytic polio caused by poliovirus in the vaccine that reverted to virulence. In view of this, the current recommendation in the United States is to use the killed vaccine.

Coxsackie Viruses

Diseases—Aseptic meningitis, herpangina, pleurodynia, myocarditis, pericarditis, and hand, foot, and mouth disease are the most important diseases. Also Coxsackie virus B4 may cause juvenile diabetes, as it will do so in mice.

Characteristics—Naked nucleocapsid virus with single-stranded, positive-polarity RNA. No virion polymerase. Group A and B viruses are defined by their different pathogenicity in mice. There are multiple serotypes in each group.

Transmission—Fecal–oral route.

Pathogenesis—The initial site of infection is the oropharynx, but the main site is the GI tract. The virus spreads through the bloodstream to various organs.

Laboratory Diagnosis—The virus can be detected by CPE in cell culture and identified by neutralization. A significant rise in antibody titer in convalescent-phase serum is diagnostic.

Treatment—No antiviral therapy is available.

Prevention—No vaccine is available.

Rhinoviruses

Disease—Common cold.

Characteristics—Naked nucleocapsid viruses with single-stranded, positive-polarity RNA. No virion polymerase. There are more than 100 serotypes, which explains why the common cold is so common. Rhinoviruses are destroyed by stomach acid and therefore do not replicate in the GI tract, in contrast to other picornaviruses such as poliovirus, Coxsackie virus, and echovirus, which are resistant to stomach acid.

Transmission—Aerosol droplets and hand-to-nose contact.

Pathogenesis—Infection is limited to the mucosa of the upper respiratory tract and conjunctiva. The virus replicates best at the low temperatures of the nose and less well at 37°C, which explains its failure to infect the lower respiratory tract.

Laboratory Diagnosis—Laboratory tests are rarely used clinically. The virus can be recovered from nose or throat washings by growth in cell culture. Serologic tests are not useful.

Treatment—No antiviral therapy is available.

Prevention—No vaccine is available because there are too many serotypes.

Norovirus

Disease—Gastroenteritis (watery diarrhea).

Characteristics—Nonenveloped virus with icosahedral nucleocapsid and one piece of single-stranded, positive-polarity RNA. No virion polymerase. Many serotypes; exact number is uncertain.

Transmission—Fecal–oral route.

Pathogenesis—Infection is typically limited to the mucosal cells of the intestinal tract. Many infections are asymptomatic. Immunity is brief and reinfection occurs.

Laboratory Diagnosis—The diagnosis primarily a clinical one. A PCR-based test is available but not often done.

Treatment—No antiviral drugs available. Treat diarrhea with fluid and electrolytes.

Prevention—No vaccine or drug available. Handwashing and disinfection of surfaces are helpful.

Rotavirus

Disease—Rotavirus causes gastroenteritis (diarrhea), especially in young children.

Characteristics—Naked double-layered capsid with 11 segments of double-stranded RNA. RNA polymerase in virion. Rotavirus is resistant to stomach acid and hence can reach the small intestine. There are at least six serotypes.

Transmission—Rotavirus is transmitted by the fecal–oral route.

Pathogenesis—Rotavirus infection is limited to the GI tract, especially the small intestine.

Laboratory Diagnosis—Detection of rotavirus in the stool by ELISA. Isolation of the virus is not done from clinical specimens.

Treatment—No antiviral drug is available.

Prevention—There are two rotavirus vaccines. One is a live attenuated vaccine that contains the single most common rotavirus serotype (G1), and the other is a live reassortant vaccine that contains five rotavirus strains.

HEPATITIS VIRUSES (CHAPTER 41)

Hepatitis A Virus

Disease—Hepatitis A.

Characteristics—Naked nucleocapsid virus with a single-stranded, positive-polarity RNA. No virion polymerase. Virus has a single serotype.

Transmission—Fecal–oral route. In contrast to hepatitis B virus (HBV) and hepatitis C virus (HCV), blood-borne transmission of hepatitis A virus (HAV) is uncommon because viremia is brief and of low titer.

Pathogenesis—The virus replicates in the GI tract and then spreads to the liver during a brief viremic period. The virus is not cytopathic for the hepatocyte. Hepatocellular injury is caused by immune attack by cytotoxic T cells.

Laboratory Diagnosis—The most useful test to diagnose acute infection is IgM antibody. Isolation of the virus from clinical specimens is not done.

Treatment—No antiviral drug is available.

Prevention—Vaccine contains killed virus. Administration of immune globulin during the incubation period can mitigate the disease.

Hepatitis B Virus

Diseases—Hepatitis B; implicated as a cause of hepatocellular carcinoma.

Characteristics—Enveloped virus with incomplete circular double-stranded DNA (i.e., one strand has about one-third missing and the other strand is “nicked” [not covalently bonded]). DNA polymerase in virion. HBV-encoded DNA polymerase acts as a reverse transcriptase by using viral mRNA as the template for the synthesis of progeny genome DNA. There are three important antigens: the surface antigen, the core antigen, and the e antigen. Another protein, HBx, inactivates p53 tumor suppressor protein, a process involved in causing hepatocellular carcinoma. In the patient’s serum, long rods and spherical forms composed solely of HBsAg predominate. HBV has one serotype based on the surface antigen.

Transmission—Transmitted by blood, during birth, and by sexual intercourse.

Pathogenesis—Hepatocellular injury due to immune attack by cytotoxic (CD8) T cells. Chronic carrier state occurs in 5% of adult infections but in 90% of neonatal infections because neonates have poor cytotoxic T-cell activity. Chronic carrier state can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatocellular carcinoma may be related to the integration of part of the viral DNA into hepatocyte DNA and subsequent synthesis of HBx protein. Antigen–antibody complexes cause arthritis, rash, and glomerulonephritis.

Laboratory Diagnosis—HBV has not been grown in cell culture. Three serologic tests are commonly used: surface antigen (HBsAg), surface antibody (HBsAb), and core antibody (HBcAb). Detection of HbsAg for more than 6 months indicates a chronic carrier state. The presence of e antigen indicates a chronic carrier who is making infectious virus. The presence of e antigen is an important indicator of transmissibility. An HBV-infected person who has neither detectable HBs antigen nor HBs antibody is said to be in the “window” phase. Diagnosis of this patient is made by detecting HB core antibody. See Chapter 41 for a discussion of the results of these tests.

Treatment—No treatment is given for acute hepatitis B. For chronic hepatitis B, a reverse transcriptase inhibitor, such as tenofovir or entecavir, can reduce the inflammation associated with chronic hepatitis B but does not cure the carrier state. A combination of tenofovir and emtricitabine is also effective.

Prevention—There are three main approaches: (1) vaccine that contains HBsAg as the immunogen; (2) hyperimmune serum globulins obtained from donors with high titers of HBsAb; and (3) education of chronic carriers regarding precautions. Passive-active immunization using both vaccine and immune globulins can prevent infection in neonates and those with needle-stick injuries.

Hepatitis C Virus

Disease—Hepatitis C; associated with hepatocellular carcinoma. HCV is the most prevalent bloodborne pathogen in the United States.

Characteristics—Enveloped virus with one piece of single-stranded, positive-polarity RNA. No polymerase in virion. HCV has multiple serotypes.

Transmission—Most transmission is perinatal or via blood. Sexual transmission is less common.

Pathogenesis—Hepatocellular injury caused by cytotoxic T cells. HCV replication itself does not kill cells (i.e., does not cause a cytopathic effect). More than 50% of infections result in the chronic carrier state. The chronic carrier state predisposes to chronic hepatitis and to hepatocellular carcinoma.

Laboratory Diagnosis—Serologic testing detects antibody to HCV. A PCR-based assay for “viral load” can be used to evaluate whether active infection is present.

Treatment—Treatment of acute hepatitis C with pegylated interferon alpha significantly reduce the number of patients who become chronic carriers. Treatment of chronic hepatitis C with pegylated interferon alpha plus ribavirin reduces the effects of chronic hepatitis but does not eradicate the carrier state. Addition of a protease inhibitor (e.g., boceprevir or telaprevir) greatly increases effectiveness and can reduce the viral load to undetectable levels. The use of sofosbuvir, an inhibitor of the RNA polymerase of HCV is very effective in the treatment of chronic hepatitis C. ,

Prevention—Posttransfusion hepatitis can be prevented by discarding donated blood if antibody to HCV is detected. There is no vaccine, and hyperimmune globulins are not available.

Hepatitis D Virus

Disease—Hepatitis D (hepatitis delta).

Characteristics—Defective virus that uses hepatitis B surface antigen as its protein coat. Hepatitis D virus (HDV) can replicate only in cells already infected with HBV (i.e., HBV is a helper virus for HDV). Genome is one piece of single-stranded, negative-polarity, circular RNA. No polymerase in virion. HDV has one serotype (because HBV has only one serotype).

Transmission—Transmitted by blood, sexually, and from mother to child.

Pathogenesis—Hepatocellular injury probably caused by cytotoxic T cells. Chronic hepatitis and chronic carrier state occur.

Laboratory Diagnosis—Serologic testing detects either delta antigen or antibody to delta antigen.

Treatment—Pegylated alpha interferon mitigates symptoms but does not eradicate the carrier state.

Prevention—Prevention of HBV infection by using the HBV vaccine and the HBV hyperimmune globulins will prevent HDV infection also.

Hepatitis E Virus

Causes outbreaks of hepatitis, primarily in developing countries. Similar to hepatitis A virus in the following ways: transmitted by fecal–oral route, no chronic carrier state, no cirrhosis, and no hepatocellular carcinoma. No antiviral therapy and no vaccine.

ARBOVIRUSES (CHAPTER 42)

All arboviruses are transmitted by arthropods (arthropod-borne) such as mosquitoes and ticks from the wild animal reservoir to humans.

West Nile Virus

Disease—Encephalitis. Most infections are asymptomatic.

Characteristics—Enveloped virus with icosahedral nucleocapsid and single-stranded, positive-polarity RNA. No polymerase in virion.

Transmission—Bite of Culex mosquito. Wild birds are reservoir. Humans are dead-end hosts.

Pathogenesis—Virus transmitted via blood from bite site to brain.

Laboratory Diagnosis—Virus isolation from blood, spinal fluid, or brain. Also antibodies in patient’s serum. PCR test is available.

Treatment—No antiviral treatment.

Prevention—No vaccine or drug is available. Blood for transfusion is screened for antibodies.

Eastern Equine Encephalitis Virus

Member of the togavirus family. Causes encephalitis along the East Coast of the United States. Encephalitis is severe but uncommon. Transmitted to humans (and horses) by mosquitoes from small wild birds, such as sparrows. Humans and horses are “dead-end” hosts because viremia is low. There is no antiviral therapy and no vaccine for humans.

Western Equine Encephalitis Virus, St. Louis Encephalitis Virus, and California Encephalitis Virus

The transmission of these encephalitis viruses is similar (i.e., they are transmitted to humans by mosquitoes from small wild birds). However, they differ in details (i.e., they belong to different virus families and cause disease in different geographic areas). Please consult Chapter 42 in the text for specific information.

Yellow Fever Virus

Member of the flavivirus family. Causes yellow fever in the tropical areas of Africa and South America. “Jungle” yellow fever is transmitted from monkeys to humans by mosquitoes. “Urban” yellow fever is transmitted from human to human by Aedes mosquitoes (i.e., humans are the reservoir in the urban form). Humans are not a “dead-end” host because viremia is high. There is no antiviral therapy. There is a live, attenuated vaccine for humans.

Dengue Virus

Member of the flavivirus family. Causes dengue fever in the Caribbean region and other tropical areas. Dengue is the most common insect-borne viral disease in the world. Transmitted by Aedes mosquitoes from one human to another. A monkey reservoir is suspected. Second episodes may result in dengue hemorrhagic fever, a life-threatening complication. There is no antiviral therapy and no vaccine for humans.

TUMOR VIRUSES (CHAPTER 43)

A. Human Cancer Viruses with RNA Genome

Human T-Cell Lymphotropic Virus

HTLV causes adult T-cell leukemia. Oncogenesis is a function of the tax gene of HTLV. The Tax protein activates synthesis of IL-2, also known as T-cell growth factor, and the receptor for IL-2. For further information, see summary of HTLV in Chapter 39, “RNA Enveloped Viruses.”

Hepatitis C Virus

HCV causes hepatocellular carcinoma in chronic carriers of HCV. The mechanism of oncogenesis by HCV is unclear. It appears to be a consequence of the rapid cell division that occurs in an effort to replace the killed hepatocytes. An oncogene has not been identified in the HCV genome. For further information, see summary of HCV in Chapter 41, “Hepatitis Viruses.”

B. Human Cancer Viruses with DNA Genome

Human Papillomavirus

HPV primarily causes carcinoma of the cervix, penis, and anus. Oncogenesis is a function of the E6 and E7 genes of HPV. The E6 and E7 proteins inactivate the tumor suppressor proteins, p53 and RB, respectively. For further information, see summary of HPV in Chapter 38, “DNA Nonenveloped Viruses.”

Epstein–Barr Virus

EBV primarily causes Burkitt’s lymphoma and nasopharyngeal carcinoma. Oncogenesis is a function of the translocation of the c-myc oncogene to a site adjacent to an immunoglobulin gene promoter. This enhances synthesis of the c-myc protein, a potent oncoprotein. For further information, see summary of EBV in Chapter 37, “DNA Enveloped Viruses.”

Human Herpesvirus 8

Human herpesvirus 8 (HHV-8) causes Kaposi’s sarcoma. Oncogenesis is primarily a function of an early protein analogous to the E7 protein of HPV that inactivates the tumor suppressor protein RB. For further information, see summary of HHV-8 in Chapter 37, “DNA Enveloped Viruses.”

Hepatitis B Virus

HBV causes hepatocellular carcinoma in chronic carriers of HBV. Oncogenesis is primarily a function of the Hbx protein that inactivates the tumor suppressor protein p53. For further information, see summary of HBV in Chapter 41, “Hepatitis Viruses.”

Merkel Cell Polyomavirus

Merkel cell polyomavirus (MCPV) causes carcinoma of Merkel cells in the skin, often on sun-exposed areas such as the face and neck. MCPV is a nonenveloped virus with a double-stranded DNA genome. The T antigen protein of MCPV inhibits tumor suppressor proteins, p53 and RB. Infection with MCPV is widespread, but the carcinoma is rare. The carcinoma cells do not produce virus, so transmission from patients with the carcinoma to others does not occur. Diagnosis is made by microscopic analysis of surgical specimens. There is no virus-based assay. There is no antiviral drug or vaccine.

SLOW VIRUSES & PRIONS (CHAPTER 44)

JC Virus

Member of the papovavirus family. Causes progressive multifocal leukoencephalopathy (PML). Infection with JC virus is widespread, but PML occurs only in immunocompromised patients, such as those with AIDS. Invariably fatal. No antiviral therapy and no vaccine.

Prions

Diseases—Creutzfeldt-Jakob disease (CJD), variant CJD, and kuru. These are transmissible spongiform encephalopathies. There is a hereditary form of CJD called Gerstmann-Sträussler-Scheinker (GSS) syndrome.

Characteristics—Prions are composed of protein only. They have no detectable nucleic acid and are highly resistant to ultraviolet (UV) light, formaldehyde, and heat. They are encoded by a cellular gene. The pathogenic form increases in amount by inducing conformational change in normal form. Normal conformation is alpha helix; abnormal is beta-pleated sheet. In GSS syndrome, a mutation occurs that enhances the probability of the conformational change to the beta-pleated sheet form.

Transmission—In most cases of CJD, mode of transmission is unknown. CJD has been transmitted by pituitary extracts, brain electrodes, and corneal transplants. Kuru was transmitted by ingestion or inoculation of human brain tissue. Variant CJD probably is transmitted by ingestion of cow brain tissue in undercooked food.

Pathogenesis—Aggregation of prion filaments within neurons occurs and vacuoles within neurons cause spongiform changes in brain. No inflammation or immune response occurs.

Laboratory Diagnosis—Brain biopsy shows spongiform changes. No serologic tests are useful. Prions cannot be grown in culture.

Treatment—None.

Prevention—There is no drug or vaccine.

HUMAN IMMUNODEFICIENCY VIRUS (CHAPTER 45)

Disease—Acquired immunodeficiency syndrome (AIDS).

Characteristics—Enveloped virus with two copies (diploid) of a single-stranded, positive-polarity RNA genome. RNA-dependent DNA polymerase (reverse transcriptase) makes a DNA copy of the genome, which integrates into host cell DNA. Precursor polypeptides must be cleaved by virus–encoded protease to produce functional viral proteins. The tat gene encodes a protein that activates viral transcription. Antigenicity of the gp120 protein changes rapidly; therefore, there are many serotypes.

Transmission—Transfer of body fluids (e.g., blood and semen). Also transplacental and perinatal transmission.

Pathogenesis—Two receptors are required for HIV to enter cells. One receptor is CD4 protein found primarily on helper T cells. HIV infects and kills helper T cells, which predisposes to opportunistic infections. Other cells bearing CD4 proteins on the surface (e.g., astrocytes) are infected also. The other receptor for HIV is a chemokine receptor such as CCR5. The NEF protein is an important virulence factor. It reduces class I MHC) protein synthesis, thereby reducing the ability of cytotoxic T cells to kill HIV-infected cells. Cytotoxic T cells are the main host defense against HIV.

Laboratory Diagnosis—HIV can be isolated from blood or semen, but this procedure is not routinely available. Diagnosis is usually made by detecting antibody with ELISA as screening test and Western blot as confirmatory test. Determine the “viral load” (i.e., the amount of HIV RNA in the plasma) using PCR-based assays. A high viral load predicts a more rapid progression to AIDS than a low viral load. PCR-based assays can also detect viral RNA in infected cells, which is useful to detect early infections before antibody is detectable.

Treatment—Highly active antiretroviral therapy (HAART) consists of several drugs combined into various regimens. Each regimen has emtricitabine and tenofovir, to which efavirenz, raltegravir, or a combination of two protease inhibitors (either ritonavir plus atazanavir or ritonavir plus darunavir) is added. Clinical improvement occurs, but the virus persists.

Nucleoside analogues, such as zidovudine, lamivudine, emtricitabine, tenofovir, and others inhibit HIV replication by inhibiting reverse transcriptase. Nonnucleoside inhibitors of reverse transcriptase, such as efavirenz, nevirapine, and others, are used also. Protease inhibitors (e.g., indinavir, ritonavir, and others) prevent cleavage of precursor polypeptides. Integrase inhibitors, such as raltegravir, dolutegravir, and elvitegravir, block the integration of HIV DNA into host cell DNA by inhibiting the integrase of HIV. Enfuvirtide, a “fusion inhibitor” that blocks entry of HIV, and maraviroc, which inhibits binding of the gp120 envelope protein of HIV to the cell co-receptor CCR-5, are also useful. Treatment of the opportunistic infection depends on the organism.

Prevention—Screening of blood prior to transfusion for the presence of antibody. “Safe sex,” including the use of condoms. Zidovudine (ZDV, AZT) with or without a protease inhibitor should be given to HIV-infected mothers and their newborns. ZDV, lamivudine and a protease inhibitor should be given after a needle-stick injury. A combination of tenofovir and emtricitabine can be used for preexposure prophylaxis in individuals at high risk of infection. There is no vaccine.

MINOR VIRAL PATHOGENS (CHAPTER 46)

Only the most important of the minor viral pathogens are summarized in this section.

Ebola Virus

Member of the Filovirus family. Causes Ebola hemorrhagic fever, which has a very high mortality rate. Animal reservoir and mode of transmission to humans are unknown. Human-to-human transmission, especially in hospital setting, is by blood and other body fluids. Diagnosis is usually a clinical one, but serologic tests are available. In electron microscope, see long “thread-like” viruses. Culturing the virus is very dangerous and should be done only in special laboratories. There is no antiviral therapy and no vaccine.

Hantavirus (Sin Nombre Virus)

Member of the bunyavirus family. Causes hantavirus pulmonary syndrome. Sin Nombre virus (SNV) is a robovirus (i.e., it is rodent-borne). Deer mice are the reservoir, and the virus is acquired by inhalation of dried urine and feces. Diagnosis is made by detecting viral RNA in lung tissue or by serologic tests. No antiviral therapy and no vaccine.

Japanese Encephalitis Virus

Member of the flavivirus family. Causes outbreaks of encephalitis in Asian countries. Transmitted to humans by mosquitoes from the reservoir hosts, birds and pigs. No antiviral therapy. An inactivated vaccine is available.

SUMMARIES OF MEDICALLY IMPORTANT FUNGI

FUNGI CAUSING CUTANEOUS & SUBCUTANEOUS MYCOSES (CHAPTER 48)

Dermatophytes (e.g., Trichophyton, Microsporum, Epidermophyton species)

Diseases—Dermatophytoses (e.g., tinea capitis, tinea cruris, and tinea pedis).

Characteristics—These fungi are molds that use keratin as a nutritional source. Not dimorphic. Habitat of most dermatophytes that cause human disease is human skin, with the exception of Microsporum canis, which infects dogs and cats also.

Transmission—Direct contact with skin scales.

Pathogenesis—These fungi grow only in the superficial keratinized layer of the skin. They do not invade underlying tissue. The lesions are due to the inflammatory response to the fungi. Frequency of infection is enhanced by moisture and warmth (e.g., inside shoes). An important host defense is provided by the fatty acids produced by sebaceous glands. The “id” reaction is a hypersensitivity response in one skin location (e.g., fingers) to the presence of the organism in another (e.g., feet).

Laboratory Diagnosis—Skin scales should be examined microscopically in a KOH preparation for the presence of hyphae. The organism is identified by the appearance of its mycelium and its asexual spores on Sabouraud’s agar. Serologic tests are not useful.

Skin Test—Trichophyton antigen can be used to determine the competence of a patient’s cell-mediated immunity. Not used for diagnosis of tinea.

Treatment—Topical agents, such as miconazole, clotrimazole, or tolnaftate, are used. Undecylenic acid is effective against tinea pedis. Griseofulvin is the treatment of choice for tinea unguium and tinea capitis.

Prevention—Skin should be kept dry and cool.

Sporothrix schenckii

Disease—Sporotrichosis.

Characteristics—Thermally dimorphic. Mold in the soil, yeast in the body at 37°C. Habitat is soil or vegetation.

Transmission—Mold spores enter skin in puncture wounds caused by rose thorns and other sharp objects in the garden.

Pathogenesis—Local abscess or ulcer with nodules in draining lymphatics.

Laboratory Diagnosis—Cigar-shaped budding yeasts visible in pus. Culture on Sabouraud’s agar shows typical morphology.

Skin Test—None.

Treatment—Itraconazole.

Prevention—Skin should be protected when gardening.

FUNGI CAUSING SYSTEMIC MYCOSES (CHAPTER 49)

Histoplasma capsulatum

Disease—Histoplasmosis.

Characteristics—Thermally dimorphic (i.e., a yeast at body temperature and a mold in the soil at ambient temperature). The mold grows preferentially in soil enriched with bird droppings. Endemic in Ohio and Mississippi River Valley areas.

Transmission—Inhalation of airborne asexual spores (microconidia).

Pathogenesis—Microconidia enter the lung and differentiate into yeast cells. The yeast cells are ingested by alveolar macrophages and multiply within them. An immune response is mounted, and granulomas form. Most infections are contained at this level, but suppression of cell-mediated immunity can lead to disseminated disease.

Laboratory Diagnosis—Sputum or tissue can be examined microscopically and cultured on Sabouraud’s agar. Yeasts visible within macrophages. The presence of tuberculate chlamydospores in culture at 25°C is diagnostic. A rise in antibody titer is useful for diagnosis, but cross-reaction with other fungi (e.g., Coccidioides) occurs.

Skin Test—Histoplasmin, a mycelial extract, is the antigen. Useful for epidemiologic purposes to determine the incidence of infection. A positive result indicates only that infection has occurred; it cannot be used to diagnose active disease. Because skin testing can induce antibodies, serologic tests must be done first.

Treatment—Amphotericin B or itraconazole for disseminated disease; itraconazole for pulmonary disease.

Prevention—No vaccine is available. Itraconazole can be used for chronic suppression in AIDS patients.

Coccidioides immitis

Disease—Coccidioidomycosis.

Characteristics—Thermally dimorphic. At 37°C in the body, it forms spherules containing endospores. At 25°C, either in the soil or on agar in the laboratory, it grows as a mold. The cells at the tip of the hyphae differentiate into asexual spores (arthrospores). Natural habitat is the soil of arid regions (e.g., San Joaquin Valley in California and parts of Arizona and New Mexico).

Transmission—Inhalation of airborne arthrospores.

Pathogenesis—Arthrospores differentiate into spherules in the lungs. Spherules rupture, releasing endospores that form new spherules, thereby disseminating the infection within the body. A cell-mediated immune response contains the infection in most people, but those who have reduced cell-mediated immunity are at high risk for disseminated disease.

Laboratory Diagnosis—Sputum or tissue should be examined microscopically for spherules and cultured on Sabouraud’s agar. A rise in IgM (using precipitin test) antibodies indicates recent infection. A rising titer of IgG antibodies (using complement-fixation test) indicates dissemination; a decreasing titer indicates a response to therapy.

Skin Test—Either coccidioidin, a mycelial extract, or spherulin, an extract of spherules, is the antigen. Useful in determining whether the patient has been infected. A positive test indicates prior infection but not necessarily active disease.

Treatment—Amphotericin B or itraconazole for disseminated disease; ketoconazole for limited pulmonary disease.

Prevention—No vaccine or prophylactic drug is available.

Blastomyces dermatitidis

Disease—Blastomycosis.

Characteristics—Thermally dimorphic. Mold in the soil, yeast in the body at 37°C. The yeast form has a single, broad-based bud and a thick, refractile wall. Natural habitat is rich soil (e.g., near beaver dams), especially in the upper midwestern region of the United States.

Transmission—Inhalation of airborne spores (conidia).

Pathogenesis—Inhaled conidia differentiate into yeasts, which initially cause abscesses followed by formation of granulomas. Dissemination is rare, but when it occurs, skin and bone are most commonly involved.

Laboratory Diagnosis—Sputum or skin lesions examined microscopically for yeasts with a broad-based bud. Culture on Sabouraud’s agar also. Serologic tests are not useful.

Skin Test—Little value.

Treatment—Itraconazole is the drug of choice.

Prevention—No vaccine or prophylactic drug is available.

Paracoccidioides brasiliensis

Disease—Paracoccidioidomycosis.

Characteristics—Thermally dimorphic. Mold in the soil, yeast in the body at 37°C. The yeast form has multiple buds (resembles the steering wheel of a ship).

Transmission—Inhalation of airborne conidia.

Pathogenesis—Inhaled conidia differentiate to the yeast form in lungs. Can disseminate to many organs.

Laboratory Diagnosis—Yeasts with multiple buds visible in pus or tissues. Culture on Sabouraud’s agar shows typical morphology.

Skin Test—Not useful.

Treatment—Itraconazole.

Prevention—No vaccine or prophylactic drug is available.

FUNGI CAUSING OPPORTUNISTIC MYCOSES (CHAPTER 50)

Candida albicans

Diseases—Thrush, disseminated candidiasis, and chronic mucocutaneous candidiasis.

CharacteristicsCandida albicans is a yeast when part of the normal flora of mucous membranes but forms pseudohyphae and hyphae when it invades tissue. The yeast form produces germ tubes when incubated in serum at 37°C. Not thermally dimorphic.

Transmission—Part of the normal flora of skin, mucous membranes, and GI tract. No person-to-person transmission.

Pathogenesis—Opportunistic pathogen. Predisposing factors include reduced cell-mediated immunity, altered skin and mucous membrane, suppression of normal flora, and presence of foreign bodies. Thrush is most common in infants, immunosuppressed patients, and persons receiving antibiotic therapy. Skin lesions occur frequently on moisture-damaged skin. Disseminated infections, such as endocarditis and endophthalmitis, occur in immunosuppressed patients and intravenous drug users. Chronic mucocutaneous candidiasis occurs in children with a T-cell defect in immunity to Candida.

Laboratory Diagnosis—Microscopic examination of tissue reveals yeasts and pseudohyphae. If only yeasts are found, colonization is suggested. The yeast is gram-positive. Forms colonies of yeasts on Sabouraud’s agar. Germ tube formation and production of chlamydospores distinguish C. albicans from virtually all other species of Candida. Serologic tests not useful.

Skin Test—Used to determine competency of cell-mediated immunity rather than to diagnose candidal disease.

Treatment—Skin infections can be treated with topical antifungal agents such as nystatin or clotrimazole. Oral thrush is treated with fluconazole. Esophageal thrush can be treated with caspofungin. Vaginitis can be treated with either intravaginal clotrimazole or oral fluconazole. Disseminated disease can be treated with either amphotericin B or fluconazole. Chronic mucocutaneous candidiasis is treatable with ketoconazole.

Prevention—Predisposing factors should be reduced or eliminated. Oral thrush can be prevented by using clotrimazole troches or nystatin “swish and swallow.” Fluconazole is used to prevent disseminated infection in immunocompromised patients. There is no vaccine.

Cryptococcus neoformans

Disease—Cryptococcosis, especially cryptococcal meningitis.

Characteristics—Heavily encapsulated yeast. Not dimorphic. Habitat is soil, especially where enriched by pigeon droppings.

Transmission—Inhalation of airborne yeast cells.

Pathogenesis—Organisms cause influenza-like syndrome or pneumonia. They spread via the bloodstream to the meninges. Reduced cell-mediated immunity predisposes to severe disease, but some cases of cryptococcal meningitis occur in immunocompetent people who inhale a large dose of organisms.

Laboratory Diagnosis—Visualization of the encapsulated yeast in India ink preparations of spinal fluid. Culture of sputum or spinal fluid on Sabouraud’s agar produces colonies of yeasts. Cryptococcal antigen test (CRAG) is a latex agglutination test that detects polysaccharide capsular antigen in spinal fluid.

Skin Test—Not available.

Treatment—Amphotericin B plus flucytosine for meningitis.

Prevention—Cryptococcal meningitis can be prevented in AIDS patients by using oral fluconazole. There is no vaccine.

Aspergillus fumigatus

Diseases—Invasive aspergillosis is the major disease. Allergic bronchopulmonary aspergillosis and aspergilloma (fungus ball) are important also.

Characteristics—Mold with septate hyphae that branch at a V-shaped angle (low-angle branching). Not dimorphic. Habitat is the soil.

Transmission—Inhalation of airborne spores (conidia).

Pathogenesis—Opportunistic pathogen. In immunocompromised patients, invasive disease occurs. The organism invades blood vessels, causing thrombosis and infarction. A person with a lung cavity (e.g., from tuberculosis) may develop a “fungal ball” (aspergilloma). An allergic (hypersensitive) person (e.g., one with asthma) is predisposed to allergic bronchopulmonary aspergillosis mediated by IgE antibody.

Laboratory Diagnosis—Septate hyphae invading tissue are visible microscopically. Invasion distinguishes disease from colonization. Forms characteristic mycelium when cultured on Sabouraud’s agar. See chains of conidia radiating from a central stalk. Serologic tests detect IgG precipitins in patients with aspergillomas and IgE antibodies in patients with allergic bronchopulmonary aspergillosis.

Skin Test—None available.

Treatment—Amphotericin B or voriconazole for invasive aspergillosis. Some lesions (e.g., fungus balls) can be surgically removed. Corticosteroids plus itraconazole are recommended for allergic bronchopulmonary aspergillosis.

Prevention—No vaccine or prophylactic drug is available.

Mucor & Rhizopus species

Disease—Mucormycosis.

Characteristics—Molds with nonseptate hyphae that typically branch at a 90-degree angle (wide-angle branching). Not dimorphic. Habitat is the soil.

Transmission—Inhalation of airborne spores.

Pathogenesis—Opportunistic pathogens. They cause disease primarily in ketoacidotic diabetic and leukemic patients. The sinuses and surrounding tissue are typically involved. Hyphae invade the mucosa and progress into underlying tissue and vessels, leading to necrosis and infarction.

Laboratory Diagnosis—Microscopic examination of tissue for the presence of nonseptate hyphae that branch at wide angles. Forms characteristic mycelium when cultured on Sabouraud’s agar. See spores contained within a sac called a sporangium. Serologic tests are not available.

Skin Test—None.

Treatment—Amphotericin B and surgical debridement.

Prevention—No vaccine or prophylactic drug is available. Control of underlying disease (e.g., diabetes) tends to prevent mucormycosis.

Pneumocystis jiroveci

Although there is molecular evidence that Pneumocystis jiroveci is a fungus, it is described in these brief summaries in the section on protozoa that cause blood and tissue infections (see page 663).

SUMMARIES OF MEDICALLY IMPORTANT PARASITES

PROTOZOA CAUSING INTESTINAL & UROGENITAL INFECTIONS (CHAPTER 51)

Entamoeba histolytica

Diseases—Amebic dysentery and liver abscess.

Characteristics—Intestinal protozoan. Motile ameba (trophozoite); forms cysts with four nuclei. Life cycle: Humans ingest cysts, which form trophozoites in small intestine. Trophozoites pass to the colon and multiply. Cysts form in the colon, which then pass in the feces.

Transmission and Epidemiology—Fecal–oral transmission of cysts. Human reservoir. Occurs worldwide, especially in tropics.

Pathogenesis—Trophozoites invade colon epithelium and produce flask-shaped ulcer. Can spread to liver and cause amebic abscess.

Laboratory Diagnosis—Trophozoites or cysts visible in stool. Serologic testing (indirect hemagglutination test) positive with invasive (e.g., liver) disease.

Treatment—Metronidazole or tinidazole for symptomatic disease. Iodoquinol or paromomycin for asymptomatic cyst carriers.

Prevention—Proper disposal of human waste. Water purification. Handwashing.

Giardia lamblia

Disease—Giardiasis, especially diarrhea.

Characteristics—Intestinal protozoan. Pear-shaped, flagellated trophozoite, forms cyst with four nuclei. Life cycle: Humans ingest cysts, which form trophozoites in duodenum. Trophozoites form cysts that are passed in feces.

Transmission and Epidemiology—Fecal–oral transmission of cysts. Human and animal reservoir. Occurs worldwide.

Pathogenesis—Trophozoites attach to wall but do not invade. They interfere with absorption of fat and protein.

Laboratory Diagnosis—Trophozoites or cysts visible in stool. String test used if necessary.

Treatment—Metronidazole.

Prevention—Water purification. Handwashing.

Cryptosporidium hominis

Disease—Cryptosporidiosis, especially diarrhea.

Characteristics—Intestinal protozoan. Life cycle: Oocysts release sporozoites; they form trophozoites. After schizonts and merozoites form, microgametes and macrogametes are produced; they unite to form a zygote and then an oocyst.

Transmission and Epidemiology—Fecal–oral transmission of cysts. Human and animal reservoir. Occurs worldwide.

Pathogenesis—Trophozoites attach to wall of small intestine but do not invade.

Laboratory Diagnosis—Oocysts visible in stool with acid-fast stain.

Treatment—No effective therapy; however, paromomycin may reduce symptoms.

Prevention—None.

Trichomonas vaginalis

Disease—Trichomoniasis.

Characteristics—Urogenital protozoan. Pear-shaped, flagellated trophozoites. No cysts or other forms.

Transmission and Epidemiology—Transmitted sexually. Human reservoir. Occurs worldwide.

Pathogenesis—Trophozoites attach to wall of vagina and cause inflammation and discharge.

Laboratory Diagnosis—Trophozoites visible in secretions.

Treatment—Metronidazole for both sexual partners.

Prevention—Condoms limit transmission.

PROTOZOA CAUSING BLOOD & TISSUE INFECTIONS (CHAPTER 52)

Plasmodium species (Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, & Plasmodium falciparum)

Disease—Malaria.

Characteristics—Protozoan that infects red blood cells and tissue (e.g., liver, kidney, and brain). Life cycle: Sexual cycle consists of gametogony (production of gametes) in humans and sporogony (production of sporozoites) in mosquitoes; asexual cycle (schizogony) occurs in humans. Sporozoites in saliva of female Anopheles mosquito enter the human bloodstream and rapidly invade hepatocytes (exoerythrocytic phase). There they multiply and form merozoites (Plasmodium vivax and Plasmodium ovale also form hypnozoites, a latent form). Merozoites leave the hepatocytes and infect red cells (erythrocytic phase). There they form schizonts that release more merozoites, which infect other red cells in a synchronous pattern (3 days for Plasmodium malariae; 2 days for the others). Some merozoites become male and female gametocytes, which, when ingested by female Anopheles, release male and female gametes. These unite to produce a zygote, which forms an oocyst containing many sporozoites. These are released and migrate to salivary glands.

Transmission and Epidemiology—Transmitted by female Anopheles mosquitoes. Occurs primarily in the tropical areas of Asia, Africa, and Latin America.

Pathogenesis—Merozoites destroy red cells, resulting in anemia. Cyclic fever pattern is due to periodic release of merozoites. Plasmodium falciparum can infect red cells of all ages and cause aggregates of red cells that occlude capillaries. This can cause tissue anoxia, especially in the brain (cerebral malaria) and the kidney (blackwater fever). Hypnozoites can cause relapses.

Laboratory Diagnosis—Organisms visible in blood smear. Thick smear is used to detect presence of organism and thin smear to speciate.

Treatment—Chloroquine if sensitive. For chloroquine-resistant P. falciparum, use Coartem or Malarone. Primaquine for hypnozoites of P. vivax and P. ovale. In severe cases, use parenteral artesunate or quinidine.

Prevention—Chloroquine in areas where organisms are sensitive. For those in areas with a high risk of chloroquine resistance, Malarone, mefloquine, or doxycycline. Primaquine to prevent relapses of P. vivax or P. ovale. Protection from bites. Control mosquitoes by using insecticides and by draining water from breeding areas.

Toxoplasma gondii

Disease—Toxoplasmosis, including congenital toxoplasmosis.

Characteristics—Tissue protozoan. Life cycle: Cysts in cat feces or in meat are ingested by humans and differentiate in the gut into forms that invade the gut wall. They infect macrophages and form trophozoites (tachyzoites) that multiply rapidly, kill cells, and infect other cells. Cysts containing bradyzoites form later. Cat ingests cysts in raw meat, and bradyzoites excyst, multiply, and form male and female gametocytes. These fuse to form oocysts in cat gut, which are excreted in cat feces.

Transmission and Epidemiology—Transmitted by ingestion of cysts in raw meat and in food contaminated with cat feces. Also by passage of trophozoites transplacentally from mother to fetus. Infection of fetus occurs only when mother is infected during pregnancy and when she is infected for the first time (i.e., she has no protective antibody). Cat is definitive host; humans and other mammals are intermediate hosts. Occurs worldwide.

Pathogenesis—Trophozoites infect many organs, especially brain, eyes, and liver. Cysts persist in tissue, enlarge, and cause symptoms. Severe disease in patients with deficient cell-mediated immunity (e.g., encephalitis in AIDS patients).

Laboratory Diagnosis—Serologic tests for IgM and IgG antibodies are usually used. Trophozoites or cysts visible in tissue.

Treatment—Sulfadiazine plus pyrimethamine for congenital or disseminated disease.

Prevention—Meat should be cooked. Pregnant women should not handle cats, cat litter boxes, or raw meat. Trimethoprim-sulfamethoxazole is used to prevent Toxoplasma encephalitis in HIV-infected patients.

Pneumocystis jiroveci

Disease—Pneumonia.

Characteristics—Respiratory pathogen. Reclassified in 1988 as a yeast based on molecular evidence but medically has several attributes of a protozoan. Life cycle: uncertain.

Transmission and Epidemiology—Transmitted by inhalation. Humans are reservoir. Occurs worldwide. Most infections asymptomatic.

Pathogenesis—Organisms in alveoli cause inflammation. Immunosuppression predisposes to disease.

Laboratory Diagnosis—Organisms visible in silver stain of lung tissue or lavage fluid.

Treatment—Trimethoprim-sulfamethoxazole is drug of choice. Pentamidine is an alternative drug.

Prevention—Trimethoprim-sulfamethoxazole or aerosolized pentamidine in immunosuppressed individuals.

Trypanosoma cruzi

Disease—Chagas’ disease.

Characteristics—Blood and tissue protozoan. Life cycle: Trypomastigotes in blood of reservoir host are ingested by reduviid bug and form epimastigotes and then trypomastigotes in the gut. When the bug bites, it defecates and feces containing trypomastigotes contaminate the wound. Organisms enter the blood and form amastigotes within cells; these then become trypomastigotes.

Transmission and Epidemiology—Transmitted by reduviid bugs. Humans and many animals are reservoirs. Occurs in rural Latin America.

Pathogenesis—Amastigotes kill cells, especially cardiac muscle, leading to myocarditis. Also neuronal damage, leading to megacolon and megaesophagus.

Laboratory Diagnosis—Trypomastigotes visible in blood, but bone marrow biopsy, culture in vitro, xenodiagnosis, or serologic tests may be required.

Treatment—Nifurtimox or benznidazole for acute disease. No effective drug for chronic disease.

Prevention—Protection from bite. Insect control. Blood for transfusion should not be used if antibodies to T. cruzi are present.

Trypanosoma gambiense & Trypanosoma rhodesiense

Disease—Sleeping sickness (African trypanosomiasis).

Characteristics—Blood and tissue protozoan. Life cycle: Trypomastigotes in blood of human or animal reservoir are ingested by tsetse fly. They differentiate in the gut to form epimastigotes and then metacyclic trypomastigotes in salivary glands. When fly bites, trypomastigotes enter the blood. Repeated variation of surface antigen occurs, which allows the organism to evade the immune response.

Transmission and Epidemiology—Transmitted by tsetse flies. Trypanosoma gambiense has a human reservoir and occurs primarily in west Africa. Trypanosoma rhodesiense has an animal reservoir (especially wild antelope) and occurs primarily in east Africa.

Pathogenesis—Trypomastigotes infect brain, causing encephalitis.

Laboratory Diagnosis—Trypomastigotes visible in blood in early stages and in cerebrospinal fluid in late stages. Serologic tests useful.

Treatment—Suramin in early disease. Suramin plus melarsoprol if central nervous system symptoms exist.

Prevention—Protection from bite. Insect control.

Leishmania donovani

Disease—Kala-azar (visceral leishmaniasis).

Characteristics—Blood and tissue protozoan. Life cycle: Human macrophages containing amastigotes are ingested by sandfly. Amastigotes differentiate in fly gut to promastigotes, which migrate to pharynx. When sandfly bites a human, promastigotes enter blood macrophages and form amastigotes. These can infect other reticuloendothelial cells, especially in spleen and liver.

Transmission and Epidemiology—Transmitted by sandflies (Phlebotomus or Lutzomyia). Animal reservoir (chiefly dogs, small carnivores, and rodents) in Africa, Middle East, and parts of China. Human reservoir in India.

Pathogenesis—Amastigotes kill reticuloendothelial cells, especially in liver, spleen, and bone marrow.

Laboratory Diagnosis—Amastigotes visible in bone marrow smear. Serologic tests useful. Skin test indicates prior infection.

Treatment—Sodium stibogluconate.

Prevention—Protection from bite. Insect control.

Leishmania tropica, Leishmania mexicana, and Leishmania braziliensis

L. tropica and L. mexicana cause cutaneous leishmaniasis; L. braziliensis causes mucocutaneous leishmaniasis. L. tropica occurs primarily in the Middle East, Asia, and India, whereas L. mexicana and L. braziliensis occur in Central and South America. All are transmitted by sandflies. Forest rodents are the main reservoir. Diagnosis is made by observing amastigotes in smear of skin lesion. Treatment is sodium stibogluconate. No specific means of prevention.

MINOR PROTOZOAN PATHOGENS (CHAPTER 53)

Acanthamoeba castellanii

Ameba that causes meningoencephalitis. Also causes keratitis in contact lens wearers. Life cycle includes trophozoite and cyst stages. Found in freshwater lakes and soil. Transmitted via trauma to skin or eyes. Disease occurs primarily in immunocompromised patients. Diagnosis made by finding ameba in spinal fluid. Treatment with pentamidine, ketoconazole, or flucytosine may be effective. No specific means of prevention.

Naegleria fowleri

Ameba that causes meningoencephalitis. Found in freshwater lakes and soil. Life cycle includes trophozoite and cyst stages. Transmitted while swimming or diving in contaminated lake. Disease occurs primarily in healthy individuals. Diagnosis made by finding ameba in spinal fluid. Treatment with amphotericin B may be effective. No specific means of prevention.

Babesia microti

Sporozoan that causes babesiosis. Endemic in rodents along the northeast coast of the United States. Transmitted by Ixodes ticks to humans. Infects red blood cells, causing them to lyse, and anemia results. Asplenic patients have severe disease. Diagnosis is made by observing organism in “Maltese cross” tetrad pattern in red blood cells. Treat with combination of atovaquone and azithromycin for mild disease. Use a combination of quinine and clindamycin for serious disease. No specific means of prevention.

Balantidium coli

Only ciliated protozoan to cause human disease. Causes diarrhea. Acquired by fecal–oral transmission from domestic animals, especially pigs. Diagnosis is made by finding trophozoites or cysts in feces. Treat with tetracycline. No specific means of prevention.

Cyclospora cayetanensis

Coccidian protozoan. Causes diarrhea, especially in immunocompromised (e.g., AIDS) patients. Acquired by fecal–oral transmission. No evidence for animal reservoir. Diagnosis is made by finding oocytes in acid-fast stain of feces. Treat with trimethoprim-sulfamethoxazole. No specific means of prevention.

Isospora belli

Coccidian protozoan. Causes diarrhea, especially in immunocompromised (e.g., AIDS) patients. Acquired by fecal–oral transmission from either human or animal sources. Diagnosis is made by finding oocytes in acid-fast stain of feces. Treat with trimethoprim-sulfamethoxazole. No specific means of prevention.

Microsporidia

Group of spore-forming, obligate intracellular protozoa. Two important species are Enterocytozoon bieneusi and Septata intestinalis. Cause diarrhea, especially in immunocompromised (e.g., AIDS) patients. Acquired by fecal–oral transmission from human sources. Diagnosis is made by finding spores within cells in feces or intestinal biopsy specimens. Treat with albendazole. No specific means of prevention.

CESTODES (CHAPTER 54)

Diphyllobothrium latum

Disease—Diphyllobothriasis.

Characteristics—Cestode (fish tapeworm). Scolex has two elongated sucking grooves; no circular suckers or hooks. Gravid uterus forms a rosette. Oval eggs have an operculum at one end. Life cycle: Humans ingest undercooked fish containing sparganum larvae. Larvae attach to gut wall and become adults containing gravid proglottids. Eggs are passed in feces. In fresh water, eggs hatch and the embryos are eaten by copepods. When these are eaten by freshwater fish, larvae form in the fish muscle.

Transmission and Epidemiology—Transmitted by eating raw or undercooked freshwater fish. Humans are definitive hosts; copepods are the first and fish the second intermediate hosts, respectively. Occurs worldwide but endemic in Scandinavia, Japan, and northcentral United States.

Pathogenesis—Tapeworm in gut causes little damage.

Laboratory Diagnosis—Eggs visible in stool.

Treatment—Praziquantel.

Prevention—Adequate cooking of fish. Proper disposal of human waste.

Echinococcus granulosus

Disease—Hydatid cyst disease.

Characteristics—Cestode (dog tapeworm). Scolex has four suckers and a double circle of hooks. Adult worm has only three proglottids. Life cycle: Dogs are infected when they ingest the entrails of sheep (e.g., liver) containing hydatid cysts. The adult worms develop in the gut, and eggs are passed in the feces. Eggs are ingested by sheep (and humans) and hatch hexacanth larvae in the gut that migrate in the blood to various organs, especially the liver and brain. Larvae form large, unilocular hydatid cysts containing many protoscoleces and daughter cysts.

Transmission and Epidemiology—Transmitted by ingestion of eggs in food contaminated with dog feces. Dogs are main definitive hosts; sheep are intermediate hosts; humans are dead-end hosts. Endemic in sheep-raising areas (e.g., Mediterranean, Middle East, some western states of the United States).

Pathogenesis—Hydatid cyst is a space-occupying lesion. Also, if cyst ruptures, antigens in fluid can cause anaphylaxis.

Laboratory Diagnosis—Serologic tests (e.g., indirect hemagglutination). Pathologic examination of excised cyst.

Treatment—Albendazole or surgical removal of cyst.

Prevention—Sheep entrails should not be fed to dogs.

Taenia saginata

Disease—Taeniasis.

Characteristics—Cestode (beef tapeworm). Scolex has four suckers but no hooks. Gravid proglottids have 15 to 20 uterine branches. Life cycle: Humans ingest undercooked beef containing cysticerci. Larvae attach to gut wall and become adult worms with gravid proglottids. Terminal proglottids detach, pass in feces, and are eaten by cattle. In the gut, oncosphere embryos hatch, burrow into blood vessels, and migrate to skeletal muscles, where they develop into cysticerci.

Transmission and Epidemiology—Transmitted by eating raw or undercooked beef. Humans are definitive hosts; cattle are intermediate hosts. Occurs worldwide but endemic in areas of Asia, Latin America, and Eastern Europe.

Pathogenesis—Tapeworm in gut causes little damage. In contrast to Taenia solium, cysticercosis does not occur.

Laboratory Diagnosis—Gravid proglottids visible in stool. Eggs seen less frequently.

Treatment—Praziquantel.

Prevention—Adequate cooking of beef. Proper disposal of human waste.

Taenia solium

Diseases—Taeniasis and cysticercosis.

Characteristics—Cestode (pork tapeworm). Scolex has four suckers and a circle of hooks. Gravid proglottids have 5 to 10 uterine branches. Life cycle: Humans ingest undercooked pork containing cysticerci. Larvae attach to gut wall and develop into adult worms with gravid proglottids. Terminal proglottids detach, pass in feces, and are eaten by pigs. In gut, oncosphere (hexacanth) embryos burrow into blood vessels and migrate to skeletal muscle, where they develop into cysticerci. If humans eat T. solium eggs in food contaminated with human feces, the oncospheres burrow into blood vessels and disseminate to organs (e.g., brain, eyes), where they encyst to form cysticerci.

Transmission and Epidemiology—Taeniasis acquired by eating raw or undercooked pork. Cysticercosis acquired only by ingesting eggs in fecally contaminated food or water. Humans are definitive hosts; pigs or humans are intermediate hosts. Occurs worldwide but endemic in areas of Asia, Latin America, and southern Europe.

Pathogenesis—Tapeworm in gut causes little damage. Cysticerci can expand and cause symptoms of mass lesions, especially in brain.

Laboratory Diagnosis—Gravid proglottids visible in stool. Eggs seen less frequently.

Treatment—Praziquantel for intestinal worms and for cerebral cysticercosis.

Prevention—Adequate cooking of pork. Proper disposal of human waste.

Hymenolepis nana

H. nana infection is the most common tapeworm in the United States. Infection is usually asymptomatic. It is endemic in the southeastern states, mostly in children. It is called the dwarf tapeworm because of its small size. It is also different from other tapeworms because the eggs are directly infectious for humans without the need for an intermediate animal host. Diagnosis is made by finding eggs in feces. Treat with praziquantel. No specific means of prevention.

TREMATODES (CHAPTER 55)

Schistosoma (Schistosoma mansoni, Schistosoma japonicum, & Schistosoma haematobium)

Disease—Schistosomiasis.

Characteristics—Trematode (blood fluke). Adults exist as two sexes but are attached to each other. Eggs are distinguished by spines: Schistosoma mansoni has large lateral spine; Schistosoma japonicum has small lateral spine; Schistosoma haematobium has terminal spine. Life cycle: Humans are infected by cercariae penetrating skin. Cercariae form larvae that penetrate blood vessels and are carried to the liver, where they become adults. The adult flukes migrate retrograde in the portal vein to reach the mesenteric venules (S. mansoni and S. japonicum) or urinary bladder venules (S. haematobium). Eggs penetrate the gut or bladder wall, are excreted, and hatch in fresh water. The ciliated larvae (miracidia) penetrate snails and multiply through generations to produce many free-swimming cercariae.

Transmission and Epidemiology—Transmitted by penetration of skin by cercariae. Humans are definitive hosts; snails are intermediate hosts. Endemic in tropical areas: S. mansoni in Africa and Latin America, S. haematobium in Africa and Middle East, S. japonicum in Asia.

Pathogenesis—Eggs in tissue induce inflammation, granulomas, fibrosis, and obstruction, especially in liver and spleen. S. mansoni damages the colon (inferior mesenteric venules), S. japonicum damages the small intestine (superior mesenteric venules), and S. haematobium damages the bladder. Bladder damage predisposes to carcinoma.

Laboratory Diagnosis—Eggs visible in feces or urine. Eosinophilia occurs.

Treatment—Praziquantel.

Prevention—Proper disposal of human waste. Swimming in endemic areas should be avoided.

Clonorchis sinensis

Disease—Clonorchiasis.

Characteristics—Trematode (liver fluke). Life cycle: Humans ingest undercooked fish containing encysted larvae (metacercariae). In duodenum, immature flukes enter biliary duct, become adults, and release eggs that are passed in feces. Eggs are eaten by snails; the eggs hatch and form miracidia. These multiply through generations (rediae) and then produce many free-swimming cercariae, which encyst under scales of fish and are eaten by humans.

Transmission and Epidemiology—Transmitted by eating raw or undercooked freshwater fish. Humans are definitive hosts; snails and fish are first and second intermediate hosts, respectively. Endemic in Asia.

Pathogenesis—Inflammation of biliary tract.

Laboratory Diagnosis—Eggs visible in feces.

Treatment—Praziquantel.

Prevention—Adequate cooking of fish. Proper disposal of human waste.

Paragonimus westermani

Disease—Paragonimiasis.

Characteristics—Trematode (lung fluke). Life cycle: Humans ingest undercooked freshwater crab meat containing encysted larvae (metacercariae). In gut, immature flukes enter peritoneal cavity, burrow through diaphragm into lung parenchyma, and become adults. Eggs enter bronchioles and are coughed up or swallowed. In fresh water, eggs hatch, releasing miracidia that enter snails, multiply through generations (rediae), and then form many cercariae that infect and encyst in crabs.

Transmission and Epidemiology—Transmitted by eating raw or undercooked crab meat. Humans are definitive hosts; snails and crabs are first and second intermediate hosts, respectively. Endemic in Asia and India.

Pathogenesis—Inflammation and secondary bacterial infection of lung.

Laboratory Diagnosis—Eggs visible in sputum or feces.

Treatment—Praziquantel.

Prevention—Adequate cooking of crabs. Proper disposal of human waste.

NEMATODES (CHAPTER 56)

1. Intestinal Infection

Ancylostoma duodenale & Necator americanus

Disease—Hookworm.

Characteristics—Intestinal nematode. Life cycle: Filariform larvae penetrate skin, enter the blood, and migrate to the lungs. They enter alveoli, pass up the trachea, then are swallowed. They become adults in small intestine and attach to walls via teeth (Ancylostoma) or cutting plates (Necator). Eggs are passed in feces and form noninfectious rhabditiform larvae and then infectious filariform larvae in soil.

Transmission and Epidemiology—Filariform larvae in soil penetrate skin of feet. Humans are the only hosts. Endemic in the tropics.

Pathogenesis—Anemia due to blood loss from GI tract.

Laboratory Diagnosis—Eggs visible in feces. Eosinophilia occurs.

Treatment—Mebendazole or pyrantel pamoate.

Prevention—Use of footwear. Proper disposal of human waste.

Ascaris lumbricoides

Disease—Ascariasis.

Characteristics—Intestinal nematode. Life cycle: Humans ingest eggs, which form larvae in gut. Larvae migrate through the blood to the lungs, where they enter the alveoli, pass up the trachea, and are swallowed. In the gut, they become adults and lay eggs that are passed in the feces. They embryonate (i.e., become infective) in soil.

Transmission and Epidemiology—Transmitted by food contaminated with soil containing eggs. Humans are the only hosts. Endemic in the tropics.

Pathogenesis—Larvae in lung can cause pneumonia. Heavy worm burden can cause intestinal obstruction or malnutrition.

Laboratory Diagnosis—Eggs visible in feces. Eosinophilia occurs.

Treatment—Mebendazole or pyrantel pamoate.

Prevention—Proper disposal of human waste.

Enterobius vermicularis

Disease—Pinworm infection.

Characteristics—Intestinal nematode. Life cycle: Humans ingest eggs, which develop into adults in gut. At night, females migrate from the anus and lay many eggs on skin and in environment. Embryo within egg becomes an infective larva within 4 to 6 hours. Reinfection is common.

Transmission and Epidemiology—Transmitted by ingesting eggs. Humans are the only hosts. Occurs worldwide.

Pathogenesis—Worms and eggs cause perianal pruritus.

Laboratory Diagnosis—Eggs visible by “Scotch tape” technique. Adult worms found in diapers.

Treatment—Mebendazole or pyrantel pamoate.

Prevention—None.

Strongyloides stercoralis

Disease—Strongyloidiasis.

Characteristics—Intestinal nematode. Life cycle: Filariform larvae penetrate skin, enter the blood, and migrate to the lungs. They move into alveoli and up the trachea and are swallowed. They become adults and enter the mucosa, where females produce eggs that hatch in the colon into noninfectious, rhabditiform larvae that are usually passed in feces. Occasionally, rhabditiform larvae molt in the gut to form infectious, filariform larvae that can enter the blood and migrate to the lung (autoinfection). The noninfectious larvae passed in feces form infectious filariform larvae in the soil. These larvae can either penetrate the skin or form adults. Adult worms in soil can undergo several entire life cycles there. This free-living cycle can be interrupted when filariform larvae contact the skin.

Transmission and Epidemiology—Filariform larvae in soil penetrate skin. Endemic in the tropics.

Pathogenesis—Little effect in immunocompetent persons. In immunocompromised persons, massive superinfection can occur, accompanied by secondary bacterial infections.

Laboratory Diagnosis—Larvae visible in stool. Eosinophilia occurs.

Treatment—Ivermectin is the drug of choice. Thiabendazole is an alternative.

Prevention—Proper disposal of human waste.

Trichinella spiralis

Disease—Trichinosis.

Characteristics—Intestinal nematode that encysts in tissue. Life cycle: Humans ingest undercooked meat containing encysted larvae, which mature into adults in small intestine. Female worms release larvae that enter blood and migrate to skeletal muscle or brain, where they encyst.

Transmission and Epidemiology—Transmitted by ingestion of raw or undercooked meat, usually pork. Reservoir hosts are primarily pigs and rats. Humans are dead-end hosts. Occurs worldwide but endemic in Eastern Europe and west Africa.

Pathogenesis—Larvae encyst within striated muscle cells called “nurse cells,” causing inflammation of muscle.

Laboratory Diagnosis—Encysted larvae visible in muscle biopsy. Eosinophilia occurs. Serologic tests positive.

Treatment—Thiabendazole effective early against adult worms. For severe symptoms, steroids plus mebendazole can be tried.

Prevention—Adequate cooking of pork.

Trichuris trichiura

Disease—Whipworm infection.

Characteristics—Intestinal nematode. Life cycle: Humans ingest eggs, which develop into adults in gut. Eggs are passed in feces into soil, where they embryonate (i.e., become infectious).

Transmission and Epidemiology—Transmitted by food or water contaminated with soil containing eggs. Humans are the only hosts. Occurs worldwide, especially in the tropics.

Pathogenesis—Worm in gut usually causes little damage.

Laboratory Diagnosis—Eggs visible in feces.

Treatment—Mebendazole.

Prevention—Proper disposal of human waste.

2. Tissue Infection

Dracunculus medinensis

Disease—Dracunculiasis.

Characteristics—Tissue nematode. Life cycle: Humans ingest copepods containing infective larvae in drinking water. Larvae are released in gut, migrate to body cavity, mature, and mate. Fertilized female migrates to subcutaneous tissue and forms a papule, which ulcerates. Motile larvae are released into water, where they are eaten by copepods and form infective larvae.

Transmission and Epidemiology—Transmitted by copepods in drinking water. Humans are major definitive hosts. Many domestic animals are reservoir hosts. Endemic in tropical Africa, Middle East, and India.

Pathogenesis—Adult worms in skin cause inflammation and ulceration.

Laboratory Diagnosis—Not useful.

Treatment—Thiabendazole or metronidazole. Extraction of worm from skin ulcer.

Prevention—Purification of drinking water.

Loa loa

Disease—Loiasis.

Characteristics—Tissue nematode. Life cycle: Bite of deer fly (mango fly) deposits infective larvae, which crawl into the skin and develop into adults that migrate subcutaneously. Females produce microfilariae, which enter the blood. These are ingested by deer flies, in which the infective larvae are formed.

Transmission and Epidemiology—Transmitted by deer flies. Humans are the only definitive hosts. No animal reservoir. Endemic in central and west Africa.

Pathogenesis—Hypersensitivity to adult worms causes “swelling” in skin. Adult worm seen crawling across conjunctivas.

Laboratory Diagnosis—Microfilariae visible on blood smear.

Treatment—Diethylcarbamazine.

Prevention—Deer fly control.

Onchocerca volvulus

Disease—Onchocerciasis (river blindness).

Characteristics—Tissue nematodes. Life cycle: Bite of female blackfly deposits larvae in subcutaneous tissue, where they mature into adult worms within skin nodules. Females produce microfilariae, which migrate in interstitial fluids and are ingested by blackflies, in which the infective larvae are formed.

Transmission and Epidemiology—Transmitted by female blackflies. Humans are the only definitive hosts. No animal reservoir. Endemic along rivers of tropical Africa and Central America.

Pathogenesis—Microfilariae in eye ultimately can cause blindness (“river blindness”). Adult worms induce inflammatory nodules in skin. See scaly dermatitis called “lizard skin.” Also loss of subcutaneous tissue called “hanging groin.”

Laboratory Diagnosis—Microfilariae visible in skin biopsy, not in blood.

Treatment—Ivermectin affects microfilariae, not adult worms. Suramin for adult worms.

Prevention—Blackfly control and ivermectin.

Wuchereria bancrofti

Disease—Filariasis.

Characteristics—Tissue nematodes. Life cycle: Bite of female mosquito deposits infective larvae that penetrate bite wound, form adults, and produce microfilariae. These circulate in the blood, chiefly at night, and are ingested by mosquitoes, in which the infective larvae are formed.

Transmission and Epidemiology—Transmitted by female mosquitoes of several genera, especially Anopheles and Culex, depending on geography. Humans are the only definitive hosts. Endemic in many tropical areas.

Pathogenesis—Adult worms cause inflammation that blocks lymphatic vessels (elephantiasis). Chronic, repeated infection required for symptoms to occur.

Laboratory Diagnosis—Microfilariae visible on blood smear.

Treatment—Diethylcarbamazine affects microfilariae. No treatment for adult worms.

Prevention—Mosquito control.

3. Nematodes Whose Larvae Cause Disease

Toxocara canis

Disease—Visceral larva migrans.

Characteristics—Nematode larvae cause disease. Life cycle in humans: Toxocara eggs are passed in dog feces and ingested by humans. They hatch into larvae in small intestine; larvae enter the blood and migrate to organs, especially liver, brain, and eyes, where they are trapped and die.

Transmission and Epidemiology—Transmitted by ingestion of eggs in food or water contaminated with dog feces. Dogs are definitive hosts. Humans are dead-end hosts.

Pathogenesis—Granulomas form around dead larvae. Granulomas in the retina can cause blindness.

Laboratory Diagnosis—Larvae visible in tissue. Serologic tests useful.

Treatment—Albendazole or mebendazole.

Prevention—Dogs should be dewormed.

Ancylostoma caninum & Ancylostoma braziliense

The filariform larvae of A. caninum (dog hookworm) and A. braziliense (cat hookworm) cause cutaneous larva migrans. The larvae in the soil burrow through the skin, then migrate within the subcutaneous tissue, causing a pruritic rash called “creeping eruption.” These organisms cannot complete their life cycle in humans. The diagnosis is made clinically. Thiabendazole is effective.

Anisakis simplex

The larvae of A. simplex cause anisakiasis. They are ingested in raw seafood, such as sashimi and sushi, and migrate into the submucosa of the intestinal tract. Acute infection resembles appendicitis. Diagnosis is not dependent on the clinical laboratory. There is no effective drug therapy. Larvae can be removed when visualized during gastroscopy. Prevention consists of not eating raw fish.

SUMMARIES OF MEDICALLY IMPORTANT ECTOPARASITES

ECTOPARASITES THAT CAUSE HUMAN DISEASE (CHAPTER 69)

1. Lice

Pediculus humanus & Phthirus pubis

Disease—Pediculosis.

Characteristics—Lice are easily visible. P. humanus has an elongated body, whereas P. pubis has a short body resembling a crab. Nits are the eggs of the louse, often attached to the hair shaft or clothing.

Transmission—Hair and body lice are transmitted from human to human by contact, especially fomites such as hats and combs. Pubic lice are transmitted by sexual contact.

Pathogenesis—Itching is caused by a hypersensitivity response to saliva of the louse.

Laboratory Diagnosis—Not involved.

Treatment—Permethrin. Ivermectin is also effective. Nits are removed from hair with a comb.

Prevention—Personal items should be treated or discarded.

2. Flies

Dermatobia hominis

Disease—Myiasis.

Characteristics—Fly larvae (maggots) cause the disease, not the adult flies.

TransmissionDermatobia deposits its egg on a mosquito, and when the mosquito bites, the eggs are then deposited on the skin. The warmth of the skin causes the egg to hatch, and the larva enters the skin at the site of the mosquito bite.

Pathogenesis—Larva induces an inflammatory response.

Laboratory Diagnosis—Not involved.

Treatment—Surgical removal of larva.

Prevention—Limit exposure to flies and mosquitoes.

3. Mites

Sarcoptes scabiei

Disease—Scabies.

Characteristics—Round body with eight short legs. Too small to be seen with naked eye.

Transmission—Person-to-person contact or fomites such as clothing.

Pathogenesis—Itching is caused by a hypersensitivity response to feces of the mite.

Laboratory Diagnosis—Microscopic examination reveals mites and their feces.

Treatment—Permethrin.

Prevention—Treat contacts and discard fomites.

4. Ticks

Dermacentor Species

Disease—Tick paralysis.

Characteristics—Certain species of ticks produce a neurotoxin.

Transmission—Ticks reside in grassy areas and attach to human skin.

Pathogenesis—Female tick requires a blood meal and toxin enters in tick saliva at bite site. Neurotoxin blocks release of acetyl choline at neuromuscular junction. Similar action as botulinum toxin.

Laboratory Diagnosis—Not involved.

Treatment—Removal of tick results in prompt reversal of paralysis.

Prevention—Remove ticks; wear protective clothing.

5. Spiders

Latrodectus mactans (Black Widow Spider)

Disease—Spider bite.

Characteristics—Black widow spiders have an orange-red hourglass on their ventral surface.

Pathogenesis—Neurotoxin causes pain in extremities and abdomen. Numbness, fever, and vomiting also occur.

Laboratory Diagnosis—Not involved.

Treatment—Antivenom should be given in severe cases.

Loxosceles reclusa (Brown Recluse Spider)

Disease—Spider bite.

Characteristics—Brown recluse spiders have a violin-shaped pattern on their dorsal surface.

Pathogenesis—Dermotoxin is a protease that causes painful necrotic lesions.

Laboratory Diagnosis—Not involved.

Treatment—Antivenom is not available in the United States.