94 CHANCrOiD
Image 26.1
Haemophilus ducreyi is a gram-negative coccobacillus, as shown in this preparation.
Courtesy of Centers for Disease Control and Prevention.
Image 26.2
ulcerative chancroid lesions with inflammation of the shaft and glans penis caused by Haemophilus ducreyi. Chancroid lesions are irregular in shape, painful, and soft (nonindurated) to touch. Courtesy of Hugh moffet, mD.
Image 26.3
Chancroid ulcer on the glans penis. Coinfection with syphilis or human herpesvirus occurs in as many as 10% of patients. Courtesy of Hugh moffet, mD.
Image 26.4
This adolescent black male presented with a chancroid lesion of the groin and penis affecting the ipsilateral inguinal lymph nodes. First signs of infection typically appear 3 to 5 days after exposure, although symptoms can take up to 2 weeks to appear. Courtesy of Centers for Disease Control and Prevention/J. Pledger.
Image 26.5
The penile ulcers on the penis of this adolescent white male proved to be due to chancroid, caused by Haemophilus ducreyi, and not syphilis as initially suspected. Chancroid can cause genital ulcers or inguinal buboes in the groin area. Courtesy of Centers for Disease Control and Prevention.
CHLAMYDOPHILA (FOrmErLy CHLAMYDIA) PNEUMONIAE 95
27
Chlamydial Infections Chlamydophila (formerly Chlamydia) pneumoniae
Clinical Manifestations
Patients can be asymptomatic or mildly to moderately ill with a variety of respiratory tract diseases, including pneumonia, acute bronchitis, prolonged cough, and, less com- monly, pharyngitis, laryngitis, otitis media, and sinusitis. In some patients, a sore throat precedes the onset of cough by a week or more.
The clinical course can be biphasic, culminat- ing in atypical pneumonia. Chlamydophila pneumoniae can present as severe community- acquired pneumonia in immunocompromised hosts and has been associated with acute exac- erbations in patients with cystic fibrosis and acute chest syndrome in children with sickle cell disease.
Physical examination may reveal nonexudative pharyngitis, pulmonary rales, and broncho- spasm. Chest radiography may reveal a variety of findings ranging from bilateral infiltrates to a single patchy subsegmental infiltrate. Illness can be prolonged, and cough can persist for 2 to 6 weeks or longer.
Etiology
C pneumoniae is an obligate intracellular bac- terium that is distinct antigenically, genetically, and morphologically from Chlamydia species, so it is grouped in the genus Chlamydophila.
Epidemiology
C pneumoniae infection is presumed to be transmitted from person to person via infected respiratory tract secretions. It is unknown whether there is an animal reservoir. The disease occurs worldwide, but in tropical and low-income countries, disease occurs earlier in life than in industrialized countries in tem- perate climates. The timing of initial infection peaks between 5 and 15 years of age. In the United States, approximately 50% of adults have C pneumoniae–serologic evidence of prior infection by age 20 years. Recurrent infection
is common, especially in adults. Clusters of infection have been reported in groups of chil- dren and young adults. There is no evidence of seasonality.
Incubation Period 21 days.
Diagnostic Tests
Serologic testing has been the primary means of diagnosing C pneumoniae infection but is problematic. The microimmunofluorescent antibody test is the most sensitive and specific serologic test for acute infection. A 4-fold increase in immunoglobulin (Ig) G titer between acute and convalescent sera is pre- ferred to diagnose acute infection, but an IgM titer of 1:16 or greater is also useful. Use of a single IgG titer in diagnosis of acute infection is not recommended because, during primary infection, IgG antibody may not appear until 6 to 8 weeks after onset of illness and increases within 1 to 2 weeks with reinfection. In pri- mary infection, IgM antibody appears approxi- mately 2 to 3 weeks after onset of illness but can be falsely positive because of cross-reactivity with other Chlamydia species or falsely nega- tive in cases of reinfection. Early antimicrobial therapy also may suppress antibody response.
C pneumoniae can be isolated from swab specimens obtained from the nasopharynx or oropharynx or from sputum, bronchoalveolar lavage, or tissue biopsy specimens. Specimens should be placed into appropriate transport media and stored at 4°C (39.2°F) until inocula- tion into cell culture; specimens that cannot be processed within 24 hours should be fro- zen and stored at –70°C (–94°F). Culturing C pneumoniae is difficult and often fails to detect the organism. Nasopharyngeal shedding can occur for months after acute disease, even with treatment. Because of the difficulty of accurately detecting C pneumoniae via culture, serologic testing, or immunohistochemistry testing, several types of polymerase chain reaction (PCR) assays have been developed.
Sensitivity and specificity of these different PCR techniques remain largely unknown.
A multiplex PCR assay has been cleared by
96 CHLAMYDOPHILA (FOrmErLy CHLAMYDIA) PNEUMONIAE
the US Food and Drug Administration for diagnosis of C pneumoniae using nasopharyn- geal samples. The test appears to have high sen- sitivity and specificity.
Treatment
Most respiratory tract infections thought to be caused by by C pneumoniae are treated empirically. For suspected C pneumoniae infections, treatment with macrolides (eg,
azithromycin, erythromycin, clarithromycin) is recommended. Tetracycline or doxycycline can be used in children older than 7 years.
Newer fluoroquinolones (levofloxacin and moxifloxacin) are alternative drugs for patients who are unable to tolerate macrolide antibiot- ics but should not be used as first-line treat- ment. Therapy is continued to 10 to 14 days, except for azithromycin, when 5 days is typi- cally adequate.
CHLAMYDOPHILA (FOrmErLy CHLAMYDIA) PSITTACI 97
28
Chlamydophila (formerly Chlamydia) psittaci
(Psittacosis, Ornithosis, Parrot Fever) Clinical Manifestations
Psittacosis (ornithosis) is an acute respiratory tract infection with systemic symptoms and signs including fever, nonproductive cough, headache, and malaise. Less common symp- toms are pharyngitis, diarrhea, and altered mental status. Extensive interstitial pneumonia can occur, with radiographic changes charac- teristically more severe than would be expected from chest examination findings. Endocarditis, myocarditis, pericarditis, thrombophlebitis, nephritis, hepatitis, and encephalitis are rare complications. Recent studies have suggested an association with ocular adnexal marginal zone lymphomas involving orbital soft tissue, lacrimal glands, and conjunctiva.
Etiology
Chlamydophila psittaci is an obligate intra- cellular bacterium that is distinct antigenically, genetically, and morphologically from Chla
mydia species and, following reclassification, is grouped in the genus Chlamydophila.
Epidemiology
Birds are the major reservoir of C psittaci. The term psittacosis commonly is used, although the term ornithosis more accurately describes the potential for nearly all domestic and wild birds to spread this infection, not just psitta- cine birds (eg, parakeets, parrots, macaws). In the United States, psittacine birds, pigeons, and turkeys are important sources of human disease. Importation and illegal trafficking of exotic birds is associated with an increased incidence of human disease because shipping, crowding, and other stress factors may increase shedding of the organism among birds with latent infection. Infected birds, whether healthy appearing or obviously ill, can trans- mit the organism. Infection is usually acquired by inhaling aerosolized excrement or respira- tory secretions from the eyes or beaks of infected birds. Handling of plumage and mouth-to-beak contact are the modes of
exposure described most frequently, although transmission has been reported through expo- sure to aviaries, bird exhibits, and lawn mow- ing. Excretion of C psittaci from birds can be intermittent or continuous for weeks or months. Pet owners and workers at poultry slaughter plants, poultry farms, and pet shops are at increased risk of infection. Laboratory personnel working with C psittaci are also at risk. Psittacosis is worldwide in distribution and tends to occur sporadically in any season.
Although rare, severe illness and abortion have been reported in pregnant women.
Incubation Period 5 to 14 days (may be longer).
Diagnostic Tests
A confirmed diagnosis of psittacosis requires a clinically compatible illness with fever, chills, headache, cough, and myalgias, plus laboratory confirmation by one of the following: isolation of C psittaci from respiratory tract specimens or blood, or 4-fold or greater increase in immu- noglobulin (Ig) G by complement fixation (CF) or a titer of 1:32 with microimmunofluores- cence (MIF) against C psittaci between paired acute- and convalescent-phase serum speci- mens obtained at least 2 to 4 weeks apart. A probable case of psittacosis requires a clinically compatible illness and either supportive sero- logic test results (eg, C psittaci IgM ≥1:16) or detection of C psittaci DNA in a respiratory tract specimen by polymerase chain reaction assay. For serologic testing, MIF is more sensi- tive and specific than CF, but CF and MIF can cross-react with other chlamydial species and should be interpreted cautiously. Additionally, nucleic acid amplification tests have been developed that can distinguish C psittaci from other chlamydial species and are under investi- gation for detection of C psittaci from human clinical samples. Treatment with antimicrobial agents may suppress the antibody response.
Culturing the organism is recommended; how- ever, it is difficult and should be attempted only by experienced personnel in laboratories where strict containment measures to prevent spread of the organism are used during collection and handling of all specimens because of occupa- tional and laboratory safety concerns.
98 CHLAMYDOPHILA (FOrmErLy CHLAMYDIA) PSITTACI
Treatment
Tetracycline or doxycycline is the drug of choice. Erythromycin and azithromycin are alternative agents and are recommended for children younger than 8 years and pregnant
women. Therapy should be for a minimum of 10 days and for 10 to 14 days after fever abates.
In patients with severe infection, intravenous doxycycline can be considered.
Image 28.1
This direct fluorescent antibody stained mouse brain impression smear reveals the presence of the bacterium Chlamydophila psittaci. Psittacosis is acquired by inhaling dried secretions from birds infected with C psittaci. Although all birds are susceptible, pet birds and poultry are most frequently involved in transmission to humans.
Courtesy of Courtesy of Centers for Disease Control and Prevention/vester Lewis, mD.
Image 28.2
Chlamydophila psittaci pneumonia in a 16-year- old girl with a cough of 3 weeks’ duration. The family had several parrots in the home that were purchased from a roadside stand near the Texas- mexico border. interstitial pneumonia, most prominent in the lower lobe of the left lung, is shown. Complement fixation titer for C psittaci is 1:128. Copyright David Waagner.
Image 28.3
Lateral chest radiograph of the patient in image 28.2. most domestic and wild birds can transmit Chlamydophila psittaci. Copyright David Waagner.
CHLAMYDIA TRACHOMATIS 99
29
Chlamydia trachomatis
Clinical Manifestations
Chlamydia trachomatis is associated with a range of clinical manifestations, including neonatal conjunctivitis, nasopharyngitis, and pneumonia in young infants; genital tract infection; lymphogranuloma venereum (LGV); and trachoma.
• Neonatal chlamydial conjunctivitis is char- acterized by ocular congestion, edema, and discharge developing a few days to several weeks after birth and lasting for 1 to 2 weeks and sometimes longer. In contrast to tra- choma, scars and pannus formation are rare.
• Pneumonia in young infants is usually an afebrile illness of insidious onset occurring between 2 and 19 weeks after birth. A repe titive staccato cough, tachypnea, and rales in an afebrile 1-month-old are charac- teristic but not always present. Wheezing is uncommon. Hyperinflation usually accompanies infiltrates seen on chest radio- graphs. Nasal stuffiness and otitis media may occur. Untreated disease can linger or recur. Severe chlamydial pneumonia has occurred in infants and some immuno- compromised adults.
• Genitourinary tract manifestations, such as vaginitis in prepubertal girls; urethritis, cervicitis, endometritis, salpingitis, proctitis, and perihepatitis (Fitz-Hugh–Curtis syn- drome) in postpubertal females; urethritis, epididymitis, and proctitis in males; and Reiter syndrome (arthritis, urethritis, and bilateral conjunctivitis), can occur. Infection can persist for months to years. Reinfection is common. In postpubertal females, chla- mydial infection can progress to pelvic inflammatory disease and can result in ectopic pregnancy, infertility, or chronic pelvic pain.
• Lymphogranuloma venereum is classically an invasive lymphatic infection with an ini- tial ulcerative lesion on the genitalia accom- panied by tender, suppurative inguinal or femoral lymphadenopathy that is typically unilateral. The ulcerative lesion often has
resolved by the time the patient seeks care.
Proctocolitis may occur in women or men who engage in anal intercourse. Symptoms can resemble those of inflammatory bowel disease, including mucoid or hemorrhagic rectal discharge, constipation, tenesmus, or anorectal pain. Stricture or fistula for- mation can follow severe or inadequately treated infection.
• Trachoma is a chronic follicular kerato- conjunctivitis with neovascularization of the cornea that results from repeated and chronic infection. Blindness secondary to extensive local scarring and inflammation occurs in 1% to 15% of people with trachoma.
Etiology
C trachomatis is an obligate intracellular bacterium with at least 18 serologic variants (serovars) divided between the following bio- logic variants (biovars): oculogenital (serovars A–K) and LGV (serovars L1, L2, and L3). Tra- choma usually is caused by serovars A through C, and genital and perinatal infections are caused by B and D through K.
Epidemiology
C trachomatis is the most common reportable sexually transmitted infection in the United States, with high rates among sexually active adolescents and young adult women. A signifi- cant proportion of patients are asymptomatic, providing an ongoing reservoir for infection.
Prevalence of the organism is consistently highest among adolescent and young adult women. Among all 14- to 25-year-olds partici- pating in the 2008 National Health and Nutri- tion Examination Survey, prevalence was 3.3%
among females and 1.7% among males. Racial disparities are significant. The estimated preva- lence among non-Hispanic black people (6.7%) was higher than the estimated prevalence among non-Hispanic white people (0.3%) and Mexican American people (2.4%). Among males who have sex with males screened for rectal chlamydial infection, positivity ranges from 3% to 10%. Oculogenital serovars of C trachomatis can be transmitted from the genital tract of infected mothers to their new- borns during birth. Acquisition occurs in approximately 50% of neonates born vaginally
100 CHLAMYDIA TRACHOMATIS
to infected mothers and in some neonates born by cesarean delivery with membranes intact.
The risk of conjunctivitis is 25% to 50% and the risk of pneumonia is 5% to 30% in infants who contract C trachomatis. The nasopharynx is the anatomic site most commonly infected.
Genital tract infection in adolescents and adults is transmitted sexually. The possibility of sexual abuse should always be considered in prepubertal children beyond infancy who have vaginal, urethral, or rectal chlamydial infection. Sexual abuse is not limited to prepu- bertal children, and chlamydial infections can result from sexual abuse or assault in postpu- bertal adolescents as well.
Asymptomatic infection of the nasopharynx, conjunctivae, vagina, and rectum can be acquired at birth. Nasopharyngeal cultures have been observed to remain positive for as long as 28 months and vaginal and rectal cultures for more than 1 year in infants and children with infection acquired at birth.
Infection is not known to be communicable among infants and children. The degree of contagiousness of pulmonary disease is unknown but seems to be low.
Lymphogranuloma venereum biovars are worldwide in distribution but are particularly prevalent in tropical and subtropical areas.
Although disease rarely occurs in the United States, outbreaks of LGV have been reported among men who have sex with men. Infection is often asymptomatic in females. Perinatal transmission is rare. Lymphogranuloma vene- reum is infectious during active disease. Little is known about the prevalence or duration of asymptomatic carriage.
Although rarely observed in the United States since the 1950s, trachoma is the leading infec- tious cause of blindness worldwide, causing up to 3% of the world’s blindness. It generally is confined to poor populations in resource- limited nations of Africa, the Middle East, Asia, Latin America, the Pacific Islands, and remote aboriginal communities in Australia.
Trachoma is transmitted by transfer of ocular discharge. Predictors of scarring and blindness for trachoma include increasing age and con- stant, severe trachoma.
Incubation Period
Variable, depending on infection type; usually at least 1 week.
Diagnostic Tests
C trachomatis urogenital infection in females can be diagnosed by testing first catch urine or swab specimens from the endocervix or vagina. Diagnosis of C trachomatis urethral infection in males can be made by testing a urethral swab or first catch urine specimen.
Nucleic acid amplification tests (NAATs) are the most sensitive tests for these speci- mens and are the recommended tests for C trachomatis detection.
For detecting C trachomatis infections of the genital tract among postpubescent individu- als, older nonculture tests and non-NAATs, such as DNA probe, direct fluorescent antibody tests, or enzyme immunoassay tests, have inferior sensitivity and specificity charac- teristics and are no longer recommended for C trachomatis testing. In the evaluation of prepubescent children for possible sexual assault, the Centers for Disease Control and Prevention recommends culture for C tracho
matis of a specimen collected from the rectum in boys and girls and from the vagina in girls.
A meatal specimen should be obtained from boys for chlamydia testing if urethral discharge is present.
Serum anti–C trachomatis antibody concen- trations are difficult to determine, and only a few clinical laboratories perform this test. In children with pneumonia, an acute microim- munofluorescent serum titer of C trachomatis–
specific immunoglobulin M of 1:32 or greater is diagnostic. Diagnosis of LGV can be supported but not confirmed by a positive result (ie, titer
>1:64) on a complement-fixation test for chla- mydia or a high titer (typically >1:256, but this can vary by laboratory) on a microimmuno- fluorescent serologic test for C trachomatis.
However, most available serologic tests in the United States are based on enzyme immuno- assay tests and might not provide a quantitative titer-based result.
Diagnosis of genitourinary tract chlamydial disease in a child should prompt examination for other sexually transmitted infections,
CHLAMYDIA TRACHOMATIS 101
including syphilis, gonorrhea, and HIV, and investigation of sexual abuse or assault. In the case of a neonate or an infant, because cultures can be positive for at least 12 months after infection acquired at birth, evaluation of the mother is also advisable.
Diagnosis of ocular trachoma is usually made clinically in countries with endemic infection.
Treatment
• Newborns and infants with chlamydial con- junctivitis or pneumonia are treated with oral erythromycin base or ethylsuccinate for 14 days or with azithromycin for 3 days.
Because the efficacy of erythromycin therapy is approximately 80% for both of these con- ditions, a second course may be required, and follow-up of infants is recommended.
A diagnosis of C trachomatis infection in an infant should prompt treatment of the mother and her sexual partner(s). The need for treatment of infants can be avoided by screening pregnant women to detect and treat C trachomatis infection before delivery.
An association between orally administered erythromycin and infantile hypertrophic pyloric stenosis (IHPS) has been reported in newborns and infants younger than 6 weeks.
The risk of IHPS after treatment with other macrolides (eg, azithromycin, clarithromy- cin) is unknown, although IHPS has been reported after use of azithromycin. Because confirmation of erythromycin as a contribu- tor to cases of IHPS will require additional investigation and alternative therapies are not as well studied, erythromycin remains the drug of choice. Physicians who prescribe erythromycin to newborns should inform parents about the signs and potential risks of developing IHPS.
Neonates born to mothers known to have untreated chlamydial infection are at high risk of infection; however, prophylactic antimicrobial treatment is not recom- mended. Neonates should be monitored clinically to ensure appropriate treatment if infection develops. If adequate follow-up cannot be ensured, preemptive therapy should be considered.
• For uncomplicated C trachomatis anogeni- tal tract infection in adolescents or adults, oral doxycycline for 7 days or single-dose azithromycin is recommended. Alternatives include oral erythromycin base, erythromy- cin ethylsuccinate, ofloxacin, levofloxacin, or doxycycline delayed-release daily for 7 days.
For children who weigh less than 45 kg, the recommended regimen is oral erythromycin base or ethylsuccinate for 14 days. For chil- dren who weigh 45 kg or more but who are younger than 8 years, the recommended regimen is azithromycin, in a single oral dose. For children 8 years and older, the recommended regimen is azithromycin as a single oral dose or doxycycline for 7 days.
For pregnant women, the recommended treatment is azithromycin as a single oral dose. Amoxicillin or erythromycin base for 7 days are alternative regimens. Doxycycline, ofloxacin, and levofloxacin are contraindi- cated during pregnancy.
• Follow-up testing. Test of cure is not recommended for nonpregnant adult or adolescent patients treated for uncompli- cated chlamydial infection unless compli- ance is in question, symptoms persist, or reinfection is suspected. Test of cure (prefer- ably by NAAT) is recommended 3 to 4 weeks after treatment of pregnant women. Because some of these regimens for pregnant women may not be highly efficacious, a second course of therapy may be required. Reinfec- tion is common after initial infection and treatment, and all infected adolescents and adults should be tested for C trachomatis 3 months following initial treatment. If retesting at 3 months is not possible, retest whenever patients next present for health care in the 12 months after initial treatment.
• For LGV, doxycycline for 21 days is the preferred treatment for children 8 years and older, and erythromycin for 21 days is an alternative regimen; azithromycin for 3 weeks is probably effective but has not been as well studied.
• Treatment of trachoma is azithromycin as a single oral dose as recommended by the World Health Organization and includes all household contacts of patients.