Current Diagnosis & Treatment in Infectious Diseases

Section V - Bacterial Infections

67. Chlamydia

Jose G. Montoya MD

General Considerations

Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae are among the most prevalent microbial pathogens in humans worldwide. C trachomatis is responsible for a variety of sexually transmitted disease (STD) syndromes in both sexes. In addition, certain serotypes of C trachomatis are responsible for trachoma, the most common infectious cause of blindness in humans. C psittaci is a zoonotic pathogen associated with atypical pneumonia. C pneumoniae infects approximately one-half of the world's human population and is a cause of upper and lower respiratory tract disease. It has also been associated with atherosclerotic cardiovascular disease.

  1. Epidemiology.In the United States, genital infections by C trachomatisserovars D through K occur frequently among sexually active adolescents and young adults. These serovars are also important perinatal pathogens. In 1998, > 600,000 cases were reported in the United States (237 per 100,000 population), making it the most common notifiable infectious disease in this country. Asymptomatic infection is rather common in both women and men. Prevalence rates vary according to the geographic locale and the specific populations. The prevalence of urethral infection among young men is < 10% for those seen in general medical settings, between 10% and 15% for asymptomatic soldiers undergoing routine medical care, and > 10% for heterosexual men seen in STD clinics. The prevalence of C trachomatis genital infection among women is 5% for asymptomatic college students, > 10% for women monitored in family-planning clinics, and > 20% for women seen in STD clinics. Chlamydial genital infections are found at a higher rate among women who use oral contraceptives or have cervical ectopy. It is estimated that 5–25% of pregnant women in the United States carry C trachomatis in their cervix. Of the neonates who get infected during birth, ~ 25% develop inclusion conjunctivitis, and 10% develop pneumonia.

Lymphogranuloma venereum (caused by serovars L1, L2, and L3) is a rare disease in the United States. The vast majority of cases are transmitted sexually, but transmission by nonsexual routes has been documented.

C trachomatis serovars A, B, Ba, and C cause trachoma, one the most common causes of preventable blindness in the world. These serovars are usually transmitted from person to person (most often involving a child) via hands and fomites. Endemic areas include Asia, the Middle East, sub-Saharan Africa, and northern Africa.

C psittaci is usually transmitted to humans by contact with birds or from occupational exposure in avian-processing plants or poultry farms. Essentially all common birds and several wild species are capable of carrying the organism and shedding it while remaining healthy. Only brief exposure to an area where an infected bird has been present is necessary for transmission of C psittaci. Rarely, the bite of a bird transmits the disease.

C pneumoniae was established as a human respiratory pathogen in 1983, and it is now associated with 6–12% of cases of community-acquired pneumonia. Approximately 50% of persons worldwide have been infected by early adulthood. Outbreaks of C pneumoniae respiratory disease have been described especially in military recruits but also in the general population; the highest rates of C pneumoniae pneumonia are found among the elderly. There is no seasonal predominance. Exchange of respiratory secretions by aerosol route or by hand appears to be the primary mode of transmission of C pneumoniae. In more recent years, this organism has been associated with atherosclerosis and coronary artery disease.

  1. Microbiology.Members of the genus Chlamydiaare small, obligate intracellular prokaryotic organisms. They contain DNA, RNA, ribosomes, and a discrete cell envelope. The envelope lacks peptidoglycan between the inner and outer membranes, which explains why cell wall-active antibiotics have no role in the treatment of chlamydial infections. During their unique life cycle, Chlamydia species are observed in two distinct forms: the extracellular elementary body and the intracellular reticulate body. The elementary body is responsible for person-to-person transmission. It attaches to, and is engulfed by mammalian target cells. Within the phagosome, the elementary bodies reorganize and develop into reticulate bodies, which are adapted for intracellular survival and multiplication. After multiple rounds of replication by binary fission, the reticulate bodies condense and form elementary bodies. The elementary bodies eventually rupture the host cell to continue the cycle by infecting other contiguous cells. The complete genome sequences of C trachomatis and C pneumoniae reveal a large number of genes that are most similar to versions found in eukaryotes, emphasizing the coevolution of pathogen and host. Despite their distant relationship with the gram-negative bacilli, both Chlamydia species contain genes that appear to encode a “type III” secretion system typically associated with invasiveness and other virulence attributes.

Members of the genus Chlamydia share a common heat-stable lipopolysaccharide antigen and specific cell envelope protein antigens which facilitate their classification into a number of serotypes. Protein antigenic and gene sequence variability of the major outer-membrane protein have led to the identification of at least 20 sero- and sequence types of C trachomatis. The vast majority of the serotypes can be assigned to one of three major groups: (1) serovar group A, B, Ba, and C, which is associated with trachoma; (2) serovar group D, E, F, G, H, I, J, and K, which is associated with sexually transmitted and perinatally acquired infections; and (3) serovar group L1, L2, and L3, which is associated with lymphogranuloma venereum and hemorrhagic proctocolitis.

  1. Pathogenesis.Chlamydiaspecies rupture mammalian cells after unregulated replication of elementary bodies; pathology results from this cell lysis, as well as damage caused by recruited inflammatory cells and cytokine mediators. Repeated or persistent exposure is believed to elicit more intense host inflammatory responses, some of which may be directed at chlamydial heat shock proteins. A crucial and common pathologic endpoint of chlamydial infection is scarring of mucous membranes, especially of the conjunctiva (trachoma) and female upper genital tract (resulting in infertility).

The elementary body of C trachomatis attaches to host epithelial cells by using heparan sulfate as a bridging ligand and later infects mononuclear leukocytes in lymph nodes via the local lymphatic draining system. Immunity against C trachomatis appears to protect only partially against reinfection.

C psittaci is acquired through inhalation of respiratory secretions or aerosolized droppings of infected birds; it spreads via the bloodstream and eventually reaches reticuloendothelial cells of the spleen and liver. Pneumonitis is characterized by edema, necrosis, erythrocytes, and a chronic inflammatory cellular infiltrate.

Little is known regarding the pathogenesis of C pneumoniae. It appears that C pneumoniae has a less rigid cell wall than that in other chlamydial species.

Diagnosis

Chlamydial infections require laboratory studies for a definitive diagnosis. Available laboratory techniques include cytology, culture, serology, and demonstration of chlamydial antigens or nucleic acid sequences.

Treatment

Antimicrobial agents such as the tetracyclines, certain macrolides, and some fluoroquinolones are highly active against Chlamydia infections. Clinically relevant resistance to these antibiotics has not been observed. All sex partners of patients with sexually transmitted chlamydial infections should be referred for evaluation and treatment.

C TRACHOMATIS INFECTIONS

Essentials of Diagnosis

  • Typical intracytoplasmic inclusions in Giemsa-stained cell scrapings from the conjunctiva.
  • Ligase chain reaction (LCR) or polymerase chain reaction (PCR) in first-void urine.
  • Positive culture in McCoy or HeLa cells of body fluids or secretions.
  • Positive microimmunofluorescence serology for suspected cases of lymphogranuloma venereum and infants with pneumonia.
  • Complement fixation titer of 1:64 or greater in patients with presumed lymphogranuloma venereum.

Clinical Syndromes

C trachomatis is associated with urethritis, proctitis, conjunctivitis, and arthritis in women and men; epididymitis in men; and mucopurulent cervicitis (MPC), acute salpingitis, bartholinitis, and the Fitz-Hugh and Curtis syndrome in women (Box 67-1). C trachomatis and Neisseria gonorrhoeae (see Chapter 52) coinfections are common in women with MPC and men with urethritis. In men, C trachomatis is the most common etiologic agent of the nongonococcal (NGU) and postgonococcal urethritis (PGU) syndromes. In college-age women, in the absence of infection with Escherichia coli or Staphylococcus saprophyticus, C trachomatis is the most common etiologic agent of urethritis.

  1. Urethritis.Urethritis is characterized in women by the presence of dysuria and frequency without urgency or hematuria and in men by discharge, frequency, and dysuria. Urethritis should be documented by the presence of mucopurulent or purulent discharge, by a Gram stain of urethral secretions demonstrating ≥ 5 leukocytes per oil immersion field, or by demonstrating a positive leukocyte esterase test or ≥ 10 leukocytes per high-power field on first-void urine. NGU is diagnosed in men with urethritis in whom gram-negative intracellular diplococci (N gonorrhoeae) cannot be detected in a gram-stained urethral discharge or swab specimen. PGU is diagnosed in men with persistent urethritis 2–3 weeks after treatment of gonococcal urethritis with beta-lactam antibiotics, which are ineffective against C trachomatis.Although the discharge from chlamydial urethritis is more watery, less purulent, and less abundant than the discharge from gonococcal urethritis, attempts to distinguish between the two on clinical grounds alone can be problematic. Physical examination in cases of chlamydial urethritis can be entirely normal or reveal meatal erythema and tenderness, urethral discharge, or both. It should be emphasized that asymptomatic C trachomatis infections can lead to long-term sequelae in the genitourinary tract.
  1. Mucopurulent Cervicitis.MPC is defined by the presence of mucopurulent or purulent endocervical discharge in the endocervical canal or in an endocervical swab specimen. It has been suggested that the diagnosis can also be made on the basis of easily induced cervical bleeding. The most common complaints are vaginal discharge, vaginal bleeding, abdominal pain, and dysuria, although most infected women are asymptomatic. Physical examination reveals cervical edema, ectopy, and a propensity of the endocervical mucosa to bleed when rubbed with a swab.
  2. Proctitis.Proctitis can be caused by C trachomatisserovars D through K and serovars L1, L2, and L3. It occurs primarily in men who have sex with men and practice receptive anorectal intercourse. It can occur also in heterosexual women. Patients usually present with rectal pain, tenesmus, and rectal exudate; hematochezia may be present. Gram stain of the rectal discharge reveals neutrophils. Anoscopic examination reveals mucopurulent discharge with a patchy mucosal friability of the distal third segment of the rectum. The L1, L2, and L3 strains rarely cause disease in the United States and produce a more severe syndrome of ulcerative proctitis or even proctocolitis; this presentation can be confused with herpes simplex virus (HSV) proctitis or Crohn's disease. Proctocolitis can lead to perianal fistulas and rectal strictures.
  3. Lymphogranuloma Venereum.C trachomatisserovars L1, L2, and L3 are also responsible for the syndrome of lymphogranuloma venereum (LGV). The most frequent manifestation of LGV among heterosexual men is tender unilateral inguinal or femoral lymphadenopathy or both. The lymphadenopathy becomes associated with perinodal inflammation and formation of a bubo. Men who have sex with men and women may present with the proctocolitis syndrome (see above). Most patients present at the time of lymphadenopathy and no longer have the primary painless self-limited nodular or ulcerative lesion at the inoculation site.
  4. Epididymitis.Epididymitis should be suspected in patients with unilateral testicular pain, with or without fever, and unilateral epididymal tenderness or swelling on physical examination. In men younger than 35 years, C trachomatisis by far the most common etiologic agent, followed by N gonorrhoeae. In men older than 35, E coli and Pseudomonas aeruginosa are the most common etiologic agents; these infections usually occur in the setting of urologic manipulation. In each case of suspected epididymitis, torsion of the ipsilateral testicle should be ruled out. Clinically available tests to rule out testicular torsion include Doppler ultrasound and nuclear medicine studies. In patients in whom the clinical suspicion for testicular torsion is high (eg, a young person who presents with acute unilateral testicular pain without urethritis), surgical exploration may be indicated. In patients with chronic unilateral testicular pain who do not respond to appropriate antibacterial therapy, other etiologies such as carcinoma or tuberculosis should be considered.
  5. Pelvic Inflammatory Disease.Pelvic inflammatory disease (PID) comprises a spectrum of inflammatory disorders of the female upper genital tract, including any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. C trachomatisand N gonorrhoeae are the two most common etiologic agents. Other organisms such as anaerobes, Streptococcus agalactiae, Gardnerella vaginalis, enteric gram-negative bacilli, Ureaplasma urealyticum, and Mycoplasma hominis have also been implicated as etiologic agents of PID. PID can present with subtle or mild symptoms and may also be asymptomatic. Initially, symptoms may not necessarily indicate involvement of the genital tract. PID should be suspected in sexually active women who present with lower abdominal pain or tenderness, adnexal tenderness, and/or cervical motion tenderness and in whom no other cause for these symptoms can be identified. Other causes of abdominal pain in this setting include ectopic pregnancy and acute appendicitis. In addition, PID can present with fever (>101°F), abnormal vaginal or cervical discharge, vaginal bleeding, dyspareunia, or some combination of these symptoms. Erythrocyte sedimentation rate or C-reactive protein may be elevated.
  1. Reiter's Syndrome.Reiter's syndrome consists of conjunctivitis or uveitis, urethritis, arthritis, and mucocutaneous lesions that usually occur in human leukocyte antigen (HLA)-B27-positive individuals ~ 1–6 weeks after acquisition of a sexually transmitted or dysenteric agent. The first three features constitute the classic triad. Reiter's syndrome can present with all of the features mentioned above or in any combination of those symptoms. NGU may in fact be the first sign of this syndrome. In women, cervicitis can be part of the syndrome. The knees are the most commonly affected joints. Reiter's has been described after infection with enteric pathogens such as Salmonella, Shigella, or Campylobacterspecies, as well as C trachomatis genital-tract infection.
  2. Perinatal Infections.Perinatal infections with C trachomatisresult from exposure of the neonate to the organism present in the mother's cervix. Initial infection results in colonization of the mucous membranes of the eye, oropharynx, urogenital tract, and rectum. Infection of the newborn with C trachomatis is first manifested by the presence of conjunctivitis, which usually develops between 5 and 14 days after birth. Other infectious agents capable of causing conjunctivitis in neonates include N gonorrhoeae, Haemophilus influenzae, S pneumoniae, and HSV. Typically, N gonorrhoeae has an incubation period of only 1–3 days. However, laboratory tests are required for a microbiologic diagnosis. Pneumonia can develop in neonates as a subacute, afebrile respiratory syndrome with onset at between 1 and 3 months of age. Infants usually develop cough, tachypnea, and bilateral diffuse interstitial infiltrates. Neonatal infections of the oropharynx, genital tract, and rectum are usually asymptomatic.
  3. Eye Infections.C trachomatis causes eye disease in children and adults, and this disease takes two distinct clinical and epidemiological forms: trachoma and adult inclusion conjunctivitis. Trachoma is a chronic inflammatory condition of the ocular and palpebral conjunctiva and cornea caused by C trachomatis serovars A, B, Ba, and C. It occurs in the setting of poor hygiene and crowded conditions. A follicular conjunctivitis is usually followed by superficial neovascularization of the cornea (pannus formation). Subsequent scarring of the conjunctiva and cornea eventually leads to blindness. Adult inclusion conjunctivitis results from sexual transmission of C trachomatis serovars D through K. It usually presents as an acute unilateral follicular conjunctivitis and periauricular lymphadenopathy; this presentation is clinically similar to that of adenovirus or HSV conjunctivitis. If left untreated, it can evolve into a syndrome of chronic conjunctivitis but rarely results in conjunctival or corneal scarring.

BOX 67-1 C trachomatis Infections

 

Women

Men

Children

More Common

· Mucopurulent cervicitis

· Acute salpingitis1

· Endometritis1

· Bartholinitis

· Acute urethral syndrome

· Nongonococcal urethritis

· Postgonococcal urethritis

· Epididymitis

· Inclusion conjunctivitis in infants

· Pneumonia in infants

Less Common

· Perihepatitis

· Proctitis

· Conjunctivitis

· Reiter's syndrome

· Proctitis

· Conjunctivitis

· Reiter's syndrome

· Otitis media

· C trachomatis in genital secretions should raise the suspicion of sexual abuse

1These syndromes are also categorized under the syndrome PID.

Diagnosis

  1. Urethritis.In men with suspected nongonococcal or postgonococcal urethritis, the diagnosis of urethritis should be confirmed based on the results of urinalysis with ≥ 10 leukocytes per high-power field or on Gram stain examination of the urethral discharge revealing > 4 neutrophils per oil immersion field. The absence of N gonorrhoeaeshould be documented with a properly performed Gram stain examination of the urethral material. Nucleic acid amplification methods for use with either urine or urethral/cervical swab specimens are the most sensitive and specific tests for the definitive diagnosis of C trachomatis genital-tract infection. The two most commonly used amplification methods are LCR and PCR. Since these methods can be used with first-void urine, an uncomfortable swab procedure is not necessary, thereby facilitating widespread diagnostic testing and screening of populations at risk.
  2. Epididymitis, Proctitis, and Mucopurulent Cervicitis.In young men with epididymitis, urethritis needs to be ruled out (see preceding section). In a similar fashion, N gonorrhoeaeshould be excluded in patients who have both testicular pain and urethral discharge. Amplification of C trachomatis DNA from urine based on PCR or LCR is the diagnostic approach of choice. This sensitive and specific approach has also replaced cervical-swab specimen culture for assessing the possibility of C trachomatis cervicitis. For the diagnostic workup of proctitis, a rectal culture or direct immunofluorescence test for C trachomatis is indicated.
  3. PID.The diagnosis of PID is difficult. Symptoms, signs, and laboratory tests are not specific. Women with symptomatic PID can present with any combination of the following: pelvic pain including adnexal and/or cervical-motion tenderness, palpable adnexal mass, and/or elevated erythrocyte sedimentation rate, C-reactive protein, or peripheral leukocyte count.
  4. Reiter's Syndrome.In those with clinical features of Reiter's syndrome, evidence of C trachomatisshould be sought. A stool examination should also be performed for the gastrointestinal-tract pathogens associated with Reiter's syndrome, and the possibility of the HLA-B27 haplotype should be assessed.
  1. Lymphogranuloma Venereum.The diagnosis of LGV is confirmed by isolation of an LGV serovar from the lymph node or rectum and occasionally from the urethra or cervix. An LGV complement fixation titer of ≥ 1:64 or a microimmunofluorescence titer of ≥ 1:512 is considered diagnostic.
  2. Perinatal Infections.Purulent conjunctival discharge in a neonate should be evaluated with Gram stain and bacterial cultures to rule out N gonorrhoeae, Haemophilusspp., S pneumoniae, and Staphylococcus aureus. C trachomatis antigen can be detected directly, and the organism can be cultivated from conjunctival discharge. A Giemsa-stained scraping of the conjunctiva is less sensitive for detecting Chlamydia cells but is the most rapid method for diagnosis. Chlamydial culture of sputum, pharynx, eye, and rectum should be obtained in infants with pneumonia. Serological tests may help if a fourfold change is observed in immunoglobulin (Ig) G or IgM titers, but a single IgG measurement may be misleading because of passive transfer of maternal antibody. The two samples should be obtained ≥ 4 weeks apart and analyzed in parallel.
  3. Eye Infections.Trachoma can be diagnosed on clinical grounds and in the proper epidemiological setting. Confirmation of the diagnosis can be achieved by Giemsa-stained cell scrapings from the conjunctiva and detection of typical intracytoplasmic inclusions.

Treatment

  1. Urethritis.Adults with NGU or PGU should be treated as soon as possible after diagnosis. A single-dose regimen based on azithromycin for example has the important advantage of improved adherence (Box 67-2). Doxycycline, erythromycin, or ofloxacin can also be used. Ofloxacin is also often effective against N gonorrhoeae.Other drugs used against N gonorrhoeae such as the cephalosporins and ciprofloxacin are not effective against C trachomatis.Patients with recurrent or persistent urethritis should be evaluated for the possibility of nonadherence, reinfection, or an alternative diagnosis. In this setting, patients should be re-treated if they do not comply fully or have been re-exposed to an untreated sex partner. A combination regimen consisting of metronidazole plus erythromycin has been suggested for patients with a history of recurrent urethritis, who have adhered to the initial regimen and have not been re-exposed. In the absence of reliable negative data for N gonorrhoeae, empiric antibiotic coverage for this organism should be provided as well.
  2. Mucopurulent Cervicitis, Proctitis, Epididymitis, and PID.Patients with mucopurulent cervicitis, proctitis, and epididymitis should be tested for C trachomatisand N gonorrhoeae, as above, and treated with drugs effective against both (Box 67-2). PID is managed similarly, except that antimicrobial coverage against anaerobes is often included. In addition, treatment is often begun via an intravenous route. Erythromycin is the drug of choice for pregnant women with C trachomatis infection; amoxicillin has also been successful in this setting. Single-dose azithromycin is another alternative during pregnancy. Tetracyclines and fluoroquinolones are contraindicated in pregnant women.
  3. Lymphogranuloma Venereum.LGV is treated with doxycycline (Box 67-3). Alternative drugs include macrolides such as erythromycin. The activity of azithromycin against C trachomatissuggests that it may be effective in treating LGV given in multiple doses over 2–3 weeks, but clinical data regarding its use for this disease are lacking.

Patients with suspected or proven C trachomatis infection should be instructed to refer their sex partners (sexual contacts during the 60 days preceding onset of symptoms or diagnosis of chlamydial infection) for diagnostic testing, treatment, or both. However, the last sexual contact should be treated even if the time of the last sexual contact was > 60 days before onset of symptoms or diagnosis. Patients and their sex partners should abstain from sexual activity until treatment courses are completed.

Unless symptoms persist or reinfection is suspected, patients treated with doxycycline or azithromycin do not need to be retested for chlamydial infection because these drugs are highly effective. A test of cure may be considered 3 weeks after completion of a course of erythromycin.

  1. Perinatal Infection.Erythromycin is the drug of choice for infants with C trachomatisocular infection, as well as with C trachomatis pneumonia (Box 67-4). Mothers of infants with chlamydial infection and the sex partners of these women should be assessed and treated for C trachomatis infection. Newborns of mothers who have untreated chlamydial infections should be monitored closely for symptoms of conjunctivitis or pneumonia. Prophylactic antibiotics are not indicated in this setting.
  2. Infections in Young Children.Chlamydial infections in preadolescent children should raise the possibility of sexual abuse. Because of the potential for a criminal investigation, the diagnosis of C trachomatisin this situation requires isolation in cell culture.

In children who weigh < 45 kg, erythromycin is the drug of choice. In children who weigh ≥ 45 kg but who are < 8 years of age, azithromycin is the drug of choice. In children, ≥ 8 years of age, doxycycline can be used as an alternative to azithromycin. (See Box 67-2.)

  1. Eye Infections.Patients with trachoma conjunctivitis respond well to a tetracycline, azithromycin, or erythromycin (Box 67-4). Public health programs for management of endemic trachoma consist of mass application of tetracycline or erythromycin ophthalmic ointment to all children in affected communities for 21–60 days or on an intermittent basis. Surgical correction of eyelids is also undertaken.

Adult inclusion conjunctivitis is usually treated with an oral tetracycline or erythromycin. All sexual contacts should be evaluated, treated for C trachomatis infection, or both.

BOX 67-2 Treatment of C trachomatis Genital Infections (Serovars D–K)1,2

First Choice

· Azithromycin, 1 g orally in a single dose
OR

· Doxycycline, 100 mg orally twice a day for 7 d

Second Choice

· Erythromycin base, 500 mg orally four times a day for 7 d
OR

· Erythromycin ethylsuccinate, 800 mg orally three times a day for 7 d
OR

· Ofloxacin, 300 mg orally twice a day for 7 d

Pediatric Considerations3

· Erythromycin, 40 mg/kg/d orally, divided into 4 doses/day, for 14 days
OR

· Doxycycline (children ≥ 8 years old), 4 mg/kg/d orally in 2 divided doses for 14 days

1Sex partners should be evaluated, tested, and treated if they had sexual contact with the patient during the 60 days preceding onset of symptoms. The most recent partner should be treated even if time of the last sexual contact was > 60 days preceding onset of symptoms.

2Coinfection with C trachomatis often occurs among patients who have gonococcal infection.
3Children with genital C trachomatis infection should raise the possibility of sexual abuse.

BOX 67-3 Treatment of Lymphogranuloma Venereum (Serovars L1, L2, and L3)1

First Choice

· Doxycycline, 100 mg orally twice a day for 21 days

Second Choice

· Erythromycin base, 500 mg orally four times a day for 21 days

1 Sex partners should be evaluated, tested, and treated if they had sexual contact with the patient during the 30 days preceding onset of symptoms

BOX 67-4 Treatment of Other C trachomatis Infections

Infant Pneumonia and Ocular Infections

· Erythromycin, 50 mg/kg/d in four divided doses for 10–14 d

Adult Inclusion Conjunctivitis1

· Doxycycline, 100 mg orally twice a day for 1–3 weeks
OR

· Erythromycin, 250 mg four times a day orally for 1–3 weeks

1Topical treatment is not recommended.

Prevention

Programs aimed at the detection of asymptomatic chlamydial infection and treatment of both symptomatic and asymptomatic cases have proven to be effective in decreasing the prevalence of Chlamydia infections in the United States. In addition, behavioral interventions designed for primary prevention of STDs are of paramount importance. A sexual history should be obtained from all patients who are sexually active as a first step in identifying patients at risk and in delivering prevention messages. A professional, compassionate, and nonjudgmental attitude is essential. The most effective strategy for prevention of STDs is avoidance of infected sex partners; however, this is difficult given the prevalence of asymptomatic infection. Information should be provided regarding abstinence especially to those who are being treated for an STD or whose partners are undergoing treatment. The direct relationship between the number of sex partners and the likelihood of STDs must be discussed. A vaccine against chlamydial disease has not yet been developed. Institution of basic hygienic practices such as hand washing is beneficial in reducing the prevalence of trachoma. In addition, mass treatment with azithromycin appears to result in markedly decreased levels of disease.

C PSITTACI INFECTIONS

Essentials of Diagnosis

  • History of contact with birds.
  • Positive C psittaci-specific microimmunofluorescence serologies.
  • Positive complement fixation titers (not species specific).

 

Clinical Findings

  1. Signs and Symptoms.Pneumonia, pericarditis, myocarditis, and endocarditis have been attributed to C psittaciinfection (psittacosis or ornithosis) (Box 67-5). The incubation period for the pneumonia is usually 1–2 weeks. Its onset is gradual with body temperature increasing over a period of 5–7 days; however, there are cases in which the onset is sudden with rigors and temperatures as high as 104°F. Headache is a salient and important symptom; it can be severe and incapacitating. Cough is usually nonproductive and hacking; however, on occasion a mucoid sputum or hemoptysis may develop. Epistaxis, photophobia, myalgias, and back and neck muscle stiffness are also common accompanying symptoms. Pleurisy, friction rub, and pleural effusion are rare, as are mental status changes, which can eventually progress to coma. Other unusual manifestations include gastrointestinal symptoms, such as abdominal pain, nausea, vomiting, or diarrhea.

On physical exam, the pulse rate may be slow relative to the degree of fever (pulse-temperature dissociation). However, this relative bradycardia may be influenced by the physical conditioning and resting heart rate of the individual. Lung auscultation may be entirely normal even in patients who are severely ill or have extensive radiological changes. Splenomegaly has been described in ≤ 70% of patients with C psittaci pneumonia. Abdominal distension, constipation, or pulmonary infarction can occur as late complications.

  1. Laboratory Findings.The peripheral leukocyte count and erythrocyte sedimentation rate are usually normal or can be only slightly elevated.
  2. Imaging.Chest radiographic changes are protean and nonspecific. Radiological abnormalities include infiltrates, which can be patchy, diffuse, lobar, atelectatic, wedge shaped, nodular, or miliary.

Diagnosis

The diagnosis of psittacosis can be confirmed by isolation of C psittaci or by serological tests. However, owing to its fastidious growth requirements and the associated hazards of its growth to laboratory personnel, most clinical laboratories do not attempt cultivation of this organism. Serological testing is best performed using acute and convalescent serum samples.

BOX 67-5 C psittaci Infections in Adults and Children

More Common

· Community-acquired pneumonia with nonproductive cough, fever, and headache (exposure to birds)

Less Common

· Mononucleosis-like syndrome with pharyngitis, hepatosplenomegaly, and lymphadenopathy

· Typhoidal form with fever, bradycardia, malaise, and splenomegaly

· Endocarditis, myocarditis, and pericarditis

Treatment

Patients with C psittaci infection should be treated with a tetracycline (Box 67-6). Patients usually respond with amelioration of their symptoms within 24–48 h after institution of therapy. In patients allergic to or intolerant of tetracyclines, erythromycin can be used as an alternative.

The recommended treatment of psittacosis in children ≥ 8 years of age is 500 mg of tetracycline every 6 h, orally, for 7–10 days. Erythromycin also can be used (50 mg/kg/d up to 2 g/d for 7–10 days). Tetracycline may be more effective than erythromycin.

Prevention

Imported birds should be quarantined and treated with a tetracycline for 30 days. An additional course of tetracycline for 15 days should be given by the importers or owners. Some birds will still shed the organism if treatment courses of < 45 days are used.

C PNEUMONIAE INFECTIONS

Essentials of Diagnosis

  • Hoarseness may accompany atypical pneumonia.
  • Positive C pneumoniae-specific microimmunofluorescence serologies.
  • Positive complement fixation titers (not species specific).
  • Isolation and PCR techniques available in research laboratories only.

BOX 67-6 Treatment of C psittaci Infections

First Choice

· Tetracycline, 500 mg four times a day for 10–21 days
OR

· Doxycycline 100 mg orally twice a day for 10–21 days

Second Choice

· Erythromycin base, 500 mg orally four times a day for 7 d (erythromycin may be less efficacious in severe cases)

Pediatric Considerations

· Erythromycin, 50 mg/kg/d orally up to 2 g/d for 7–10 days
OR

· Tetracycline (children ≥ 8 years old), 500 mg every 6 h for 7–10 days

BOX 67-7 C pneumoniae Infections in Adults and Children

More Common

· Community-acquired pneumonia

· Possible association with atherosclerotic cardiovascular disease

· Possible association with adult-onset asthma and acute exacerbations among adults with asthma

Less Common

· Bronchitis

· Pharyngitis

· Sinusitis

· Endocarditis

· Lumbosacral meningoradiculitis

· Erythema nodosum

· Encephalitis

Clinical Findings

Upper- and lower-respiratory-tract infections including sinusitis, pharyngitis, bronchitis, and pneumonia have been associated with C pneumoniae infection (Box 67-7). Bronchitis and pneumonia are the most common syndromes seen in clinical practice. The incubation period for C pneumoniae pneumonia has been estimated at ~ 21 days. Patients usually present with a history of fever and prominent upper respiratory symptoms followed by sore throat and nonproductive cough. Physical exam can be entirely normal or can reveal mild to moderate respiratory distress, usually with minimal auscultatory changes. The leukocyte count is usually normal or slightly elevated. Chest radiography may reveal minimal segmental infiltrates. Despite this more common picture, C pneumoniaepneumonia can be life threatening in patients older than 65 years. More recent serologic and anatomic data suggest that chronic C pneumoniae infections may play a role in atherosclerosis and in the progression of coronary artery disease. The clinical relevance of this information is not clear at this time.

BOX 67-8 Treatment of C pneumoniae Infections

First Choice

· Azithromycin, 500 mg/d for 10 d
OR

· Clarithromycin, 500 mg twice a day for 10–14 days
OR

· Levofloxacin, 500 mg every day for 10–14 days

Second Choice

· Tetracycline, 500 mg four times a day for 10–14 days
OR

· Doxycycline, 100 mg orally twice a day for 10 to 14 days

Pediatric Considerations

· Erythromycin, 50 mg/kg/d orally for 10–14 days
OR

· Clarithromycin, 15 mg/kg/d orally for 10 days

Diagnosis

Serological methods are commonly used for the diagnosis of C pneumoniae infections. They are rarely helpful in the acute setting, and they are mostly used for surveillance purposes. Complement fixation methods do not differentiate among infections caused by C trachomatis, C psittaci, and C pneumoniae. Microimmunofluorescence methods detect C pneumoniae-specific antibodies and are the approaches most commonly used in clinical practice. Acute and convalescent sera samples obtained ≥ 3–4 weeks apart should be analyzed in parallel. Isolation of this organism and PCR-based methods are not routinely performed outside research laboratories.

Treatment

C pneumoniae infection should be treated with a tetracycline, a macrolide, or a fluoroquinolone (Box 67-8).

The recommended treatment regimens for C pneumoniae infections in children include erythromycin (50 mg/kg/d for 10–14 days) or clarithromycin (15 mg/kg/d for 10 days). Some patients may require retreatment.

REFERENCES

Campbell LA, Kuo CC, Grayston JT: Chlamydia pneumoniae and cardiovascular disease. Emerg Infect Dis 1998; 4(4):571.

Centers for Disease Control and Prevention: Compendium of measures to control Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis),1998. Morb Mortal Wkly Rep 1998;47(RR-10):1.

Centers for Disease Control and Prevention: 1998 Guidelines for treatment of sexually transmitted diseases. Morb Mortal Wkly Rep 1998;47(RR-1):1.

Gaydos CA et al: Molecular amplification assays to detect chlamydial infections in urine specimens from high school female students and to monitor the persistence of chlamydial DNA after therapy. J Infect Dis 1998;177: 417.

Gregory DW, Schaffner W: Psittacosis. Sem Resp Infect 1997;12(1):7.

Kalman S et al: Comparative genomes of Chlamydia pneumoniae and C trachomatis. Nat Genet 1999;21:385.

Meier CR et al: Antibiotics and risk of subsequent first-time acute myocardial infarction. J Am Med Assoc 1999; 281:427.