Pediatric Residency Training Program


Infectious Diseases

Deborah Lehman M.D.

Srinath Sanda M.D.

Nirali P. Singh M.D.

  1. General Approach to the Child with Possible Infection
  2. Detailed history and physical examination is essential
  3. Historyshould include details about the present illness, significant past medical history, travel and animal contact, medications, unusual food ingestions (including raw meat and unpasteurized dairy products), and risk of infection with human immunodeficiency virus (HIV; e.g., intravenous drug use, remote history of blood transfusion, unprotected intercourse).
  4. Physical examinationshould be comprehensive with special attention to general appearance, rashes, skin manifestations of endocarditis (see Chapter 8, section V.C), hepatosplenomegaly, evidence of joint effusion, and lymph node enlargement.
  5. Use of the laboratory

Pathogens may be identified by direct or indirect laboratory methods.

  1. Direct methods
  2. Culturesfor bacteria and viruses
  3. Microbiologic stains, including Gram stainZiehl-Neelsen stain(acid-fast bacilli), silver stain (fungal elements), and Wright stain (stool white blood cells [WBCs])
  4. Fluorescent antibody-antigen stainingfor herpes simplex virus (HSV) 1 and 2, varicella-zoster virus (VZV), and respiratory viruses, such as respiratory syncytial virus (RSV), adenovirus, influenza A and B, and parainfluenza
  5. Direct observation, including wet mountfor fungal elements and Trichomonas vaginalis and dark-field microscopy for Treponema pallidum
  6. Polymerase chain reaction (PCR)is now available for identification and quantification of many pathogens.


  1. Indirect methods
  2. Intradermal skin testingfor Mycobacterium tuberculosis (TB) and Coccidioides immitis
  3. Antibody testingfor viruses (Epstein-Barr virus, cytomegalovirus [CMV], VZV, and HIV), Toxoplasma gondiiBartonella henselae, and Mycoplasma pneumoniae.
  4. Nonspecificlaboratory indications of infection typically include elevation of acute-phase reactants, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).
  5. Evaluation of the Child with Fever
  6. Fever

in children is defined as a rectal temperature of 38°C (100.4°F) or higher. Temperatures taken by axillary, oral, or tympanic methods may be less accurate.


Evaluation for serious bacterial infection (e.g., meningitis, pneumonia, sepsis, bone and joint infections, urinary tract infection, and enteritis) should occur in the following high-risk groups:

  1. Young infants, especially those younger than 28 days, because of immaturity of their immune system
  2. Older infantswith high fevers(temperature > 39°C [102.2°F]) who appear ill
  3. Infants and children who are immunodeficient, have sickle cell disease, or have underlying chronic liver, renal, pulmonary, or cardiac disease
  4. Evaluation of fever in infants < 3 months
  5. Epidemiology. 3 to 10% of well-appearing, and 17% of “toxic”-appearing, febrile infants have serious bacterial infections. (Toxic appearance refers to a child appearing extremely ill with diminished interactivity or poor peripheral perfusion.)
  6. Etiology
  7. Infectionsmay be acquired in several ways. Infections may be transplacental, acquired during passage through the birth canal, or transmitted postnatally in the nursery or at home.
  8. Viruses are the most common organisms causing infection.
  9. Common bacterial organismscausing infection in this age group are summarized in Table 7-1.
  10. Clinical featuresof infection in young infants are often nonspecific and include fever, diminished appetite, irritability, cough, rhinorrhea, vomiting, diarrhea, and apnea.
  11. Diagnosis. Clinical and laboratory features may be used to identify infants at low risk for serious bacterial infection.
  12. Infants who are well-appearing and previously healthy, who have had no recent antibiotic therapy, and who have no site of focal infection on examination are at low risk for serious bacterial infection. Infants who are ill-appearing or toxic and who have evidence of a focal infection on examination are at higher risk for serious bacterial infection.



Table 7-1. Typical Bacterial Pathogens and Empiric Antibiotics for Infants and Children with Suspected Sepsis or Meningitis


Bacterial Pathogens

Empiric Intravenous Antibiotics

0–1 month

Group B streptococcus
Escherichia coli
Listeria monocytogenes

Ampicillin + gentamicin or cefotaxime

1–3 months

Group B streptococcus
Streptococcus pneumoniae
Listeria monocytogenes

Ampicillin + cefotaxime (+ vancomycin if bacterial meningitis suspected)

3 months–3 years

Streptococcus pneumoniae
Haemophilus influenzae type b
Neisseria meningitidis

Cefotaxime (+ vancomycin if bacterial meningitis suspected)

3 years–adult

Streptococcus pneumoniae
Neisseria meningitidis

Cefotaxime (+ vancomycin if bacterial meningitis suspected)

  1. Laboratory evaluationshould include complete blood count (CBC), blood cultures, urinalysis, urine culture, chest radiograph if tachypnea or respiratory distress is present, and analysis of cerebrospinal fluid. Criteria that indicate an infant is at low risk for serious bacterial infection include:
  2. WBC > 5, 000 and < 15, 000 cells/mm3
  3. Absolute band count < 1, 500 cells/mm3
  4. Normal urinalysis (< 10 WBCs per high-power field)
  5. If diarrhea is present, < 5 WBCs per high-power field on stool Wright stain
  6. Normal cerebrospinal fluid (CSF)
  7. Management
  8. Hospitalizationis required for:
  9. All infants ≤ 28 days of age
  10. Infants between 29 days and 3 months with any of the following:
  11. Toxic appearance on examination
  12. Suspected meningitis
  13. Pneumonia, pyelonephritis, or bone and soft tissue infectionsunresponsive to oral antibiotics
  14. Patients in social circumstances in which there is uncertain outpatient care and follow-up
  15. Antibiotic managementis based on age, risk factors for infection, and etiology.
  16. Infants ≤ 28 days of age require intravenous antibiotics in the hospital until cultures of blood, urine, CSF, and stool, if diarrhea is present, are negative.
  17. Infants 29 days–3 months who satisfy low-risk clinical and laboratory criteria (see section II.C.4) and who have transportation and good outpatient follow-up may be managed safely with empiric outpatient parenteral antibiotic therapy on a daily basis (i.e., intramuscular Ceftriaxone) while cultures are pending.



  1. Infants 29 days–3 months who do not meet low-risk clinical and laboratory criteria should be hospitalized for parenteral therapy while cultures are pending.
  2. Recommended parenteral antibiotic therapy for hospitalized infants is presented in Table 7-1.
  3. Evaluation of fever in children 3–36 months
  4. Epidemiology.Risk of serious bacterial infection is 3–10%, and the likelihood of bacteremia increases with increasing fever and peripheral WBC.
  5. Etiology(see Table 7-1). Streptococcus pneumoniae is the most common organism. Haemophilus influenzae type b (HIB) is less common as a result of the introduction of HIB vaccine.
  6. Diagnostic evaluationand management are based on the degree of the fever and whether the child appears toxic.
  7. If the child is toxic-appearing, a complete evaluation for sepsis, intravenous antibiotics, and hospitalization are required.
  8. If the child is nontoxic-appearing and the temperature is < 39°C (< 102.2°F), no laboratory tests are required and the child may be observed closely at home.
  9. If the child is nontoxic-appearing and has a temperature > 39°C (> 102.2°F), the following studies are suggested:
  10. Urine culture for males < 6 months of age and females < 2 years of age
  11. Blood culture for all children or only for those whose WBC > 15, 000 cells/mm3
  12. Chest radiograph if respiratory distress, rales, or tachypneais present
  13. Stool culture if there is blood and mucus in the stool or if there are ≥ 5 WBCs per high-power field on Wright stain
  14. Empiric antibiotics for all children or only for those whose WBC > 15, 000 cells/mm3. Reevaluation in 24–48 hours.
  15. Recommended parenteral antibiotic therapy for hospitalized infants and children is presented in Table 7-1.

III. Fever of Unknown Origin (FUO)

  1. Definition

Fever of unknown origin is a term used to describe a fever lasting longer than 8 days to 3 weeks (experts disagree about the length of time of fever necessary to diagnose fever as FUO) when prior history, physical examination, and preliminary laboratory evaluation have all failed to lead to a diagnosis.

  1. Etiology
  2. Most children with FUO do not have a rare illnessbut rather a common infection with an unusual presentation.



  1. The differential diagnosisis extensive (Table 7-2).
  2. One fourth of cases of FUO resolve spontaneouslywithout a diagnosis having been made.
  3. Evaluation

should include the following:

  1. Comprehensive history, focusing on a thorough review of systems(especially weight loss, rashes, fever, and stool patterns), past medical and surgical history (including prior blood transfusions), travel history, animal exposure, and family and social history.
  2. Detailed physical examination, focusing on general appearance and growth curves, skin and mucous membrane findings, presence of lymphadenopathy and hepatosplenomegaly, and evaluation of joints and bones.
  3. Laboratory studiesare based on the history and physical examination and often include:
  4. CBC with differentialto evaluate for infection or leukemia
  5. ESR or CRP, which are nonspecific indicators of tissue inflammation
  6. Serum transaminasesto evaluate for hepatitis
  7. Urinalysis and urine cultureto evaluate for infection

Table 7-2. Differential Diagnosis of Fever of Unknown Origin

Infectious disorders (most common cause of FUO)
   Occult infection (e.g., pyelonephritis, sinusitis, mastoiditis, otitis media)
   Viral syndromes (e.g., Epstein-Barr, cytomegalovirus, enterovirus, hepatitis B, HIV, parvovirus B19)
   Occult bacteremia (e.g., salmonellosis, tularemia, brucellosis, gonococcemia)
   Bacterial endocarditis
   Occult abscess (e.g., liver, intra-abdominal, or perinephric)
   Musculoskeletal infections (e.g., diskitis, osteomyelitis, septic arthritis)
   Spirochete infections (e.g., Lyme disease, leptospirosis)
   Parasitic infections (e.g., malaria, toxoplasmosis)
   Cat scratch disease (Bartonella henselae)
Rheumatologic disorders (second most common cause of FUO)
   Systemic-onset juvenile rheumatoid arthritis (Still's disease)
   Kawasaki disease
   Systemic lupus erythematosus
   Acute rheumatic fever
   Polyarteritis nodosum
Malignancy (third most common cause of FUO)
Periodic disorders characterized by spiking fevers at regular monthly intervals
   Familial Mediterranean fever: fever, peritonitis, pleuritis, and monoarthritis
   Periodic fever syndrome or periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome (PFAPA)
   Cyclic neutropenia: neutropenia at time of fever occurring at regular 21-day intervals
Miscellaneous causes
   Inflammatory bowel disease
   Drug fever
   Factitious disorder

FUO = fever of unknown origin; HIV = human immunodeficiency virus.

  1. P.186
  2. Blood culturesto evaluate for bacteremia, including endocarditis
  3. Anti-streptolysin O titerto evaluate for prior streptococcal infection, as seen in rheumatic fever
  4. Antinuclear antibody (ANA) and rheumatoid factor (RF)to screen for rheumatic diseases
  5. Stoolfor culture, ova and parasites, and Clostridium difficile toxin if diarrhea is present
  6. Tuberculosis skin test
  7. HIV testing
  8. Imaging optionsmay include chest radiography, echocardiography to evaluate for bacterial endocarditis, bone scanning to evaluate for osteomyelitis, gallium scanning to assess for sites of inflammation, and computed tomography (CT) and magnetic resonance imaging (MRI).
  9. Management.Hospitalization is generally recommended for children with fever for greater than 2 weeks to facilitate evaluation and to document fever and coexisting symptoms. Specific management is based on the identified cause of the FUO.
  10. Meningitis
  11. Definition

Meningitis is inflammation of the meninges and is classified as bacterial or aseptic.

  1. Bacterial Meningitis
  2. Epidemiology
  3. Highest incidence of bacterial meningitis is during the first month of life.
  4. Overall incidence during childhood has declined because of the introduction of the conjugate vaccine for HIB.
  5. Risk factorsfor bacterial meningitis:
  6. Young age
  7. Immunodeficiency(e.g., asplenia, humoral-mediated immunodeficiency, and terminal complement deficiency)
  8. Anatomic defects(e.g., basilar skull fracture, ventriculoperitoneal shunt)
  9. Etiology.Causes of infection are based on the age of the child (see Table 7-1).
  10. Clinical features
  11. Infants and young children often have minimal and nonspecific signs and symptoms(e.g., poor feeding, irritability, lethargy, respiratory distress). Fever may be absent or minimal. A bulging fontanelle may be present on physical examination.
  12. Older children often present with feverand signs suggestive of meningeal irritation.
  13. Alteration in level of consciousness, with irritability, somnolence, or obtundation



  1. Nuchal rigidityand positive Kernig's and Brudzinski's signs (these signs are less reliably present in infants and young children)
  2. Seizures
  3. Photophobia
  4. Emesis
  5. Headache
  6. Diagnosis. Index of suspicion for bacterial meningitis should be especially high in febrile, irritable infants.Evaluation of all children with suspected bacterial meningitis should include:
  7. Lumbar puncture, which may demonstrate:
  8. Pleocytosiswith a predominance of neutrophils. The CSF WBC often exceeds 5, 000 cells/mm3.
  9. Hypoglycorrhachia(low CSF glucose)—ratio of CSF to serum glucose < 0.40.
  10. Increased protein
  11. Positive Gram stain and culture
  12. Bacterial antigens may be tested but have a low sensitivity and are not recommended on a routine basis.
  13. Pretreatment with antibiotics may sterilize the CSF culture but should not alter the CSF cellular and biochemical profile above.
  14. See Table 7-3for a comparison of the CSF profile in bacterial, viral, tuberculous, and fungal meningitis.
  15. Blood cultureis positive in the majority of cases of bacterial meningitis.
  16. CT scan with contrastto evaluate for brain abscess is often recommended, especially for patients with focal neurologic findings.
  17. Management. Early, empiric treatment of bacterial meningitis is critical.
  18. Antibiotic therapyvaries based on age of child and the most likely pathogens:
  19. Newborns(0–28 days): ampicillin plus aminoglycoside or third-generation cephalosporin. (Intravenous acyclovir for possible HSV infection should also be considered for ill neonates, especially those presenting with apnea, seizures, or cutaneous vesicles.)
  20. Young infants(1–3 months): ampicillin plus third-generation cephalosporin. (Add vancomycin if bacterial meningitis is highly suspected, given the potential resistance pattern of pneumococcus.)
  21. Older infants and children(> 3 months): third-generation cephalosporin. (Add vancomycin if bacterial meningitis is highly suspected, given the potential resistance pattern of pneumococcus.)
  22. Corticosteroidsgiven before or with the first dose of antibiotics have been shown to be effective at reducing the incidence of hearing loss in HIB meningitis. Efficacy in other causes of bacterial meningitis has not been demonstrated.
  23. Supportive careincludes attention to fluids with rehydration to normovolemic status, followed by administration of maintenance fluids with close attention to urine output, specific gravity, and serum sodium to monitor for the development of the syndrome of inappropriate release of antidiuretic hormone (SIADH).



Table 7-3. Cerebrospinal Fluid Profiles in Meningitis


WBC Differential (cells/mm3)



Gram Stain, Culture, and Other Definitive Tests

Acute bacterial

PMNs predominate



Positive culture and Gram stain

Partially treated bacterial

Monos predominate

Normal to high

Low normal

Negative culture and usually negative Gram stain
(+) CSF bacterial antigens


PMNs early, then monos + lymphs
HSV encephalitis may show RBCs

Normal to high


Enterovirus may be recovered by culture
Enterovirus and HSV may be identified by PCR


Lymphs predominate

Very high

Low to very low

AFB smear and culture rarely positive
PCR may be positive


Lymphs predominate

Normal to high


Culture may be positive
India ink (+) with Cryptococcus

Parameningeal focus (brain abscess)

Polys or monos predominate



Negative culture

AFB = acid-fast bacteria; PMNs = polymorphonuclear cells; monos = mononuclear cells; lymphs = lymphocytes; CSF = cerebrospinal fluid; PCR = polymerase chain reaction; RBCs = red blood cells; HSV = herpes simplex virus; WBC = white blood cell.

  1. Complications.Complication rates are highest with meningitis caused by Gram-negative organisms, followed by S. pneumoniae, HIB, and, finally, Neisseria meningitidis. Mortality rates range from 5 to 50% depending on the infecting bacteria.
  2. Hearing lossis the most common complication occurring in up to 25% of patients.
  3. Global brain injuryoccurs in 5–10% of patients.
  4. Other complications include SIADHseizures, hydrocephalus, brain abscess, cranial nerve palsy, learning disability, and focal neurologic deficits.
  5. Aseptic Meningitis
  6. Definition.Aseptic meningitis is inflammation of the meninges with a CSF lymphocytic pleocytosis and, if caused by a virus, normal CSF glucose and normal to minimally elevated CSF protein.



  1. Etiology (Table 7-4).Most causes of aseptic meningitis are viral.
  2. Clinical featuresmay be similar to those found in bacterial meningitis.
  3. Symptoms of viral meningitis may be mild with fever, headache, and emesis, or severe with altered level of consciousness and seizures.
  4. Symptoms in aseptic meningitis caused by M. tuberculosis(TB) may be nonspecific initially with lethargy or irritability, but during the second week of illness, symptoms progress rapidly with findings that include cranial nerve deficits, altered level of consciousness, coma, paraplegia, and eventual death if untreated.
  5. Diagnosis(see Table 7-3 for the CSF variables commonly seen in viral, fungal, tuberculous, and bacterial meningitis)
  6. Viral meningitis
  7. Viral culture of CSF may be performed; however, the virus may not grow for 10–14 days.
  8. PCR technology is available for the detection of Epstein-Barr virus (EBV), CMV, HSV, and enteroviruses.
  9. Positive surface cultures for enterovirus from throat and rectum may be suggestive in cases of enteroviral meningitis.
  10. TB meningitis.CSF findings include lymphocytic pleocytosis, hypoglycorrhachia, and dramatically elevated protein. Brain imaging shows a characteristic basilar enhancement.Positive CSF acid-fast bacterial (AFB) stains (although rarely positive in TB meningitis), positive culture (may take as long as 6 weeks for growth), or positive PCR findings are diagnostic. Fifty percent of patients have a negative chest radiograph and tuberculin skin test at presentation.

Table 7-4. Causes of Aseptic Meningitis

Viral meningitis (most common cause of aseptic meningitis). If infection also involves the brain, it is termed a meningoencephalitis.
   Enteroviruses (most common cause of viral meningitis in the U.S.; most common in the summer and fall)
   Lymphocytic choriomeningitis
   Herpes viruses (herpes simplex virus, Epstein-Barr virus, cytomegalovirus, varicella zoster virus)
   Viruses that commonly cause encephalitis include arboviruses (St. Louis, Western equine, Eastern equine, West Nile virus),influenza, and the herpes viruses
Bacterial causes (some bacteria may cause an aseptic picture)
   Mycobacterium tuberculosis (most commonly seen in children younger than 5 years of age)
   Borrelia burgdorferi (Lyme disease)
   Treponema pallidum (syphilis)
Fungal causes
   Coccidioides immitis
   Cryptococcus neoformans
   Histoplasmosis capsulatum
Parasitic causes
   Taenia solium (etiologic agent of cysticercosis)
   Toxoplasma gondii (in immunocompromised patients)

  1. P.190
  2. Diagnostic studies that may identify other causes of aseptic meningitisinclude CSF rapid plasma reagent (RPR) for syphilis, India ink for fungus (cryptococcus), cryptococcal antigen tests, and CSF and serum antibody testing for coccidioidomycosis, Lyme disease, and cysticercosis.
  3. Management
  4. Most causes of viral meningitis are self-limited.
  5. TB meningitis is treated with four medications, including isoniazid, rifampin, pyrazinamide, and streptomycin. Corticosteroids are also commonly used.
  6. Prognosisof aseptic meningitis is dependent on the causative agent and ranges from excellent in enteroviral meningitis to poor in TB meningitis (20% mortality in young children).
  7. Upper Respiratory Infections
  8. General Concepts

Upper respiratory infections (URIs) account for the majority of pediatric acute illness visits. Although generally benign illnesses, they may cause significant morbidity and parental anxiety.

  1. Simple Upper Respiratory Infection (common cold)
  2. Etiology.More than 100 viruses have been implicated and include rhinovirus, parainfluenza virus, coronavirus, and respiratory syncytial virus.
  3. Clinical features
  4. Presenting symptoms include low-grade fever, rhinorrhea, cough, and sore throat. Symptoms resolve within 7–10 days.
  5. Color of nasal discharge alone does not predict the presence of concurrent sinusitisbecause purulent nasal discharge may occur early in the course of a URI.
  6. Persistent symptoms(> 10 days) or fever should prompt the clinician to evaluate for bacterial superinfection (e.g., sinusitis, acute otitis media).
  7. Diagnosisis based on clinical features. The viral agent is rarely identified.
  8. Management.The most important step is to ensure adequate hydration, particularly in young children, and to exclude more serious disorders such as sinusitis and acute otitis media. Over-the-counter medications (e.g., antihistamines, mucolytics, cough suppressant, decongestants) have minimal effectiveness and may cause side effects. Antibiotics have no role in management.
  9. Sinusitis
  10. Development of the sinuses.Ethmoid and maxillary sinuses form in the third to fourth month of gestation and are present at birth. The sphenoid sinuses develop between 3 and 5 years of age and frontal sinuses between 7 and 10 years of age.
  11. Categories of sinusitis.Sinusitis is divided into acute, subacute, and chronic forms on the basis of duration of symptoms. Clinical features, causes, and management of sinusitis are presented in Figure 7-1.



  1. Diagnosisis based on clinical features. Note that physical examination (particularly sinus transillumination) is unreliable for diagnosis and that imaging is not useful for the initial diagnosis or management of uncomplicated sinusitis.
  2. Pharyngitis
  3. Etiology
  4. Viral causesinclude those viruses associated with simple URIs, as well as coxsackievirus, EBV, and CMV.
  5. Bacterial causesinclude Streptococcus pyogenes (group A β-hemolytic streptococcus [GABHS] or “strep throat”), Arcanobacterium hemolyticum, and Corynebacterium diphtheriae (diphtheria).
  6. Clinical features.The clinical features of viral pharyngitis and GABHS pharyngitis overlap, resulting in difficulty differentiating between the two conditions solely on the basis of history and physical examination.

Figure 7-1. Diagnosis of sinusitis and clinical features, etiology, and management. CT = computed tomography; IV = intravenous.

  1. P.192
  2. Viral pharyngitismay present with simple URI symptoms. Tonsillar exudates may also be present. Certain viral infections may have the following specific findings:
  3. Children with EBV pharyngitismay present with enlarged posterior cervical lymph nodes, malaise, and hepatosplenomegaly.
  4. Children with coxsackievirus pharyngitismay present with painful vesicles or ulcers on the posterior pharynx and soft palate (herpangina). Blisters may also be present on the palms and soles (hand-foot-mouth disease).
  5. Bacterial pharyngitis
  6. GABHS pharyngitis(strep throat) is usually seen in school-age children (5–15 years of age) and in the winter and spring. Although it is difficult to distinguish GABHS pharyngitis from viral pharyngitis on the basis of signs and symptoms, GABHS infection has the following characteristics:
  7. Lack of other URI symptoms(e.g., rhinorrhea, cough)
  8. Exudates on the tonsils, petechiae on the soft palate, strawberry tongue, and enlarged tender anterior cervical lymph nodes
  9. Fever
  10. Scarlatiniform rashin some patients (see section IX.A.5)
  11. Complications of GABHS infection are described in section IX.A.5.g.
  12. Diphtheriais extremely rare in developed nations because of universal vaccination. Patients present with low-grade fever and a gray, adherent tonsillar membrane. Toxin-mediated cardiac and neurologic complications may also develop.
  13. Diagnosis
  14. Patients with suspected GABHS pharyngitis should undergo culture (gold standard) or antigen testing (“rapid strep test”) to confirm GABHS pharyngitis and to avoid overuse of antibiotics.
  15. Because 5% of the population carries GABHS in the pharynx (GABHS carriers), culture or rapid antigen testing should be limited to symptomatic patients who lack concomitant viral symptoms.
  16. Management
  17. Management of viral pharyngitis is supportive and includes analgesics and maintenance of adequate hydration.
  18. Management of GABHS pharyngitis includes oral penicillin VK, a single dose of intramuscular benzathine penicillin, and for penicillin-allergic patients, oral erythromycin or macrolides.
  19. Management of severe EBV pharyngitis may sometimes include corticosteroids.
  20. Diphtheria is treated with oral erythromycin or parenteral penicillin, and a specific antitoxin that is available from the U.S. Centers for Disease Control and Prevention. Respiratory isolation is very important to prevent spread of infection.



  1. Acute Otitis Media
  2. Definitions
  3. Acute otitis media (AOM)is defined as an acute infection of the middle ear space.
  4. Otitis media with effusion (OME)is defined as fluid within the middle ear space without symptoms of infection.
  5. Etiology.Bacterial pathogens include S. pneumoniaenon-typeable H. influenzae, and Moraxella catarrhalis. Viruses causing simple URIs also commonly cause AOM.
  6. Clinical features of AOM
  7. AOM usually develops during or after a simple URI.
  8. Symptoms may include fever, ear pain, and decreased hearing.Symptoms are less reliably present in young children.
  9. If the tympanic membrane perforates, patients may report pus or fluid draining from the ear.
  10. Diagnosis
  11. Proper diagnosis of AOM depends on the identification of fluid within the middle ear space in the presence of symptoms of infection.
  12. Pneumatic otoscopyto identify abnormal movement of the tympanic membrane, and therefore fluid within the middle ear, is an essential component of the physical examination and is the most reliable method of detecting middle ear fluid.
  13. Erythema and loss of tympanic membrane landmarks are unreliable methods of identifying fluid within the middle ear space.
  14. Although not routine, identification of the bacterial etiology may be made by tympanocentesis.
  15. A perforated tympanic membrane with purulent discharge within the external auditory canal is also consistent with the diagnosis of AOM.
  16. Management
  17. Antibiotics are often prescribed for AOM; however, their use is controversial, especially in older children, because a majority of cases of AOM resolve spontaneously without complications.
  18. Initial antibiotic therapy, if used, is usually amoxicillin.If the patient attends a day care facility or has received antibiotics within the previous 1–2 months, then the likelihood of infection with penicillin-resistant S. pneumoniae increases. Initial therapy may then include high-dose amoxicillin, amoxicillin-clavulanic acid, or a cephalosporin. Macrolides may be used in penicillin-allergic patients.
  19. Antibiotics are not indicated for OME.
  20. Otitis Externa
  21. Definition.Otitis externa (OE) is defined as an infection of the external auditory canal (EAC).
  22. Pathogenesis.Factors that interfere with the EAC protective mechanisms (e.g., cerumen removal, trauma, maceration of skin from swimming, or excessive moisture or humidity) predispose to OE.



  1. Etiology.Pathogens are most commonly Pseudomonas aeruginosaStaphylococcus aureus, or Candida albicans. OE can also develop in a patient with a perforated tympanic membrane secondary to AOM.
  2. Clinical features.Pain, itching, and drainage from the ear are usually present. Systemic symptoms are usually absent. A history consistent with AOM is helpful in determining whether there has been a tympanic membrane perforation.
  3. Diagnosis.Findings on physical examination are the basis of diagnosis. Erythema and edema of the EAC may be present, sometimes with purulent or whitish material within the canal. There may also be tenderness on palpation or movement of the tragus. Visualization of the tympanic membrane is important to exclude perforation. In refractory cases, cultures of infected material may identify the etiologic agent.
  4. Management
  5. The key to successful management is to restore the EAC to its natural acidic environment.
  6. For mild cases of OE (minimal pain and discharge), acetic acid solution may be sufficient to relieve the discomfort and to restore the natural environment of the EAC.
  7. For more severe cases, topical antibiotics (sometimes combined with a topical corticosteroid) are prescribed.
  8. Perforated AOM complicated by OE is treated with both oral and topical antibiotics.
  9. Middle and Lower Respiratory Infections

including pneumonia, bronchiolitis, epiglottitis, croup, and bacterial tracheitis, are described in Chapter 9, section III.

VII. Cervical Lymphadenitis

  1. Definition

Cervical lymphadenitis is defined as an enlarged, inflamed, tender lymph node or nodes in the cervical area.

  1. Etiology and Differential Diagnosis
  2. Localized bacterial infection
  3. S. aureusis the most common bacterial agent.
  4. S. pyogenesis also common.
  5. Mycobacterial infections, including M. tuberculosisand atypical mycobacterium (Mycobacterium avium complex)
  6. B. henselae, which causes cat scratch disease (see section XVII.B)
  7. Reactive lymphadenitisoccurs in response to infections in the pharynx, teeth, and soft tissues of the head and neck.
  8. Viral infections, such as EBV, CMV, and HIV, can also cause reactive lymphadenitis in the cervical area.



  1. Kawasaki diseasemay present with unilateral cervical lymphadenitis. (An enlarged cervical lymph node is one of the diagnostic criteria of Kawasaki disease.)
  2. T. gondiiinfection may cause a mononucleosis-like illness with cervical lymphadenopathy.
  3. Structural lesions in the neck(e.g., branchial cleft cyst, cystic hygroma) can become secondarily infected and may present similarly to cervical lymphadenitis.
  4. Clinical Features
  5. The infected node is mobile, tender, warm, and enlarged, and the overlying skin is erythematous. Fluctuance may be present.
  6. Nodes may be single, or multiple nodes may be clumped together in a mass.
  7. Systemic symptoms (e.g., fever) may be present.
  8. Diagnosis

is based on clinical features.

  1. Tests, such as placement of a tuberculin skin test, a CBC with differential, and antibody titers for B. henselaeand T. gondii, may be indicated for infected nodes unresponsive to therapy.
  2. Antibody titersfor EBV, CMV, and HIV serology may be indicated if lymphadenopathy is diffuse and persistent.
  3. Imaging studiesmay help define the anatomy of the cervical area and identify areas of suppuration or abscess that require surgical drainage. Imaging is essential if there is concern about airway compromise resulting from a deep infection.
  4. Management

includes empiric antibiotics directed toward the most common organisms (S. aureus and S. pyogenes). Initial treatment may include a first-generation cephalosporin or an anti-staphylococcal penicillin for 7–10 days. Intravenous antibiotics are indicated for the toxic-appearing child with adenitis or for the child who remains symptomatic despite appropriate oral therapy.

VIII. Parotitis

  1. Definition

Parotitis is defined as inflammation of the parotid salivary glands.

  1. Etiology
  2. Mumps and other viruses(e.g., CMV, EBV, HIV, influenza) usually cause bilateral involvement of the parotid gland. Before universal vaccination, mumps was the most common cause of parotitis.
  3. Bacterial parotitis (acute suppurative parotitis) is caused by S. aureusS. pyogenes, and M. tuberculosisand usually results in unilateral parotid involvement. Bacterial parotitis is uncommon during childhood, although children with decreased salivary flow or stone formation are at increased risk.
  4. Clinical features

include swelling centered above the angle of the jaw and fever. Physical examination of the oropharynx may reveal pus that can be expressed from Stensen's duct.



  1. Diagnosis

is based on clinical features and may be confirmed by CT scan.

  1. Culture of the drainage from Stensen's duct may reveal the microbiologic cause of bacterial parotitis.
  2. Viral parotitis may be diagnosed by viral serology. Mumps virus may also be detected in the urine.
  3. Management
  4. Viral parotitis is treated with supportive care and analgesics.
  5. Acute suppurative parotitis is treated with antibiotics directed against S. aureusand S. pyogenes. Rarely, surgical excision and drainage are required.
  6. Complications
  7. Mumps may also result in meningoencephalitis, orchitis and epididymitis, and pancreatitis.
  8. Acute suppurative parotitis may result in formation of an abscess and osteomyelitis of the jaw.
  9. Skin and Soft Tissue Infections
  10. Bacterial Infections
  11. Impetigo
  12. Definition.Impetigo is a superficial skin infection involving the upper dermis.
  13. Etiology.S. aureus is the most common agent, but GABHS (or S. pyogenes) may also cause infection.
  14. Clinical features. Honey-colored crustedor bullous lesions are present, commonly on the face, especially around the nares. Fever is generally absent. Infection is easily transmitted.
  15. Diagnosis.Visual inspection is the basis of diagnosis. Cultures are not required.
  16. Management.Treatment may include topical mupirocin or oral antibiotics, such as dicloxacillin, cephalexin, or clindamycin.
  17. Complications.Bacteremia, post-streptococcal glomerulonephritis (treatment of impetigo does not prevent this complication), and staphylococcal scalded skin syndrome (SSSS) are possible complications.
  18. Erysipelas
  19. Definition.Erysipelas is a skin infection that involves the dermal lymphatics.
  20. Etiologyis usually GABHS.
  21. Clinical featuresinclude tender, erythematous skin with a distinct border. The face and scalp are common locations.
  22. Diagnosisis by visual inspection.
  23. Managementincludes systemic therapy with antibiotics targeted against GABHS.



  1. Complicationsinclude bacteremia, post-streptococcal glomerulonephritis, and necrotizing fasciitis.
  2. Cellulitis
  3. Definition.Cellulitis is a skin infection that occurs within the dermis.
  4. Etiology.Causes include GABHS and S. aureus. Infection is usually caused by a break in the skin barrier allowing bacteria to gain entry beyond the protective layer of the epidermis.
  5. Clinical features.Cellulitis is characterized by erythema, warmth, and tenderness. The infected skin border is indistinct.
  6. Diagnosisis by visual inspection. Blood cultures are seldom positive. In more aggressive forms of cellulitis, biopsy and culture of the leading edge of infection may be useful to identify the pathogenic organism.
  7. Managementincludes oral or intravenous antibiotics directed against the typical causative agents, including first-generation cephalosporins or anti-staphylococcal penicillins.
  8. Important variants of cellulitis
  9. Buccal cellulitisis a now uncommon form of cellulitis that occurs as a unilateral bluish discoloration on the cheek of a young unimmunized child. Patients are often febrile and may appear toxic. The causative agent is HIB, and blood cultures are often positive. Management includes intravenous antibiotics directed against H. influenzae, usually a second- or third-generation cephalosporin (e.g., cefuroxime or cefotaxime). Patients with buccal cellulitis caused by HIB have a high rate of concomitant bacteremia and meningitis; a lumbar puncture should be performed.
  10. Perianal cellulitisoccurs as well-demarcated erythema involving the skin around the anus. Children may also present with constipation. The cause is usually GABHS. Diagnosis is by visual inspection or a positive rectal swab culture for GABHS. Management includes oral antibiotics (e.g., cephalexin, dicloxacillin).
  11. Necrotizing fasciitisis a potentially fatal form of deep cellulitis. Patients present with pain and systemic symptoms out of proportion to physical findings. Infection extends beyond the underlying fascia into the muscle. Examination may reveal crepitus and hemorrhagic bullae. The cause is polymicrobial and may involve GABHS and anaerobic bacteria. Intravenous antibiotics and surgical debridement are essential components of therapy.
  12. Staphylococcal scalded skin syndrome (SSSS)is caused by an S. aureus species that produces an exfoliative toxin. Presentation includes fever, tender skin, and bullae. Large sheets of skin slough several days after the illness begins, and the Nikolsky sign is present (extension of bullae when pressure is applied to the skin). Management includes good wound care and intravenous antibiotics directed against S. aureus.
  13. Scarlet fever
  14. Definition.Scarlet fever is a toxin-mediated bacterial illness that results in a characteristic skin rash.



  1. Etiology.The cause of infection is strains of GABHS that produce an erythrogenic toxin.
  2. Epidemiology
  3. Peak incidence is in the winter and spring.
  4. Transmission is by large respiratory droplets or by infected nasal secretions.
  5. Clinical features
  6. The exanthem may develop during any GABHS infection (e.g., impetigo, cellulitis, pharyngitis).
  7. Before or during the exanthem, fever, chills, malaise, and often an exudative pharyngitis (see also section V.D) may occur.
  8. The exanthem is characterized by the following:
  9. Begins on the trunkand moves peripherally
  10. Skin is erythematouswith tiny skin-colored papules (scarlatiniform appearance) and has the texture of sandpaper (sandpaper rash). The rash blanches with pressure.
  11. Petechiae are often localized within skin creases in a linear distribution (“Pastia's lines”).
  12. Desquamationof dry skin occurs as the infection resolves.
  13. Diagnosis.The basis of diagnosis is clinical features and a positive throat culture for S. pyogenes (gold standard) or positive rapid streptococcal tests that detect the GABHS antigen.
  14. Management
  15. The goal is to prevent development of rheumatic fever.
  16. Appropriate antibioticsinclude oral penicillin VK, intramuscular benzathine penicillin, or for penicillin-allergic patients, erythromycin or macrolides.
  17. Complications of GABHS infections
  18. Post-streptococcal glomerulonephritismay occur several weeks after streptococcal pharyngitis. Patients present with hypertension and cola-colored urine. Antibiotic therapy does not prevent this complication (see Chapter 11, section IV.F.1).
  19. Rheumatic fever(see Chapter 16, section VI)
  20. Post-streptococcal arthritisis characterized by joint symptoms (without other features of rheumatic fever) that may last for weeks. Antibiotic therapy does not prevent this complication.
  21. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS)is a phenomenon in which patients develop the acute onset ofobsessive-compulsive symptoms or a tic disorder after streptococcal infection. Antibiotic therapy prevents this complication.
  22. Toxic shock syndrome (TSS)
  23. Definition.TSS is a toxin-mediated illness characterized by fever, shock, desquamating skin rash, and multiorgan dysfunction.
  24. Etiology and pathogenesis
  25. S. aureusis the most common organism associated with TSS, although an increase in GABHS -associated TSS has been reported. In the early 1980s, the majority of TSS cases caused by S. aureus were in young women using tampons. However, only 50% of TSS cases are now related to tampon use.



Table 7-5. Diagnostic Criteria for Toxic Shock Syndrome

Diagnostic criteria
(probable case = 5 of 6 criteria; confirmed case = 6 of 6 criteria)
1. Fever > 38.5°C (> 101°F)
2. Hypotension (SBP < 90 mm Hg or < fifth percentile for age)
3. Diffuse macular erythroderma (appears similar to sunburn)
4. Desquamation occurs 10–14 days after onset of illness
5. Multisystem involvement, including three or more of the following:
   a. Gastrointestinal—vomiting, diarrhea, and abdominal pain
   b. Myalgias or elevated creatine kinase levels
   c. Hyperemia of the mucous membranes (e.g., pharyngitis, vaginitis)
   d. Pyuria in the presence of negative urine cultures or elevated blood urea nitrogen and creatinine to twice normal limit
   e. Thrombocytopenia
   f. Central nervous system—altered level of consciousness, meningismus
6. Negative cultures of blood, cerebrospinal fluid, and pharynx (except for positive blood culture for Staphylococcus aureus)

Other clinical findings may include oral ulcers, acute respiratory distress syndrome, headache, edema, conjunctivitis, disseminated intravascular coagulation, elevated transaminases, hypocalcemia, and hypoalbuminemia.
SBP = systolic blood pressure.

  1. Organisms produce toxins (exotoxins and toxic shock syndrome toxin) that result in the clinical features of TSS.
  2. Clinical features and diagnostic criteria (Table 7-5).Patients with TSS may present with a wide variety of signs and symptoms.
  3. Management.Treatment includes supportive measures to reverse shock, anti-staphylococcal antibiotics, and removal of the nidus of infection (tampon) if present. Intravenous immune globulin (IVIG) may have some benefit.
  4. Infection caused by animal and human bites (see Chapter 20, section IX.B, C, D)
  5. Fungal infections of the skin

(see Chapter 19, section V.A)

  1. Viral infections of the skin

(see Chapter 19, section V.C)

  1. Ectoparasitic infections of the skin

(see Chapter 19, section V.D)

  1. Bone and Joint Infections

(see Chapter 17, section III.B)

  1. Diarrhea
  2. Etiology

Diarrheal diseases and resulting dehydration are among the most common causes of childhood morbidity and mortality worldwide. Infection is one of the most common causes of acute diarrhea during childhood. Specific causes of diarrhea include:



  1. Viral causesmost commonly include rotavirus and Norwalk virus.
  2. Rotavirus
  3. Epidemiology. Rotavirus is the most common infectious agent causing gastroenteritis.This RNA virus is usually seen in the winter months and is spread by the fecal-oral route.
  4. Clinical features.Incubation period is 1–3 days. Patients may be asymptomatic, or may have vomiting, diarrhea, and dehydration. Diarrhea is usually self-limited and lasts 4–7 days. Symptoms of URI may sometimes be present.
  5. Diagnosis.A positive stool enzyme-linked immunosorbent assay (ELISA) test is used to make the diagnosis. WBCs are absent from the stool.
  6. Management.Treatment is supportive with particular attention to fluid management and early institution of feedings to prevent gut atrophy. Some children may develop transient lactose intolerance.
  7. Norwalk virus
  8. Epidemiology.Norwalk virus is an RNA virus spread by the fecal-oral route and linked to outbreaks of gastroenteritis in all age groups, particularly in closed populations(e.g., day care centers, schools, cruise ships).
  9. Clinical featuresare similar to those caused by rotavirus with vomiting a prominent symptom. Duration of illness is only 48–72 hours, a shorter duration as compared with the other viral causes.
  10. Diagnosisis based on clinical features.
  11. Managementis supportive.
  12. Bacterial causes, associated clinical features, and management (see Table 7-6)
  13. Parasitic causes(see section XV)
  14. Evaluation

should include a detailed history, complete physical examination, and selective laboratory studies.

  1. Specific historical featuresinclude:
  2. Presence of fever, rash, abdominal pain, vomiting, and blood or mucus in the stool
  3. Recent antibiotic use (e.g., may result in C. difficileinfection)
  4. Day care attendanceor travel
  5. Unusual pets (e.g., lizards and turtles may transmit Salmonellaspecies)
  6. Unusual foods or recent restaurant meal
  7. Physical examinationshould be detailed and focused, especially on assessment of hydration, particularly in young children.
  8. Laboratory studiesmay include CBC, serum electrolytes, and assessment of stool for gross or occult blood (i.e., stool guaiac), WBCs (i.e., Wright stain), ova and parasite evaluation (three separate ova and parasite stool specimens increase the yield) and culture. ELISA may be useful in the detection of rotavirus, Giardia lamblia, and C. difficileinfection.



Table 7-6. Characteristics of Bacterial Causes of Infectious Diarrhea


Clinical Features



Enterotoxigenic Escherichia coli (ETEC)

Major cause of traveler's diarrhea
Generally noninvasive with watery diarrhea

Stool WBCs absent
Diagnosis is made clinically but can be confirmed on culture

Antibiotics (quinolones or sulfonamides in children) may shorten duration of symptoms
Hydration is essential

Enteropathogenic E. coli (EPEC)

Noninvasive watery diarrhea seen in preschoolers

Stool WBCs absent
Diagnosis made on stool culture

Oral sulfonamides or quinolones are indicated
Hydration is essential

Enterohemorrhagic E. coli (EHEC)

Strain 0157:H7 is responsible for hemolytic uremic syndrome (HUS) via endotoxin release

Stool WBCs present
Culture is diagnostic

If HUS is present, antibiotic therapy is avoided(HUS may worsen as a result of enhanced endotoxin release)

Shigella sonnei

Bloody diarrhea predominates
Children may develop seizures
 secondary to neurotoxin release

Stool WBCs present
Culture is diagnostic

Third-generation cephalosporins or fluoroquinolones are indicated

Salmonella species

May cause bloody or nonbloody diarrhea
Spread by fecal-oral route, poultry, milk, eggs, and exposureto lizards or turtles
Patients, especiallythose with sickle celldisease, may developbacteremia orosteomyelitics

Stool WBCs may bepresent or absent
Culture is usually diagnostic

Treatment is not indicated for uncomplicated gastroenteritis in immunocompetent hosts > 3 months of age because it increases carriage time
Treatment for invasive disease includes a third-generation cephalosporin

Campylobacter jejuni

Most common cause of bacterial bloody diarrhea in the U.S.
Disease is often self-limited and is spread by contaminated food (usually poultry)

Stool WBCs are usually present if blood is present Stool culture is diagnostic

Oral erythromycin is indicated but symptoms commonly resolve without antimicrobial intervention

Yersinia enterocolitica

May cause mesenteric adenitis along with gastroenteritis that may mimic acute appendicitis

Stool culture or mesenteric node culture grows the organism

Antibiotics may benefit patients;third-generation cephalosporins are commonly used

Clostridium difficile

A normal component of gut flora that may cause colitis if it overgrows the rest of the gut flora, as is seen after antibiotic use

Diagnosis is made by identifying toxin in the stool
Endoscopy may demonstratepseudomem-branes

Oral or intravenous metronidazole is effective
Oral vancomycin is reserved for resistant cases

Vibrio cholerae

Seen in developing countries
Characterized by watery diarrhea withmassive water loss

Diagnosis is based on history of massive watery diarrhea in a patient returning from or residing in an endemic area
V. cholerae may be cultured from stool, but this is not routinely performed in the U.S.
Serologic diagnosis is available from the Centers for Disease Control and Prevention

Fluid replacement is critical
Antibiotics may shorten the duration but are generally not used

WBCs = white blood cells.




  1. The classic electrolyte findingis a non–anion gap hyperchloremic metabolic acidosis as a result of bicarbonate loss in the stool.
  2. In general, the presence of either gross or occult blood in stools predicts the presence of stool WBCs.
  3. The utility of a culture when WBCs are absent in the stool is low.
  4. Management principles
  5. Fluid management is the cornerstone of therapy.
  6. Antibioticsare indicated for only a few causes of diarrhea (Table 7-6).

XII. Urinary Tract Infections

(see Chapter 11, section XIII)

XIII. Specific Viral Infections

  1. Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS)
  2. Epidemiology.More than 10, 000 children and adolescents in the United States are reported to be infected with HIV, although this is considered to be an underestimate. Worldwide, more than 1 million children have AIDS, and as many as 10 times this number are infected with HIV.
  3. Transmission
  4. Perinatal transmission currently accounts for > 95% of pediatric HIV cases.
  5. In utero, intrapartum, or postpartum(through breastfeeding) transmission of HIV from an infected mother to her infant may occur. Transmission rates range from 5% in the United States, because of the common use of antiretroviral therapy during pregnancy, to 50% in the developing world.



  1. Factors that increase the risk of transmission:
  2. High maternal viral load (as measured by number of RNA copies)
  3. Advanced maternal HIV disease
  4. Primary maternal HIV infection
  5. Concomitant maternal genital infections, including chorioamnionitis
  6. Premature birth
  7. Prolonged rupture of membranes
  8. Factors that decrease the risk of transmission:
  9. Undetectable maternal viral load
  10. Cesarean section
  11. Adherence to maternal antiretroviral therapy and infant postexposure prophylaxis
  12. Other modes of HIV transmission:
  13. Sexual contact, an important mode of infection in adolescents
  14. Blood producttransmission, which is now rare because of mandatory blood product screening
  15. Sharing of intravenous and tattoo needles
  16. Clinical features
  17. Most infants with perinatally acquired HIV infection are asymptomaticfor the first year of life.
  18. Early symptoms of HIV infection:
  19. Failure to thrive
  20. Thrombocytopenia
  21. Recurrent infections, such as otitis media, pneumonia, and sinusitis
  22. Lymphadenopathy
  23. Parotitis
  24. Recurrent, difficult-to-treat thrush
  25. Loss of developmental milestones
  26. Severe varicella infection or zoster
  27. Diagnosis
  28. All infants born to HIV-infected mothers have transplacentally acquired maternal antibody that may persist for as long as 18–24 months.
  29. HIV-specific DNA PCRis performed at birth and monthly until 4 months of age to detect infants who are infected perinatally.
  30. Negative HIV-specific DNA PCR at 4 months is consistent with an infant who has not been infected.If the DNA PCR is negative for HIV, infants are followed until they lose their transplacentally acquired maternal antibody (by age 18–24 months).



  1. Management
  2. Infants born to HIV-infected mothers should be tested for the presence of virus, as outlined above in section XIII.A.4, in addition to:
  3. Zidovudine for 6 weeks for postexposure prophylaxis
  4. Trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis cariniipneumonia (PCP) prophylaxis until HIV DNA PCR at age 4 months is negative
  5. No breastfeeding
  6. Urine CMV culture to detect coinfection with CMV (occurs in 5%)
  7. HIV-infected childrenshould ideally be managed at an institution experienced in the care of children with HIV. Treatment includes administration of medications as well as nutrition and social work services and regular neurodevelopmental testing.
  8. All HIV-infected infants and all symptomatic children should receive antiretroviral agentsthat may include nucleoside reverse transcriptase inhibitors (NRTIs), non–nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors. Combination therapy is the cornerstone of treatment to avoid selection of resistant viruses.Close monitoring is essential because medications may cause bone marrow suppression, hepatitis, and pancreatitis.
  9. Prophylaxis for opportunistic infections is important.The decision to begin prophylaxis is based on the patient's age and CD4 count.
  10. Immunizationsand usual well child care are critical. HIV-infected children should receive all routine childhood vaccines except the live varicella vaccine. The measles, mumps, and rubella (MMR) vaccine, although a live viral vaccine, is currently recommended for all but the most severely immunocompromised HIV-infected children. Annual influenza vaccine, pneumococcal vaccine, and annual tuberculin skin testing are all recommended.
  11. Regular monitoring of T-cell subsets and HIV RNA PCR to assess viral load
  12. Annual ophthalmologic examination to assess for CMV retinitis in HIV-infected children who are CMV antibody positive
  13. Complications of HIV infection
  14. Opportunistic infections
  15. PCP
  16. Epidemiology
  17. Most common opportunistic infection in HIV-infected children
  18. Risk of infection correlates with CD4 cell number and percentage.
  19. Clinical features.Fever, hypoxia, and interstitial pulmonary infiltrates are present.
  20. Management.Prophylaxis against PCP infection is with oral TMP/SMX. Treatment of PCP infection may include TMP/SMX, pentamidine, or atovaquone.



  1. M. aviumcomplex (MAC). MAC is characterized by fever, weight loss, night sweats, abdominal pain, bone marrow suppression, and elevated liver transaminases. Risk is highest when the CD4 count falls to less than 50 cells/mm3.
  2. Fungal infections.Candidal infections (e.g., thrush, esophagitis), cryptococcal infections (e.g., meningitis, pneumonia), histoplasmosis, coccidioidomycosis, and aspergillosis may occur.
  3. Viral infections.CMV (e.g., retinitis, esophagitis, colitis), HSV, and varicella zoster virus (VZV) may occur.
  4. Parasitic infections.Toxoplasmosis and infections caused by Cryptosporidium and Isospora belli may occur.
  5. Lymphoma, especially B cell, caused by EBV.
  6. Prognosis.The expanded testing of pregnant women for HIV, coupled with aggressive prenatal antiretroviral therapy, has dramatically reduced the perinatal HIV transmission rate in the United States. Morbidity and mortality of HIV-infected children have also declined, correlating with the licensure of new antiretroviral agents, especially protease inhibitors.
  7. Infectious Mononucleosis
  8. Etiology and epidemiology
  9. EBV, a member of the herpes virus family, is the major etiologic agent.EBV is commonly acquired during adolescence, although infection also often occurs in young children. EBV is transmitted primarily by saliva and seems to infect the B lymphocyte.
  10. Other agents, including toxoplasmosis, CMV, and HIV, may cause a similar clinical syndrome.
  11. Clinical features
  12. Young children may be asymptomatic.
  13. Older children develop typical signs and symptoms.
  14. Fever, which may last up to 2 weeks
  15. Malaise and fatigue
  16. Pharyngitis(typically exudative, resembling GABHS pharyngitis)
  17. Posterior cervical lymphadenopathy(lymphadenopathy may also be diffuse)
  18. Hepatosplenomegaly.Spleen is enlarged in 80%.
  19. A minority of patients may also develop a macular or scarlatiniform rash.
  20. Symptoms resolve in weeks to months.
  21. Diagnosis
  22. CBCmay demonstrate atypical lymphocytes. Other laboratory abnormalities include neutropenia, thrombocytopenia, and elevated transaminases.



  1. Monospotis a first-line test in diagnosing EBV infectious mononucleosis. A monospot measures the presence of heterophile antibody, the ability to agglutinate sheep red blood cells (RBCs). It has an overall sensitivity of 85% but is less sensitive in children under 4 years of age because these antibodies do not reliably form in younger children. CMV causes the majority of monospot-negative cases of infectious mononucleosis in older children.
  2. EBV antibody titers are the preferred method of diagnosing EBV infection in children younger than 4 years of age.
  3. To diagnose EBV, antibodies to viral capsid antigen (VCA), early antigen (EA), and Epstein-Barr nuclear antigen (EBNA)are tested.
  4. Acute infection is diagnosed by finding elevated levels of IgM–VCAand absent antibodies to EBNA. Antibodies to EBNA are detected 2–3 months after acute infection.
  5. PCRtesting may also be used for diagnosis.
  6. Management.Therapy for most cases of EBV infection is supportive. Corticosteroids are sometimes used for severe pharyngitis.
  7. Complications
  8. Neurologic complications, including cranial nerve palsies and encephalitis
  9. Severe pharyngitis, which may cause upper airway obstruction
  10. Amoxicillin-associated rash.Patients with EBV infection who are misdiagnosed with GABHS pharyngitis and prescribed amoxicillin often develop a diffuse pruritic maculopapular rash 1 week after starting the antibiotic. This is not an allergic reaction but is idiosyncratic.
  11. Splenic rupture.Children with infectious mononucleosis with splenomegaly should be restricted from contact sports until the spleen has returned to normal size.
  12. Malignancy.EBV has been isolated from nasopharyngeal carcinoma and Burkitt's lymphoma. EBV may also result in lymphoproliferative disease, a lymphomalike illness, in immunosuppressed patients.
  13. Measles
  14. Etiology.Measles is also known as rubeola and 10-day measles and is caused by an RNA virus of the Paramyxoviridae family.
  15. Epidemiology
  16. Owing to routine measles vaccination, the incidence of measles has declined in the United States during the past 40 years, with fewer than 100 cases per year now reported.
  17. Measles is highly infectiousand spreads easily among susceptible individuals in households and schools.
  18. Clinical features.Manifestations develop after an 8- to 12-day incubation period. Clinical features include a classic clinical prodrome, followed by a transient enanthem (rash on mucous membranes) and a characteristic exanthem (rash on the skin).



  1. The three C's(c oughc onjunctivitis, and c oryza) is a mnemonic to help remember the classic prodrome. Other early symptoms include photophobia and low-grade fever.
  2. The enanthemis characterized by Koplik spots, small gray papules on an erythematous base located on the buccal mucosa. Koplik spots are pathognomonic of measles and are present before the generalized exanthem. They are transient and may be absent by the onset of other clinical features.
  3. The exanthemis characterized as an erythematous maculopapular eruption that begins around the neck and ears and spreads down the chest and upper extremities during the subsequent 24 hours. The exanthem covers the lower extremities by the second day, becomes confluent by the third day, and lasts for 4–7 days.
  4. Fever, usually > 101° F (> 38.3°C) accompanies the onset of symptoms.
  5. Complications
  6. Bacterial pneumonia is the most common complication and the most common cause of mortality.
  7. Otitis media is also common.
  8. Laryngotracheitis
  9. Encephalomyelitis(i.e., inflammation of both the brain and spinal cord)
  10. Subacute sclerosing panencephalitisis a rare late complication.
  11. Diagnosis.The basis of diagnosis is clinical features and confirmation of measles infection by serologic testing.
  12. Management
  13. Supportive care is most important.
  14. Vitamin Ahas been shown to improve outcome.
  15. Immunoglobulin can be used for postexposure prophylaxis in high-risk individuals (e.g., children with HIV and other immunodeficiency states) who are exposed to measles.
  16. Rubella
  17. Etiology.Rubella, which is also known as German measles or 3-day measles, is caused by an RNA virus in the togavirus family.
  18. Epidemiology.Like measles, the incidence of rubella has declined during the past 40 years as a result of routine immunization during childhood. Rubella is also highly infectious.
  19. Clinical features.Unlike measles, rubella is mild and often asymptomatic. Incubation period is 14–21 days.
  20. The prodromeincludes mild upper respiratory symptoms and low-grade fever.
  21. Painful lymphadenopathy, especially of the suboccipital, posterior auricular, and cervical nodes
  22. The exanthemfollows the adenopathy and is characteristically nonpruritic, maculopapular, and confluent. It begins on the face, spreads to the trunk and extremities, and lasts 3–4 days.



  1. The fever is usually mild (< 101° F or < 38.3°C) and accompanies the other clinical symptoms.
  2. Complications
  3. Meningoencephalitis
  4. Polyarteritisis seen primarily in teenage girls and young women and may last several weeks.
  5. Congenital rubella syndrome (CRS)is the most serious complication of an otherwise relatively benign disease.
  6. CRS occurs after primary maternal infection during the first trimester. Fetal anomalies occur in 30–50% of infected fetuses.
  7. Presenting clinical featuresinclude thrombocytopenia, hepatosplenomegaly, jaundice, and purpura (“blueberry muffin baby”).
  8. Structural abnormalitiesinclude congenital cataracts and patent ductus arteriosus. Other findings include sensorineural hearing loss and meningoencephalitis.
  9. Late complicationsmay include mental retardation, hypertension, type 1 diabetes mellitus, and autoimmune thyroid disease.
  10. Diagnosisis by viral culture and by serology.
  11. Managementis supportive.
  12. Hepatitis

(see Chapter 10, section XI.E)

  1. Varicella

(see Chapter 19, section V.C.6)

XIV. Specific Fungal Infections

  1. Aspergillosis

Aspergillus species are ubiquitous molds that cause both invasive disease and noninvasive allergic disease.

  1. Invasive diseaseoccurs in severely immunocompromised patients, such as recipients of bone marrow or solid organ transplant. Management includes high-dose systemic antifungal therapy with amphotericin B and often surgery to resect the aspergilloma, a tumorlike mass formed by the fungus. Prognosis is poor.
  2. Allergic bronchopulmonary aspergillosisis characterized by wheezing, eosinophilia, and pulmonary infiltrates. It occurs most commonly in patients with chronic lung disease (e.g., cystic fibrosis). Patients have elevated aspergillus-specific immunoglobulin E levels, and management includes corticosteroids and, in some cases, antifungal therapy.
  3. Candidiasis
  4. Epidemiology and etiology.Candida species, especially C. albicans, are present on the skin and throughout the gastrointestinal tract.
  5. In immunocompetent individuals, overgrowth of yeast may occur normally or under the influence of systemic antibiotics, causing mild superficial infection.



  1. In immunocompromised individuals, overgrowth of yeast may occur readily, causing severe invasive infection.
  2. Clinical features and management
  3. Overgrowth of Candidaon the skin or mucous membranes may lead to diaper dermatitis, oral thrush, or vulvovaginal candidiasis. Treatment includes topical antifungal therapy.
  4. Invasive candidal infections in immunocompromised patients may include fungemia, meningitis (see Table 7-3 for CSF profile), osteomyelitis, and endophthalmitis. Treatment includes systemic antifungal therapy.
  5. Coccidioidomycosis
  6. Etiology.C. immitis is a fungus found in the soil in the southwestern United States and Mexico.
  7. Clinical features
  8. Infection occurs when Coccidioidesis inhaled into the lungs.
  9. Most infections are asymptomaticor cause a mild pneumonia.
  10. African Americans, Filipinos, pregnant women, neonates, and immunocompromised individuals are at highest risk for disseminated disease, which may include severe pneumonia, meningitis, and osteomyelitis.
  11. Management.Mild pulmonary disease in immunocompetent patients generally does not require treatment. Disseminated disease and illness in immunocompromised hosts are treated with systemic antifungal therapy.
  12. Cryptococcal infection
  13. Etiology.Cryptococcus neoformans is a yeast found in the soil.
  14. Clinical features
  15. Infection is acquired when Cryptococcusis inhaled into the lungs.
  16. Most infections are asymptomatic.
  17. Spread to the central nervous system (CNS) occurs primarily in immunocompromised patients. Cryptococcal meningitis is one of the AIDS-defining illnesses.
  18. Disseminated infection, including infection of the bones, joints, and skin, may also occur in immunocompromised hosts but is rare in children.
  19. Management.Treatment of disseminated and CNS cryptococcal infection includes systemic antifungal therapy.
  20. Specific Parasitic Infections
  21. Amebiasis
  22. Etiology.Infection is by the protozoan Entamoeba histolytica. Infection is acquired by ingestion of the cyst in contaminated food or water. Symptoms begin 1–4 weeks later as the trophozoite form emerges from the cyst and invades the colonic mucosa.
  23. Epidemiology.Amebiasis is present worldwide with the highest incidence in developing nations.



  1. Clinical features
  2. Most patients are asymptomatic.
  3. Symptomatic intestinal diseaseranges from mild colitis to severe dysentery. Young children, pregnant women, and immunocompromised patients have more severe disease.
  4. Symptomsinclude cramping abdominal pain, tenesmus, and diarrhea that may contain blood or mucus. Weight loss, fever, tender hepatomegaly, chest pain, right shoulder pain, respiratory distress, and jaundice may also occur.
  5. Abdominal complicationsinclude intestinal perforation, hemorrhage, strictures, and a local inflammatory mass or ameboma.
  6. Extraintestinal amebiasismanifests as an abscess, most commonly in the liver, although it may form in the brain, lung, or other organs.
  7. Diagnosis.Identification of the trophozoites or cysts in the stool is diagnostic. Colonoscopy with biopsy or serum antibody assays may also be helpful. Ultrasound or CT scan can identify an abscess in the liver or other organs.
  8. Management.Treatment is based on the site of involvement and includes elimination of both the invading organism and those within the intestinal lumen. Metronidazole is themainstay of therapy and is recommended along with a luminal amebicide, such as iodoquinol.
  9. Giardiasis
  10. Etiology.Infection is by the protozoan G. lamblia. Infection occurs by fecal-oral contamination when the cyst is accidentally ingested.
  11. Epidemiology.Giardiasis occurs worldwide. Travelers to Russia and individuals who drink contaminated mountain water in the western United States are at higher risk.Giardiasis may occur as endemic disease or as large waterborne or day care center outbreaks. It may also be transmitted by person-to-person spread or from animals, such as dogs and cats.
  12. Clinical features.Signs and symptoms are variable and range from asymptomatic disease to explosive diarrhea. Symptoms occur 1–2 weeks after ingestion of the cyst and may persist for 2–6 weeks.
  13. Infection localizes within the small bowel, causing diarrheathat is typically described as voluminous, watery, and foul-smelling.
  14. Abdominal pain, cramping, bloating, flatulence, weight loss, and low-grade fever may also occur.
  15. Diagnosis. Direct examinationof stool for cysts and trophozoites or by stool ELISA tests are used to make the diagnosis. Small bowel biopsy is sometimes indicated in difficult-to-diagnose cases.
  16. Management.Treatment includes metronidazole or furazolidone.
  17. Malaria
  18. Etiology.Malaria is an obligate intracellular bloodborne parasitic infection caused by four species of Plasmodium : P. falciparum (responsible for the most severe disease), P. vivax, P. malariae, and P. ovale.



  1. Epidemiology
  2. Malaria is the most important parasitic cause of morbidity and mortality in the world, responsible for 2–3 million deaths each year, mostly in young children.
  3. Malaria is endemic in tropical and subtropical regions of the world. The risk of malariais high for travelers to these endemic areas.
  4. Transmissionof Plasmodium occurs via the bite of the infected female Anopheles mosquito, a night-biting mosquito.
  5. Clinical features
  6. Initial findingsinclude vague flulike symptoms that typically include headache, malaise, anorexia, and fever.
  7. Cyclical feversfollow the flulike prodrome and occur every 48–72 hours; they correlate with RBC rupture and subsequent parasitemia. Chills, vomiting, headache, and abdominal pain may also occur.
  8. Other featuresinclude hemolytic anemia, splenomegaly, jaundice, and hypoglycemia. Cerebral malaria, renal failure, shock, and respiratory failure all may occur.
  9. Diagnosis.Identification of the parasite on thin and thick Giemsa-stained peripheral blood smears is diagnostic. The thick smear is for malarial screening, and the thin smear is for malarial identification and staging (determination of the level of parasitemia) of the particular Plasmodium species.
  10. Management.Choice of antimalarial therapy is based on resistance patterns, species type, and severity of illness. Medications include chloroquine, quinine, quinidine gluconate, mefloquine, and doxycycline.
  11. Prevention
  12. Avoidance of mosquito bites is the mainstay of prevention.DEET (N, N -diethyl-m -toluamide)-containing repellants, insecticide-impregnated bed nets, and protective clothing are essential.
  13. Chemoprophylaxis, which may include oral chloroquine, mefloquine, doxycycline, or atovaquone and proguanil hydrochloride (dependent on the area visited and itsPlasmodiumspecies and resistance patterns).
  14. Control of theAnopheles mosquito is important for individuals living in endemic areas.
  15. Toxoplasmosis
  16. Etiology.Infection is by the intracellular parasite T. gondii.
  17. Epidemiology. Transmissionoccurs through direct contact with cat feces (the cat is the definitive host for the parasite), ingestion of undercooked meat, fruits, or vegetables contaminated with cysts, transplacental passage, exposure to contaminated blood products, or organ transplantation.
  18. Clinical features
  19. Most patients are asymptomatic.
  20. Symptoms, if present, include a mononucleosis-like illnessconsisting of malaise, fever, sore throat, myalgias, and lymphadenopathy. Rash and hepatosplenomegaly may be present. Symptoms are self-limited and generally benign.



  1. Reactivation of disease may occurif patients become immunosuppressed. In this situation, the symptoms are often more severe and may include encephalitis, focal brain lesions, pneumonitis, or, rarely, disseminated disease. Toxoplasmosis is an important opportunistic infection in HIV-infected patients, and patients commonly present with focal seizures.
  2. Ocular toxoplasmosismay occur. T. gondii is the most common cause of infectious chorioretinitis.
  3. Congenital toxoplasmosisis characterized by the triad of hydrocephalus, intracranial calcifications, and chorioretinitis.
  4. Diagnosis.Serologic testing, PCR, or identification of the organism in cultures of amniotic fluid, CSF, or blood are used for diagnosis.
  5. Management.Most infections do not require specific therapy. Treatment is indicated for infants with congenital toxoplasmosis, pregnant women with acute toxoplasmosis, and immunocompromised individuals with reactivation resulting in toxoplasma encephalitis. Treatment includes sulfadiazine and pyrimethamine.
  6. Prevention. Pregnant women and immunocompromised individuals are at highest risk.Therefore, they should avoid cat feces and undercooked meats and should clean all fruits and vegetables before consumption. Gloves should be used when gardening or preparing meat.

XVI. Specific Helminth Infections

  1. General Concepts (characteristics of specific infections are noted in Table 7-7)
  2. Groups at highest riskinclude immigrants, travelers, and homeless individuals.
  3. Common clinical features
  4. Most infections are asymptomatic.
  5. Abdominal symptomsinclude pain, anorexia, nausea, rectal prolapse, and obstruction.
  6. Diagnosisis usually made by three separate stool examinations for ova and parasites. To detect pinworms, a cellulose tape test may be performed; the tape is placed sticky side down on the perianal region before sleep and is removed immediately on awakening and examined for eggs.
  7. Cysticercosis
  8. Epidemiology
  9. Worldwide distributionwith high incidence in Mexico and Central America
  10. In endemic areas, 20–50% of cases of epilepsy are caused by cysticercosis.



Table 7-7. Characteristics of Specific Helminth Infections



Clinical Features


Enterobius vermicularis(pinworm)

Most common helminthic infection in the U.S.
Fecal-oral transmission of eggs
Preschool and school-age children

Anal or, less commonly, vulvar pruritus
Insomnia, anorexia, enuresis, nighttime teeth-grinding

Single dose of mebendazole, albendazole, or pyrantel pamoate
Treat all close contacts

Ascaris lumbricoides(roundworms)

Largest and most common intestinal roundworm
Fecal-oral transmission of eggs

Löffler syndrome—transient pneumonitis as larvae migrate through lungs causing fever, cough, wheezing, and eosinophilia
Small bowel obstruction

Mebendazole, albendazole, or pyrantel pamoate
Screen all close contacts

Trichuris trichiura(whipworm)

Worldwide distribution Often seen in association with Ascaris infection

Most are asymptomatic
Abdominal pain, tenesmus, bloody diarrhea, rectal prolapse

Mebendazole, albendazole, or pyrantel pamoate
Screen all close contacts

Necator americanus andAncylostoma duodenale(hookworm)

Rural, tropical, and subtropical areas where soil is contaminated with human feces
Percutaneous infection through a bare foot; larvae migrate to lungs and are coughed up and then swallowed

Rash and pruritus at site of penetration
Iron-deficiency anemia with fatigue, pallor, and failure to thrive

Mebendazole, albendazole, or pyrantel pamoate
Screen close contacts
Iron supplementation

Strongyloides stercoralis

Tropics, subtropics, and southern and southwestern U.S.
Life cycle same as hookworm

Transient pruritic papules at site of penetration
Gastrointestinal symptoms

Ivermectin, thiabendazole, or albendazole

Cutaneous larva migrans

Intradermal migration of dog or cat hookworms
Contact with feces-contaminated soil

Migrating, pruritic, serpiginous, erythematous tracks on skinSelf-limited, lasting weeks to months

Resolves without treatment in most cases
Ivermectin, thiabendazole, or albendazole for severe disease

Toxocara canis or cati (toxocariasis or visceral larva migrans—VLM)

Most common in children 1–4 years who have pica
Ingestion of eggs in contaminated soil or dog fur
Larvae released from eggs and migrate through tissues

Generalized VLM: fever, eosinophilia, leukocytosis, hepatomegaly; may have malaise, anemia, cough, myocarditis
Ocular larva migrans: retinal granulomas or endophthalmitis

Albendazole or mebendazole
Steroids may also be used for ocular involvement



  1. Etiology.Infection occurs via the fecal-oral route when the eggs of Taenia solium, the pork tapeworm, are accidentally ingested.
  2. Clinical features
  3. No symptoms are present until the tapeworm encysts in muscle, subcutaneous tissue, or brain.
  4. Subcutaneous nodulesmay be palpated or seen as calcifications on radiography.
  5. Neurocysticercosis
  6. The fourth ventricleis the most common site of involvement, although brain parenchyma, meninges, spine, or eyes may be affected.
  7. Signs and symptomsinclude seizures (presenting symptom in 70% of cases), hydrocephalus, and stroke.
  8. Diagnosis
  9. Ova and parasite stool evaluationdetects the Taenia eggs in only 25% of cases.
  10. Serology is available in some laboratories.
  11. Head CT or MRI scansmay show a solitary parenchymal cyst or single or multiple calcifications. Calcified lesions represent areas of old, nonviable parasitic infection.
  12. Management.Antiparasitic medications are reserved for individuals infected with the adult tapeworm. Those with neurocysticercosis with brain imaging that shows only calcified lesions require only anticonvulsant therapy.

XVII. Miscellaneous Infections

  1. Rickettsial Infections
  2. Lyme disease(see Chapter 16, section VII)
  3. Rocky mountain spotted fever (RMSF)
  4. Etiology.RMSF is caused by Rickettsia rickettsii, a Gram-negative intracellular coccobacillus that is transmitted by the bite of a tick.
  5. Epidemiology
  6. RMSF is endemic across the United States but occurs primarily in the southeastern regions of the United States.
  7. Incidence is highest in school-age children, and infection usually occurs in the spring and summer.
  8. Fewer than 50% of patients recall a tick bite.
  9. Clinical features.Symptoms and signs range from mild to life-threatening and may include:
  10. Fever
  11. Petechial rashthat begins on the extremities (ankles and feet) and moves in a caudal and centripetal direction (i.e., wrists and hands and then to trunk and head)
  12. Myalgias



  1. Hepatosplenomegaly and jaundice
  2. CNS symptoms, such as headache, coma, and seizures
  3. Hypotension
  4. Laboratory findings. Thrombocytopenia, elevated transaminases, and hyponatremiamay occur. CSF findings may show an aseptic meningitis picture (see Table 7-3).
  5. Diagnosis.The diagnosis is made clinically but should be confirmed with serologic tests for Rickettsia.
  6. Management.Treatment includes oral or intravenous doxycycline and supportive care. Antibiotics are usually started empirically on the basis of clinical presentation before the results of diagnostic testing, given the possibility of significant morbidity and mortality in untreated infection.
  7. Prevention.Methods include tick avoidance and prompt tick removal. Prophylactic antibiotics after tick bites are not indicated.
  8. Ehrlichiosis (human monocytic ehrlichiosis and human granulocytic ehrlichiosis)
  9. Etiology.Ehrlichiosis is caused by Ehrlichia chaffeensis, which is transmitted by the bites of several tick species.
  10. Epidemiology.Most cases occur in the spring and summer in the same regions as RMSF.
  11. Clinical features.Ehrlichiosis is often referred to as “spotless RMSF” because it has many of the same symptoms as RMSF but usually no rash. Symptoms include fever, headache, myalgias, and lymphadenopathy.
  12. Laboratory findings.These are similar to those seen in RMSF (see section XVII.A.2.d).
  13. Diagnosis.The diagnosis is confirmed by serology and PCR technology in some laboratories.
  14. Management.Treatment includes doxycycline and supportive care.
  15. Cat Scratch Disease
  16. Etiology.Cat scratch disease is caused by the Gram-negative bacteria Bartonella henselae.
  17. Clinical features
  18. Regional lymphadenopathy(especially in the axillary, cervical, or inguinal region), distal to and after a cat or kitten scratch, is the most common presentation.
  19. The initial scratch results in a papule along the line of the scratch, followed by lymphadenopathy 1–2 weeks later.
  20. The involved lymph node is commonly erythematous, warm, and tender. Suppuration occurs in approximately 10%.
  21. Fevermay occur in one third of patients.
  22. Less common findingsinclude Parinaud oculoglandular syndrome (conjunctivitis and preauricular lymphadenitis), encephalitis, osteomyelitis, hepatitis, pneumonia, and hepatic or splenic lesions.
  23. Diagnosis.Serology that demonstrates elevated serum IgM antibody to B. henselae is diagnostic.



  1. Management.Treatment usually consists of supportive care. Antibiotics are generally reserved for patients with systemic disease or immunodeficiency. Antibiotics used include oral azithromycin, TMP/SMX, and ciprofloxacin. Surgery is not indicated and may result in persistent fistulous tracks.
  2. Tuberculosis (TB)
  3. Etiology.The cause of TB is Mycobacterium tuberculosis.
  4. Categories
  5. Exposureis the term used to describe an individual who has been in recent contact with an individual with contagious pulmonary TB. Physical examination, tuberculin skin test, and chest radiograph are all normal.
  6. Latent tuberculosis infection (LTBI)is the term used to describe an asymptomatic individual with a positive tuberculin skin test, normal physical examination, and a chest radiograph that either is negative or shows only pulmonary granulomas or calcifications with or without regional lymph nodes.
  7. Tuberculosis diseaseis the term used to describe an individual with signs and symptoms of TB with or without positive findings on chest radiograph (see section XVII.C.5). Disease may be pulmonary or extrapulmonary.
  8. Epidemiology
  9. TB is most common among urban, low-income, and minority groups, although it may be seen in children of any socioeconomic status.
  10. Those at highest riskinclude immigrants from highly endemic regions of the world, health care personnel, homeless individuals, residents of institutions or correctional facilities, and individuals with immunodeficiency conditions (e.g., HIV, chronic disease, immunosuppressive medications).
  11. Transmissionof TB occurs by inhalation of small airborne droplets from an individual with contagious pulmonary TB. Children younger than 12 years of age are generally not contagious because their cough is minimal and their pulmonary lesions are usually small.
  12. Clinical features
  13. In LTBI, most children with a positive tuberculin skin test are asymptomatic and do not progress to TB disease. Infants younger than 12 months of age are at greatest risk of developing disease.
  14. Symptoms of TB diseaseinclude fever, chills, weight loss, cough, and night sweats.
  15. Extrapulmonary TB diseasemay include:
  16. Cervical lymphadenitis (scrofula), the most common form of extrapulmonary TB disease in children
  17. Meningitis(for CSF findings, see Table 7-3)
  18. Abdominal involvement (ileitis)
  19. Skin and joint involvement



  1. Skeletal disease, which may involve the vertebrae (Pott's disease)
  2. Disseminated or miliary disease
  3. Radiographic features of TB disease
  4. Hilar or mediastinal lymphadenopathy
  5. Ghon complex—small parenchymal infiltrate with enlarged hilar lymph nodes
  6. Lobar involvement, pleural effusion, or cavitary disease, which typically affects the upper lung segments.
  7. Diagnosis.Diagnosis and categorization of TB infection is based on an individual's risk factor for infection, tuberculin skin test findings, chest radiographic findings, and culture.
  8. Tuberculin skin test or Mantoux skin testcontains 5 tuberculin units of purified protein derivative (PPD).
  9. It is administered intradermally and read 48–72 hours later by health care personnel trained in interpretation.
  10. The tuberculin skin test becomes positive 2–12 weeks after exposure.
  11. A positive tuberculin skin test is identified by measuring the area of induration(not erythema) and is interpreted on the basis of clinical and individual risk factors:
  12. ≥ 5 mmis considered positive in children who have had close contact with an individual with TB disease, who have clinical or chest radiographic findings consistent with TB disease, or who are immunocompromised.
  13. ≥ 10 mmis considered positive if children are younger than 4 years of age, have a chronic medical condition, or live in an area endemic for TB.
  14. ≥ 15 mmis considered positive in children older than 4 years of age who do not have other risk factors.
  15. Definitive diagnosisinvolves the following:
  16. Positive culturefor M. tuberculosis from early morning gastric aspirates obtained by a nasogastric tube (gastric aspirate samples are preferred for diagnosis in children because children are generally unable to cough up sputum for culture but instead swallow the sputum into the stomach), pleural fluid, CSF, or other body fluids.
  17. Positive staining of fluid for acid-fast bacilli (AFB)
  18. Positive histology(caseating granulomas) from a biopsy specimen
  19. Management.Treatment is based on the TB category.
  20. Patients with LTBIare treated with isoniazid (INH) for 9 months. Older adolescents, pregnant adolescents, and adults are also given daily pyridoxine (vitamin B6) to prevent neurologic complications of INH therapy.
  21. Patients with TB disease are treated on the basis of the location of TB disease and the susceptibility pattern of the organism. Treatment generally includes 2 months of INH, rifampin, and pyrazinamide, followed by 4 months of INH and rifampin.



Review Test

  1. A 13-day-old male infant presents with a fever (temperature to 100.6° F [38.1° C]), mild irritability, and diminished appetite. His parents report no change in the number of wet diapers. Which of the following statements regarding this patient's management or prognosis is correct?

(A) Careful observation at home is appropriate because of the relatively low fever and normal urine output.

(B) The risk of bacteremia in this patient is approximately 25%.

(C) Intramuscular ceftriaxone and close home monitoring are appropriate after evaluation with a complete blood count, blood culture, urinalysis, and urine culture.

(D) Irrespective of the results of initial laboratory testing, management should include intravenous antibiotics and hospitalization.

(E) Bacteria likely to cause fever in this patient include Streptococcus pneumoniae and Haemophilus influenzae type b.

  1. A 7-month-old female infant presents with a fever (temperature to 103.5° F [39.7° C]) for the past 2 days. She was previously healthy. Her parents report no symptoms other than the fever. On examination, she is well hydrated and appears nontoxic, and no focus of infection is identified. Which of the following is the next appropriate management step?

(A) Complete blood count (CBC) and blood culture; if the white blood count (WBC) is normal, home observation is indicated.

(B) Urine culture, urinalysis, CBC, and blood culture; if the WBC is $ 15, 000 cells/mm3, empiric intramuscular ceftriaxone should be administered.

(C) No laboratory studies are indicated because the patient appears nontoxic.

(D) Hospitalization and empiric intravenous cefotaxime

(E) CBC, blood culture, urinalysis, urine culture, lumbar puncture, and chest radiograph; intramuscular ceftriaxone should be given because of the high risk of bacteremia.

  1. A 2-year-old girl presents with fever. On examination, she has exudative pharyngitis, enlarged posterior cervical lymph nodes, and splenomegaly. Which of the following statements regarding her evaluation and management is correct?

(A) Amoxicillin should be prescribed after throat culture for suspected “strep throat.”

(B) Monospot testing is highly sensitive and is the best test to make a diagnosis in this case.

(C) Human immunodeficiency virus is the most likely cause of this infection.

(D) Amoxicillin may result in a pruritic rash in this patient.

(E) Supportive care will lead to rapid improvement and resumption of full activity.

  1. A 6-year-old girl is sent home from summer camp with a fever of 101.3° F (38.5° C), stiff neck, photophobia, and headache. Lumbar puncture in the emergency department reveals the following results: white blood count 380 cells/mm3, with 65% polymorphonuclear cells and 35% lymphocytes; normal protein and glucose; and negative Gram stain. Which of the following pathogens is the most likely cause of her meningitis?

(A) Neisseria meningitidis

(B) Streptococcus pneumoniae

(C) Enterovirus

(D) Borrelia burgdorferi

(E) Mycobacterium tuberculosis



  1. A previously healthy 18-month-old girl is admitted to the hospital with fever (temperature to 102.8° F [39.3° C]), vomiting, and lethargy. She was well until 2 days ago, when she was diagnosed with a viral upper respiratory infection. Lumbar puncture to evaluate the cerebrospinal fluid shows the following results: white blood cells 3, 050 cells/mm3, with 98% polymorphonuclear cells; very low glucose; and elevated protein. Gram stain shows Gram-positive diplococci. Initial management should include which of the following?

(A) Vancomycin and third-generation cephalosporin

(B) Third-generation cephalosporin alone

(C) Ampicillin and third-generation cephalosporin

(D) Third-generation cephalosporin and acyclovir

(E) Third-generation cephalosporin and corticosteroids

  1. A 25-year-old woman is pregnant with her first child. The woman has human immunodeficiency virus (HIV) infection that was diagnosed 2 years before this pregnancy. Which of the following has been shown to increase her risk of transmitting HIV to her infant?

(A) Treatment with highly active antiretroviral therapy during pregnancy and before delivery

(B) Exclusive bottle formula feeding

(C) Prolonged rupture of membranes

(D) Birth by cesarean section

(E) Orally administered zidovudine given to the infant after birth

  1. An 8-year-old girl presents with sore throat, fever, and a rough sandpaper-like rash over her trunk and extremities. A throat culture is positive for group A β-hemolytic streptococcus. Treatment of her infection with antibiotics will prevent which of the following complications?

(A) Reactive arthritis

(B) Rheumatic fever

(C) Post-streptococcal glomerulonephritis

(D) Guillain-Barré syndrome

  1. A 1-year-old girl presents with weight loss and a 2-week history of large, bulky, nonbloody, foul-smelling stools. She has been attending day care and recently received amoxicillin for an ear infection. Which of the following is the most likely cause of her diarrhea?

(A) Entamoeba histolytica

(B) Enterotoxigenic Escherichia coli

(C) Clostridium difficile

(D) Giardia lamblia

(E) Norwalk virus

  1. A 19-year-old boy, a college sophomore, presents with high fever, headache, cough, conjunctivitis, and a diffuse macular rash over his trunk and face. He is unsure of his immunization status. You suspect measles infection. Which of the following is correct regarding this diagnosis?

(A) Vitamin A may improve his outcome.

(B) Koplik spots would likely be present on examination of his mouth.

(C) Mortality is most commonly caused by measles encephalitis.

(D) Diagnosis is based on culture and direct fluorescent antigen testing.

(E) Corticosteroids will decrease symptoms and improve outcome.



The response options for statements 10–14 are the same. You will be required to select one answer for each statement in the set.

For each clinical description, select the most likely cause.

  1. At birth, a term infant is noted to have hydrocephalus and intracranial calcifications on computed tomography of the head. Eye examination reveals bilateral chorioretinitis.

(A) Malaria Plasmodium species

(B) Toxoplasma gondii

(C) Giardia lamblia

(D) Entamoeba histolytica

(E) Coccidioides immitis

(F) Cryptococcus neoformans

(G) Aspergillus fumigatus

(H) Candida albicans

  1. A 5-year-old boy is admitted with a fever of unknown origin. An abdominal computed tomographic scan reveals a large hepatic abscess.

(A) Malaria Plasmodium species

(B) Toxoplasma gondii

(C) Giardia lamblia

(D) Entamoeba histolytica

(E) Coccidioides immitis

(F) Cryptococcus neoformans

(G) Aspergillus fumigatus

(H) Candida albicans

  1. A 12-year-old girl with cystic fibrosis has an exacerbation of her disease and presents with wheezing, pulmonary infiltrates, and eosinophilia.

(A) Malaria Plasmodium species

(B) Toxoplasma gondii

(C) Giardia lamblia

(D) Entamoeba histolytica

(E) Coccidioides immitis

(F) Cryptococcus neoformans

(G) Aspergillus fumigatus

(H) Candida albicans

  1. A 16-year-old boy is admitted to the hospital for a workup of cyclical fevers after a trip to India. His illness began with flulike symptoms.

(A) Malaria Plasmodium species

(B) Toxoplasma gondii

(C) Giardia lamblia

(D) Entamoeba histolytica

(E) Coccidioides immitis

(F) Cryptococcus neoformans

(G) Aspergillus fumigatus

(H) Candida albicans

  1. An 18-month-old girl and three of her day care classmates present with 2 weeks of watery diarrhea and some weight loss.

(A) Malaria Plasmodium species

(B) Toxoplasma gondii

(C) Giardia lamblia

(D) Entamoeba histolytica

(E) Coccidioides immitis

(F) Cryptococcus neoformans

(G) Aspergillus fumigatus

(H) Candida albicans

  1. A 2-year-old boy has a positive tuberculin skin test that measures 12 mm. It was placed during a routine well child care visit. He is well, without fever, chills, cough, weight loss, or night sweats. No known tuberculosis contacts are identified. Which of the following statements regarding this patient's management is correct%

(A) A chest radiograph should be ordered because the tuberculin skin test is positive.

(B) He should be placed into respiratory isolation immediately because he is likely to spread tuberculosis to others.

(C) Isoniazid is not indicated because this tuberculin skin test is negative.

(D) Triple-drug therapy for tuberculosis should be started immediately.

(E) Gastric aspirates should be ordered.



The response options for statements 16–20 are the same. You will be required to select one answer for each statement in the set.

Match the clinical description with the likely causative organism.

  1. While visiting Monterey, Mexico, a 16-year-old boy develops watery, nonbloody diarrhea, without fever.

(A) Salmonella species

(B) Shigella sonnei

(C) Yersinia enterocolitica

(D) Clostridium difficile

(E) Campylobacter jejuni

(F) Vibrio cholerae

(G) Enterotoxigenic Escherichia coli

(H) E. coli 0157:H7

(I) Enteropathogenic E. coli

  1. A 3-year-old boy presents with an acute onset of high fevers, bloody diarrhea, and a generalized tonic-clonic seizure. The stool Wright stain reveals sheets of white blood cells.

(A) Salmonella species

(B) Shigella sonnei

(C) Yersinia enterocolitica

(D) Clostridium difficile

(E) Campylobacter jejuni

(F) Vibrio cholerae

(G) Enterotoxigenic Escherichia coli

(H) E. coli 0157:H7

(I) Enteropathogenic E. coli

  1. An 8-year-old girl presents with a 1-week history of diarrhea and low-grade fever. The family reports that they have recently acquired a pet turtle.

(A) Salmonella species

(B) Shigella sonnei

(C) Yersinia enterocolitica

(D) Clostridium difficile

(E) Campylobacter jejuni

(F) Vibrio cholerae

(G) Enterotoxigenic Escherichia coli

(H) E. coli 0157:H7

(I) Enteropathogenic E. coli

  1. A 10-year-old boy is admitted to the hospital and taken directly to the operating room for suspected acute appendicitis. Surgeons discover a normal appendix but enlarged mesenteric lymph nodes.

(A) Salmonella species

(B) Shigella sonnei

(C) Yersinia enterocolitica

(D) Clostridium difficile

(E) Campylobacter jejuni

(F) Vibrio cholerae

(G) Enterotoxigenic Escherichia coli

(H) E. coli 0157:H7

(I) Enteropathogenic E. coli

  1. A group of travelers to Bangladesh suddenly develop massive, watery, nonbloody diarrhea that results in severe dehydration and electrolyte imbalance.

(A) Salmonella species

(B) Shigella sonnei

(C) Yersinia enterocolitica

(D) Clostridium difficile

(E) Campylobacter jejuni

(F) Vibrio cholerae

(G) Enterotoxigenic Escherichia coli

(H) E. coli 0157:H7

(I) Enteropathogenic E. coli

The response options for statements 21–24 are the same. You will be required to select one answer for each statement in the set.

Match the clinical description with the likely diagnosis.

  1. A 9-month-old girl with mild facial eczema has fever and a facial skin rash. The skin lesion is weepy with a honey-colored crust.

(A) Buccal cellulitis

(B) Impetigo

(C) Necrotizing fasciitis

(D) Erysipelas

(E) Staphylococcal scalded skin syndrome

(F) Toxic shock syndrome

  1. An unvaccinated 4-month-old boy has a facial skin rash and a positive blood culture for Haemophilus influenzaetype b.

(A) Buccal cellulitis

(B) Impetigo

(C) Necrotizing fasciitis

(D) Erysipelas

(E) Staphylococcal scalded skin syndrome

(F) Toxic shock syndrome

  1. An infant boy has fever, an erythematous skin rash, and a positive Nikolsky sign.

(A) Buccal cellulitis

(B) Impetigo

(C) Necrotizing fasciitis

(D) Erysipelas

(E) Staphylococcal scalded skin syndrome

(F) Toxic shock syndrome

  1. A 7-year-old girl develops fever and a rapidly expanding tender skin rash with a well-demarcated border.

(A) Buccal cellulitis

(B) Impetigo

(C) Necrotizing fasciitis

(D) Erysipelas

(E) Staphylococcal scalded skin syndrome

(F) Toxic shock syndrome



Answers and Explanations

  1. The answer is D[II.C.5 and Table 7-1]. Fever in an infant younger than 28 days of age must be taken very seriously because the neonate's immune system is immature. As a result, the current appropriate management for any neonate with fever (temperature >100.4° F [>38° C]) includes a complete workup for serious bacterial infection that includes evaluation of blood, urine, and cerebrospinal fluid for evidence of bacterial infection; administration of empiric intravenous antibiotics; and hospitalization. The risk of serious bacterial infection in a nontoxic infant younger than 3 months of age is approximately 3–10%. Usual bacteria resulting in infection in this age group include group B streptococcus, Escherichia coli, and Listeria monocytogenes.
  2. The answer is B[II.D.3 and Table 7-1]. Because of the patient's elevated fever, evaluation for bacteremia and urinary tract infection, including urine culture, urinalysis, complete blood count, and blood culture, is indicated. After these laboratory studies, intramuscular ceftriaxone may be given either empirically or only if the white blood count is ≥ 15, 000 cells/mm3. Hospitalization is generally not required unless the patient is toxic in appearance, dehydrated, or has poor ability to return to the physician for follow-up. Neither evaluation of spinal fluid nor a chest radiograph is indicated in this nontoxic patient without respiratory signs or symptoms. Neither intravenous antibiotics nor hospitalization is indicated because the infant is nontoxic and well hydrated.
  3. The answer is D[XIII.B]. This patient's clinical presentation with fever, lymphadenopathy, pharyngitis, and splenomegaly is most consistent with infectious mononucleosis. If a child with infectious mononucleosis is mistakenly given amoxicillin, a diffuse pruritic rash may develop. Monospot testing is highly sensitive in older children, but heterophile antibodies do not reliably form in children younger than 4 years of age. Antibody titers are therefore the preferred diagnostic test in such young children. The most common cause of infectious mononucleosis is Epstein-Barr virus. Although supportive care for infectious mononucleosis is appropriate, symptoms of infection may last weeks, and contact sports restriction is advised because of the risk of splenic rupture. Splenomegaly is not consistent with the diagnosis of streptococcal pharyngitis.
  4. The answer is C[IV.C.3 and Table 7-3, 7-4]. This cerebrospinal fluid (CSF) evaluation is most consistent with aseptic meningitis, specifically viral meningitis. Enteroviruses are the most common cause of viral meningitis and most often occur during the summer and fall. Early in viral meningitis, the white blood count (WBC) in the CSF may demonstrate a polymorphonuclear cell predominance that shifts to a lymphocyte predominance within 24–48 hours. The normal protein and glucose and negative Gram stain are also consistent with viral meningitis. Meningitis caused by Neisseria meningitidisor Streptococcus pneumoniae would be reflected by a higher CSF WBC, lower glucose, and higher protein. Although patients with Lyme meningitis, which is caused by Borrelia burgdorferi, may present with an aseptic CSF profile, the onset is not as acute as in this patient. Patients withMycobacterium tuberculosis present with a low to very low glucose and elevated protein level in the CSF.
  5. The answer is A[IV.B.5]. Empiric therapy of presumed bacterial meningitis should include a third-generation cephalosporin and the addition of vancomycin until sensitivities are available, because of the high level of pneumococcal antibiotic resistance in many communities. Ampicillin is not indicated; this child is out of the age range at which Listeriainfection occurs. Acyclovir is not indicated; the cerebrospinal fluid profile is most consistent with bacterial meningitis. Corticosteroids are effective in reducing the incidence of hearing loss in Haemophilus influenzaetype b meningitis but have not been shown to be effective for other bacterial pathogens.
  6. The answer is C[XIII.A.2]. Factors that increase the risk of HIV transmission from mother to infant include high maternal viral load (measured by RNA copy number) at delivery, concomitant chorioamnionitis or other genital tract infections, primary or advanced maternal HIV infection, premature birth, and prolonged rupture of membranes. Transmission may also occur through breast milk. Transmission is decreased through the use of maternal antiretroviral therapy, newborn prophylaxis with antiretroviral agents (e.g., zidovudine), birth by cesarean section, and low maternal viral load.



  1. The answer is B[IX.A.5.f]. This patient's clinical presentation of a sandpaper-like rash associated with pharyngitis and fever is consistent with scarlet fever, caused by erythrogenic toxin-producing strains of group A β-hemolytic streptococcus (GABHS). Although there are multiple complications of GABHS infection, including rheumatic fever, glomerulonephritis, reactive arthritis, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS), only PANDAS and rheumatic fever will be prevented by treatment with antibiotics.
  2. The answer is D[Table 7-6, 7-7, XV.B.3]. Infection with the protozoan Giardia lambliais associated with bulky, foul-smelling stools, weight loss, and day care attendance.Entamoeba histolytica and Clostridium difficile generally cause bloody diarrhea. Escherichia coli infection generally results in short-term watery diarrhea. Day care attendance is also associated with Norwalk virus; however, symptoms of Norwalk virus infection generally last only 48–72 hours.
  3. The answer is A[XIII.C.3, XIII.C.4, XIII.C.5]. This patient's presentation is most consistent with measles infection. Management includes supportive care, and vitamin A therapy may also be beneficial. Koplik spots are transient, and by the time the rash is present, Koplik spots are no longer appreciated. Bacterial pneumonia is the most common complication of measles infection and is the most common cause of mortality. Diagnosis is based on confirmation by serologic testing in the presence of typical clinical features. Corticosteroids do not play a role in the therapy of measles.

10–14. The answers are B, D, G, A, and C, respectively [XV.D.3, XV.A.3, XIV.A.2, XV.C.3, and XV.B.3]. The triad of intracranial calcification, hydrocephalus, and chorioretinitis is consistent with congenital toxoplasmosis, which is caused by Toxoplasma gondii. Entamoeba histolytica may result in asymptomatic infection or colitis. The most common extraintestinal complication is a liver abscess. Aspergillus infection may result in invasive disease or in noninvasive allergic disease characterized by wheezing, eosinophilia, and pulmonary infiltrates. Malaria classically presents with a flulike illness followed by the development of high fevers that cycle in 48- to 72-hour paroxysms. Giardia lamblia typically presents with bulky, large-volume, watery stools that eventually lead to weight loss.

  1. The answer is A[XVII.C]. A tuberculin skin test is considered positive depending on a patient's specific risk factor(s) for acquisition of tuberculosis. A tuberculin skin test ≥ 10 mm is considered positive if the patient is younger than 4 years of age or if the patient resides or has lived in an area endemic for tuberculosis. Therefore, given that the tuberculin skin test is positive, a chest radiograph to evaluate for pulmonary tuberculosis is indicated. Children younger than 12 years of age with tuberculosis are unlikely to be contagious because of minimal cough and pulmonary involvement. Medications for tuberculosis disease (e.g., triple-drug regimen) are indicated if the patient has signs and symptoms of tuberculosis. Gastric aspirates are indicated only if the chest radiograph reveals pulmonary disease.

16–20. The answers are G, B, A, C, and F, respectively [Table 7-6]. Enterotoxigenic Escherichia coli is the major cause of traveler's diarrhea and results in nonbloody watery stools. Bloody stools may result from infection with Salmonella, Shigella, Yersinia, Campylobacter, enterohemorrhagic E. coli, and Clostridium difficile. Shigella may be associated with seizures caused by the release of a neurotoxin. Salmonella may be acquired by ingestion of contaminated poultry or by exposure to turtles and lizards that carry the organism.Yersinia may result in mesenteric adenitis that causes pain mimicking acute appendicitis. Infection with Vibrio cholerae generally occurs in developing countries and causes massive fluid loss from the gut.

21–24. The answers are B, A, E, and D, respectively [IX.A]. Buccal cellulitis is characterized by a bluish color to the cheeks of a young child; this condition is typically caused by infection with Haemophilus influenzae type b, which is identified on blood culture. Impetigo typically presents with honey-crusted lesions on the face; it is caused by infection withStaphylococcus aureus and group A β-hemolytic streptococcus. Staphylococcal scalded skin syndrome is manifested by Nikolsky sign, or the extension of bullae with lateral pressure applied to the skin. Fever, tender skin, and widespread bullae are present. Erysipelas is characterized by tender, erythematous skin, but the border is well demarcated.

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