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Chapter Infective Syndromes of Genital Tract 77...

Chapter Infective Syndromes of Genital Tract 77 Chapter Preview „„Genital Tract Infections Common in zz Genito-ulcerative Disease „„Genital Tract Infections in Females Both Sexes zz Urethritis „„Genital Tract Infections in Males Sexually transmitted infections Table 77.1: Causative agents of sexually transmitted infections. The sexually transmitted infections (STIs) are a group of Agents causing local manifestations (genital tract infections) communicable diseases which are transmitted by sexual In both sexes: https://t.me/docinmayking contact. Causative agents of STIs may be classified into two Genito-ulcerative disease: groups (Table 77.1): Syphilis: Caused by Treponema pallidum 1. Agents causing local manifestations—called genital Chancroid: Caused by Haemophilus ducreyi Genital herpes: Caused by herpes simplex viruses tract infections Lymphogranuloma venereum: Caused by Chlamydia trachomatis „„ Lesions common to both sexes: Such as genital Donovanosis: Caused by Klebsiella granulomatis ulcers, urethritis, and anorectal lesions Urethritis: „„ Female genital tract infections: Such as vulvovaginitis, Gonococcal urethritis: Caused by Neisseria gonorrhoeae cervicitis and others Non-gonococcal urethritis (NGU): Caused by ¾¾ Chlamydia trachomatis (D-K) „„ Male genital tract infections: Such as prostatitis, ¾¾ Genital mycoplasmas: Ureaplasma urealyticum, Mycoplasma epididymitis, and orchitis. genitalium, M. hominis 2. Agents causing systemic manifestations without ¾¾ Herpes simplex virus producing local manifestations (e.g. HIV, hepatitis B and ¾¾ Candida albicans C)—these infections are discussed under the systems ¾¾ Trichomonas vaginalis which they primarily affect. Other genital tract infections common to both sexes Genital tuberculosis: Caused by M. tuberculosis Anorectal lesions: Genito-Ulcerative disease ¾¾ Proctitis: Caused by HSV, gonococcus, C. trachomatis ¾¾ Anogenital warts: Caused by human papilloma virus Genito-ulcerative disease comprises of five important STIs— In females only: syphilis, chancroid, genital herpes, lymphogranuloma Vulvovaginitis: Bacterial vaginosis, trichomoniasis and venereum and donovanosis. candidiasis ™™ It is important to clinically differentiate them from each Mucopurulent cervicitis caused by gonococcus, C. trachomatis other so that appropriate treatment can be initiated Pelvic inflammatory disease: Presents as— ™™ Differentiation is based on the characteristic of ¾¾ Endometritis, salpingitis, oophoritis, tubo-ovarian abscess genital ulcer such as pain, induration, and associated ¾¾ Extension to peritoneum can lead to peritonitis, pelvic abscess lymphadenopathy (Table 77.2). and perihepatitis Infections after gynecologic surgery Infections in pregnancy/postpartum Syphilis (TREPONEMA PALLIDUM) In males only: Treponema pallidum is the causative agent of an ancient Prostatitis, epididymitis, and orchitis sexually transmitted infection (STI) ‘syphilis’. The name Agents causing systemic manifestations, no local lesions pallidum refers to its pale-staining property. It was HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) discovered by Schaudinn and Hoffmann in 1905. Leptospira; the latter two have been discussed in Genus Description Chapter 32. Spirochetes are thin, flexible, elongated spirally coiled Treponemes are slender spirochetes with fine spirals helical bacilli. They include Treponema, Borrelia and having pointed ends (trepos, meaning ‘turn’ and nema,  Chapter 77  Infective Syndromes of Genital Tract 757 Table 77.2: Comparison of manifestations of genito-ulcerative diseases. Features Syphilis Genital Herpes Chancroid LGV Donovanosis Incubation period 9–90 days 2–7 days 1–14 days 3 days–6 weeks 1–4 weeks (up to 6 months) Genital ulcer Painless, single, Painful, multiple, Painful, soft, usually Painless, firm single Painless, single/multiple, indurated bilateral, tiny multiple, purulent, lesion beefy-red ulcer, bleeds vesicular ulcers bleeds easily readily Lymphadenopathy Painless, non- Painful, firm, often Painful, soft, marked Painful and soft, Absent (pseudobubo indurated (firm), bilateral with initial swelling leads to bubo unilateral may be present due to bilateral episode formation, unilateral subcutaneous swelling) Treatment Penicillin Acyclovir Azithromycin Doxycycline Azithromycin (single dose) (7–14 days) (single dose) (21 days) ( 7 days) meaning ‘thread’). Most of them are commensals in mouth manifestations can mimic many other diseases. Clinically, and genitalia. Only a few species are pathogenic to men, patients suffering from syphilis pass through four stages if which can be divided into two groups. left untreated: primary, secondary, latent and tertiary (or 1. Sexually-transmitted: Treponema pallidum—it causes late) stages. Apart from this, if transmitted vertically, the syphilis, discussed below newborn babies develop a congenital form of syphilis. 2. Nonvenereal treponematosis: T. pertenue, T. endemicum and T. carateum Primary Syphilis https://t.me/docinmayking „„ They are almost identical with T. pallidum in their Primary syphilis is characterized by: morphology, antigenic structure and in genetic ™™ Primary (or hard) chancre: It is characterized by single composition painless hard indurated ulcer; covered by thick exudate „„ However, they differ from T. pallidum, being rich in spirochetes. The most common sites are penis transmitted by non-sexual mode (by direct contact) (in males), cervix or labia (in females), and anal canal, and produce non-genital cutaneous manifestations rectum or mouth (in homosexuals) (Fig. 77.1) (discussed in Chapter 55). ™™ Regional (usually inguinal) lymphadenopathy appears within 1 week of onset of skin lesions. Lymph nodes are Pathogenesis of Syphilis painless firm, non-suppurative, and often bilateral Syphilis is one of the ancient sexually transmitted infection ™™ The chancre generally heals within 4–6 weeks (range 2–12 known since fifteenth century. Name was derived from a weeks), but lymphadenopathy may persist for months famous poem in the year 1530 which described a legend ™™ If acquired by non-venereal mode, then the primary of a shepherd boy named Syphilus, who had suffered from syphilis is presented as follows: the disease. „„ If transmitted by direct contact→the primary chancre ™™ Mode of transmission: Venereal syphilis is acquired is extragenital, usually on the fingers by sexual contact. However, it can also be transmitted „„ If transmitted by blood transfusion→the primary by non-venereal modes such as direct contact, blood chancre does not occur. transfusion or transplacental transmission ™™ Spread: T. pallidum rapidly penetrates through the minute abrasions on the skin or mucosa and, within a few hours, enters the lymphatics and blood to produce systemic infection and metastatic foci long before the appearance of a primary lesion. Blood is infectious even during the incubation period or in the early stage of syphilis ™™ Incubation period can range from 10 to 90 days and is inversely proportional to the number of organisms inoculated. The median incubation period in humans is about 21 days which corresponds to an average inoculum of 500–1000 infectious organisms. Clinical Manifestations of Syphilis Approximately, 30% of persons who have sexual exposure Fig. 77.1: Primary syphilis (hard chancre). with an infected partner develop syphilis. This disease Source: Public Health Image Library, ID# 6803, Dr/M. Rein/Centers for Disease has been called as “The Great Pretender”, as its clinical Control and Prevention (CDC), Atlanta (with permission). 758 Section 10  Urogenital Tract Infections A B C Figs 77.2A to C: Clinical manifestations of secondary syphilis: A. Skin rashes; B. Condylomata lata; C. Mucosal patch. Source: Public Health Image Library/A. ID# 6808; B. ID# 4098; C. ID# 4816/Centers for Disease Control and Prevention (CDC), Atlanta (with permission). Secondary Syphilis ™™ Neurosyphilis: Common manifestations include— Secondary syphilis usually develops 6–12 weeks after the chronic meningitis, vasculitis, general paresis of insane healing of primary lesion. Skin and mucous membranes and tabes dorsalis (Chapter 71 for detail) ™™ Cardiovascular syphilis: Characterized by aneurysm of are commonly affected and characterized by: ™™ Skin rashes (palms and soles Fig. 77.2A) ascending aorta and aortic regurgitation. https://t.me/docinmayking ™™ Condylomata lata (mucocutaneous papules which Congenital Syphilis coalesce to form large pink to grey lesions in warm moist intertriginous areas such as perianal region, vulva, and Mother-to-fetus transmission can lead to development scrotum) (Fig. 77.2B) of various congenital manifestations, discussed in ™™ Mucous patches (superficial mucosal erosions; Figure Chapter 79. 77.2C) Epidemiology ™™ Generalized lymphadenopathy is seen. Chancre may also persist in up to 1/3rd cases. In 1940s, syphilis was considered as the most common type of genital ulcer. With increased education on safe Latent Syphilis sex practices, and widespread use of broad-spectrum Secondary lesions usually subside within 2–6 weeks, antibiotics to treat STI-related syndromes; the incidence and the infection proceeds to latent syphilis; which is of syphilis has declining over past few decades. ™™ Incidence: Syphilis still remains a significant health characterized by absence of clinical manifestations of syphilis with positive serological tests for syphilis and problem globally; the number of new infections is normal CSF findings. estimated to be 11 million per year globally ™™ Latent syphilis may be early latent syphilis (occurs ™™ Most affected regions: The regions that are most affected within first year after infection) and late latent syphilis include sub-Saharan Africa, South America, China, and (occurs after the first year of infection) Southeast Asia ™™ Patients are still infectious transmitting the infection ™™ In pregnancy: Worldwide, 1.4 million cases of syphilis either by bloodstream or in utero occur among pregnant women, with 5 lakh adverse ™™ Latent syphilis may have one of the following fates: pregnancy outcomes annually. „„ Persistent lifelong infection (common) L aboratory diagnosis Syphilis „„ Development of late syphilis (rare) „„ Spontaneous cure. Microscopy ‰‰ Dark ground microscopy Late or Tertiary Syphilis ‰‰ Direct IF staining for T. pallidum (DFA-TP) ‰‰ Silver impregnation method Several decades after the initial infection, about one-third ¾¾ Levaditi stain (for tissue section) of untreated patients develop tertiary syphilis, of which ¾¾ Fontana stain (smear) 15% develop gummatous lesions, about 10% develop Culture: Not cultivable, maintained in rabbit testes cardiovascular lesions and remaining 10% develop Serology (antibody detection) neurosyphilis. The latter two stages are sometimes ‰‰ Non-treponemal or STS (standard tests for syphilis): Reagin classified as quaternary syphilis. antibodies are detected by using cardiolipin antigen ™™ Gumma (late benign syphilis): Gummas are locally ¾¾ VDRL (Venereal disease research laboratory) test destructive granulomatous lesions. They can occur in ¾¾ RPR (Rapid plasma reagin) any organ but most commonly seen in bone and skin Contd...  Chapter 77  Infective Syndromes of Genital Tract 759 Contd... ™™ Multiple specimens should be examined on three consecutive days before declaring DGM to be negative L aboratory diagnosis Syphilis ™™ Saprophytic spirochetes: It is difficult to differentiate TRUST (toluidine red unheated serum test) ¾¾ T. pallidum from other saprophytic spirochetes of the USR (Unheated serum reagin test). ¾¾ genital area, such as T. refringens (shows very active ‰‰ Specific/Treponemal test: Specific antibodies are detected by serpentine-like movement), and T. phagedenis (shows using T. pallidum antigens jerky movement). Differentiation is based on size, spiral ¾¾ TPI (Treponema pallidum immobilization test) character and motility. ¾¾ FTA-ABS (Fluorescent treponemal antibody absorption test) Direct Fluorescent Antibody Staining for T. pallidum ¾¾ TPA (T. pallidum agglutination test) (DFA-TP) ¾¾ TPHA (T. pallidum hemagglutination test) ¾¾ TPPA (T. pallidum particle agglutination test). Smear made from the exudate or tissue sections is stained Polymerase chain reaction (PCR) with fluorescent-labelled monoclonal antibody targeted against T. pallidum surface antigens. Laboratory Diagnosis of Syphilis ™™ T. pallidum appears as distinct, sharply outlined, apple Laboratory diagnosis of syphilis consists of demonstration green fluorescent colored bacilli (Fig. 77.3B) of treponemes, detection of antibodies and PCR. ™™ Sensitivity of DFA-TP test approaches 100% when smear made from fresh lesions are examined. Direct Microscopy (Demonstration of Treponemes) Silver Impregnation Staining Treponemes can be demonstrated from the superficial https://t.me/docinmayking lesions of primary, secondary and congenital syphilis. Treponema do not take up ordinary stains as they are Surface of the chancre is cleaned with saline, gentle extremely thin and delicate (Fig. 77.3C). pressure is applied at the base of the lesion, and a drop of ™™ However, silver impregnation methods can be used to exudate is collected on a slide. increase their thickness ™™ Treponemes reduce silver nitrate to metallic silver that Dark Ground Microscopy (DGM) is deposited on the surface, making them thicker Treponemes cannot be visualized by light microscope but ™™ Levaditi stain is used for staining tissue section and Fon- can be seen by examining the wet film of specimen under tana stain is used for staining smears made from exudates. dark ground (DGM) or phase contrast microscope. ™™ Under DGM: T. pallidum appears as slender, flexible, Cultivation spirally coiled bacilli with tapering ends, measuring Pathogenic treponemes including T. pallidum cannot be 6–20 μm in length and contains 6–20 spirals (Fig. 77.3A) grown in artificial culture media but are maintained by ™™ Motility: T. pallidum shows typical: (i) slow to rapid subcultures in susceptible animals such as rabbit testes flexion-extension type of movement with (ii) rotation (e.g. Nichols strain). around its longitudinal axis (corkscrew motility), (iii) rotation may be accompanied by a soft bending at right Serology (Antibody Detection) angle to the midpoint As microscopy is difficult and culture methods are not ™™ The sensitivity of DGM approaches 80% with a detection available, antibody detection methods are of paramount limit of 104 bacilli/mL importance in the diagnosis of syphilis. A B C Figs 77.3A to C: Direct microscopy of T. pallidum: A. Dark ground microscope; B. Direct fluorescent antibody staining for T. pallidum (DFA-TP); C. Silver impregnation method. Source: Public Health Image Library, A. ID# 2043; B. ID# 14967/Dr Russell; C. ID# 836, Centers for Disease Control and Prevention (CDC), Atlanta (with permission). 760 Section 10  Urogenital Tract Infections Depending upon the type of antigen used, three types of tests are available to detect antibodies in patient’s sera: ™™ Non-treponemal tests: Detect non-specific reagin antibody by using cardiolipin antigen derived from bovine heart ™™ Treponemal tests: Detect species-specific antibody by using T. pallidum specific antigen; which is polysaccharide in nature. Non-treponemal or Lipoidal Tests or STS (Standard Tests for Syphilis) Non-treponemal tests (or lipoidal tests) detect a characteristic non-specific antibody (called reagin antibody) in the sera of syphilitic patients by using cardiolipin antigen extracted from beef hea­rt. A ™™ Cardiolipin antigen is chemically a diphosphatidyl glycerol. Similar lipid haptens have been detected on the surface of T. pallidum ™™ Such reagin antibodies are IgG or rarely IgM type and are distinct from the IgE class of reagin antibodies seen https://t.me/docinmayking in type I hypersensitivity reactions. B Examples of non-treponemal tests include various slide flocculation tests such as: ™™ Venereal Disease Research Laboratory (VDRL) Figs 77.4A and B: A. VDRL slide; B. VDRL test results. Source: Department of Microbiology, JIPMER, Puducherry (with permission). ™™ Rapid Plasma Reagin (RPR) ™™ Unheated Serum Reagin (USR) ™™ Toluidine Red Unheated Serum Test (TRUST). where as VDRL is preferred when samples are tested in VDRL and RPR are the widely used tests and therefore batches (large sample load) ™™ Results can be read in naked eyes, without the need of are described below. a microscope, as the clumps formed are bigger in size Venereal Disease Research Laboratory (VDRL) ™™ It can only be used for detecting antibodies in blood; This test was named after Venereal Disease Research not in CSF Laboratory (VDRL), New York, where the test was ™™ It is more expensive than VDRL. developed. It works on the principle of precipitation (slide flocculation) test. Advantages of Non-treponemal Tests ™™ Procedure: 50 μL of patient’s serum (heat inactivated) is ™™ Non-treponemal tests are recommended to monitor the mixed with a drop of VDRL antigen on a concave slide, response to treatment which is then mixed by rotating the slide for 4 minutes ™™ Neurosyphilis: VDRL can also be used to detect CSF (Figs 77.4A and B) antibodies ™™ Result: Positive test (i.e. reactive) is indicated by ™™ Reagin antibody becomes detectable 7–10 days after formation of medium to large clumps of antigen antibody the appearance of primary chancre (or 3–5 weeks after complexes; visualized by focusing the slide under acquiring the infection) microscope (10x) ™™ Utility: The sensitivity of nontreponemal tests varies ™™ CSF antibodies: VDRL test can also be performed on from 78 to 85% in primary stage, 100% in secondary CSF specimen to detect antibodies stage, 71–73% in late stage and the specificity is around ™™ Uses: VDRL test is cheaper and preferred as a screening 98–99%. test for laboratory with higher sample load and for batch Disadvantages of Non-treponemal Tests testing (e.g. antenatal screening) and also to monitor Biological false-positive (BFP) reactions: Non- treatment response. treponemal tests may give a false-positive result in the Rapid Plasma Reagin (RPR) absence of syphilis and is also not due to technical faults. RPR is another slide flocculation test using disposable The incidence of BFP is generally 1–2%. plastic cards having clearly defined circles. It is similar to ™™ This is because reagin antibodies may also be found in VDRL test with some differences such as: patients with unrelated diseases such as lepromatous ™™ RPR antigen has a prolonged shelf-life, therefore it is leprosy, relapsing fever, malaria, viral hepatitis, HIV, preferred to test individual sample (less sample load); pregnancy and IV drug abusers  Chapter 77  Infective Syndromes of Genital Tract 761 ™™ In these conditions, the reagin antibodies are induced treponemal test (for confirmation) for serodiagnosis of against lipid haptens released from the damaged host syphilis. However, in area with high-prevalence for syphilis, tissues which may mimic cardiolipin antigens. a strategy of reverse algorithm may be found cost-effective Other disadvantages include: where a treponemal test is performed first, followed by ™™ Prozone phenomena: If antibody titer in patient’s sera non-treponemal test. is high, it may lead to false negative result hence it is Testing for syphilis in pregnancy: Every pregnant woman essential to test sera in dilutions should undergo a non-treponemal screening test at her ™™ Sensitivity of non-treponemal tests is low in late stage first antenatal visit and, if there is high-risk of exposure, of syphilis. VDRL-CSF is more reliable for neurosyphilis again retested at the third trimester and at delivery. than VDRL test of serum. Treponemal or Specific Tests Syphilis and HIV Both syphilis and HIV affect each other’s pathogenesis. Treponemal tests aim at detecting T. pallidum specific ‰‰ Genital syphilis facilitates the transmission of HIV through antibodies in patient’s sera by using either live or killed T. the abraded mucosa (2 to 5 fold increased risk) pallidum or their antigenic extract. The various examples ‰‰ Patient with HIV, if develops syphilis later→there is rapid include: progression to late stages of syphilis and neurological ™™ TPI (T. pallidum immobilization test): Uses live involvement even after treatment of primary or secondary actively motile T. pallidum (Nichols strain); which syphilis. become immobilized after they combine with specific Problems in the diagnosis of syphilis in HIV infected people antibodies are: https://t.me/docinmayking ‰‰ Confusing clinical signs and symptoms ™™ FTA-ABS (Fluorescent treponemal antibody ¾¾ Clinical overlap with different stages of syphilis may be absorption test): Patient’s serum is layered on a slide present which is previously coated with killed T. pallidum. ¾¾ CNS invasion and ocular manifestations (posterior Fluorescent labeled anti-human immunoglobulin is uveitis) are common presentation. added and then slide is examined under fluorescent ‰‰ Lack of serologic response in a patient with a clinically microscope confirmed case of active syphilis „„ It is highly sensitive and specific in all the stages of ‰‰ Unusually high titers in non-treponemal tests perhaps as a syphilis result of B cell activation „„ It is the first serological test to be positive following ‰‰ Failure of non-treponemal test titers to decline even after infection treatment with standard regimens ‰‰ Disappearance of treponemal test reactivity over time. „„ IgM-FTA-ABS test is a modification that detects only IgM antibodies and therefore is useful for congenital syphilis T Reatment Syphilis „„ It can also be used to detect CSF antibodies. ‰‰ Penicillin is the drug of choice for all the stages of syphilis: ™™ Tests that use extract of T. pallidum ¾¾ Primary, secondary, or early latent syphilis: single dose of „„ TPHA (T. pallidum hemagglutination test) Penicillin G is given „„ TPPA (T. pallidum particle agglutination test) ¾¾ Late latent CVS or benign tertiary stage: penicillin G is „„ Western blot and enzyme immunoassay. given single dose weekly for 3 weeks The sensitivity of treponemal tests varies from 84 to 90 % ¾¾ Neurosyphilis or abnormal CSF in any stage or associated in primary stage, 100% in secondary stage, 94–96% in late HIV-aqueous crystalline or procaine penicillin G is given stage and the specificity is around 97–99%. for 10–14 days. Consider re-treatment if non-treponemal titres in CSF, do not decrease four fold within 2 years of Molecular Methods completion of treatment. ‰‰ Alternative drug is used in patients with penicillin allergy: PCR-based techniques are available to amplify T. pallidum ¾¾ For primary, secondary, latent, CVS or benign tertiary specific genes, such as gene coding for 47-kDa surface syphilis—tetracycline is recommended antigen (lipoprotein) and 39-kDa basic membrane protein. ¾¾ For neurosyphilis or in pregnancy or associated HIV— PCR is of paramount importance in the diagnosis of desensitization to penicillin has to be done, following congenital and neurosyphilis. which penicillin is administered. A multiplex PCR has been developed for simultaneous Note: Jarisch-Herxheimer is a condition that results due to detection of common agents of genital ulcers such as a reaction to lipoproteins released by the death of Treponema Treponema pallidum, Haemophilus ducreyi, and herpes pallidum, during the antibiotic treatment to syphilis. simplex virus. Evaluation after Treatment Testing Algorithm Non-treponemal tests, such as VDRL and RPR are CDC recommends to use a testing algorithm comprising preferred over treponemal tests for monitoring response of non-treponemal test (as screening test), followed by to treatment. Antibody titers of treponemal tests remain 762 Section 10  Urogenital Tract Infections elevated even after clinical improvement. VDRL has to be Laboratory Diagnosis done at 3 months’ intervals for at least 1 year. ™™ Specimens: Exudate or swab from the edge of the ulcer ™™ For primary and secondary syphilis: following clinical and lymph node aspirate are the useful specimens improvement, there should be at least fourfold decline in ™™ Direct microscopy: H. ducreyi is a pleomorphic gram- the titer by the third or fourth month and non-reactive negative coccobacillus; occurs in groups or in parallel by 12 months chains ™™ For latent or late syphilis, or patients with multiple „„ They frequently take bipolar staining episodes of syphilis: It may show a gradual decline in „„ The arrangement has been described as school of titer, low titers may persist for years. fish or rail road track appearance. ™™ Culture: H. ducreyi requires factor X (hemin), but not Prevention factor V for its growth. Primary isolation is difficult. It Prevention of syphilis includes: can be grown on— ™™ Treatment of cases and contacts (sexual partners) „„ Rabbit blood agar or chocolate agar enriched with 1% ™™ Education about safe sex practices isovitalex and made selective by adding vancomycin ™™ Prophylactic use of barrier contraceptive methods. „„ It may also be grown on chorioallantoic membrane of the chick embryo. Chancroid (Haemophilus ducreyi) ™™ Optimum conditions required for isolation are 10% CO2, Haemophilus ducreyi is an etiologic agent of chancroid high humidity and incubation at 35°C for 2–8 days (or soft chancre), a sexually transmitted infection (STI) ™™ Colony morphology: Colonies are small, gray, https://t.me/docinmayking characterized by: translucent, 1–2 mm in size in 2–3 days ™™ Painful genital ulceration (Fig. 77.5) that bleeds easily; ™™ Biochemical reactions: H. ducreyi is biochemically inert. no inflammation of the surrounding skin Growth surrounding X disk can be used for presumptive ™™ Enlarged, tender inguinal lymph nodes (bubo). diagnosis Incubation period can range from 4–7 days. There is no ™™ Slide agglutination test: H. ducreyi is antigenically immunity following the infection; however, hypersensitivity homogeneous and cultures can be confirmed by may develop. agglutination with the antiserum ™™ A multiplex PCR assay has been developed for Epidemiology simultaneous detection of common agents of STIs Chancroid is a common cause of genital ulcers in including H. ducreyi (targeting 16S rRNA). developing countries. ™™ Transmission is predominantly heterosexual T Reatment Chancroid ™™ Male to female ratio is about 3:1 to 25:1 ‰‰ Drug of choice: Azithromycin (1g oral; single dose) ™™ Chancroid and HIV: Chancroid increases both the ‰‰ Alternative drugs: Ceftriaxone, ciprofloxacin or erythromycin efficiency of transmission and the degree of susceptibility ‰‰ Treatment of all the sexual partners is essential to HIV infection. Herpes genitalis Genital herpes is caused by herpes simplex viruses (HSV- 1 and 2). They produce widespread disease including cutaneous, mucocutaneous and systemic diseases (discussed in detail in Chapter 56). ™™ Genital ulcers: Characterized by multiple, painful, bilateral (widely spaced), tiny vesicular ulcers ™™ Inguinal lymphadenopathy: Enlarged, tender, firm, often bilateral ™™ Recurrent episodes are milder and recover faster than primary genital herpes. Recurrence is more common with HSV-2 than with HSV-1; the median number of recurrences is 4 and 1 week) Urethral discharge Purulent (flow of seed-resembling semen) Mucous to mucopurulent Complication DGI (polyarthritis and endocarditis) Reiter's syndrome: Characterized by conjunctivitis, urethritis, arthritis Water-can perineum and mucosal lesions Diagnosis Gram stain For Chlamydia—culture on McCoy and HeLa cell lines Culture on Thayer Martin media For Trichomonas—detection of trophozoite For Candida—detection of budding yeast cells in discharge For PCR—can be done for HSV or Chlamydia Treatment Ceftriaxone For Chlamydia—Doxycycline For Trichomonas—Metronidazole For Candida—Clotrimazole (as vaginal cream or tablet) Abbreviations: DGI, disseminated gonococcal infection; HSV, herpes simplex virus; PCR, polymerase chain reaction. Non-gonococcal urethritis (NGU) Chlamydiae are Bacteria, Not Viruses Chronic urethritis where gonococci cannot be demonstrat- Chlamydiae were once thought to be viruses because of ed has been labeled as non-gonococcal urethritis. NGU is possessing a few viral properties, such as: more common than gonococcal urethritis. Several agents ™™ They are obligate intracellular ™™ They cannot be grown in artificial media https://t.me/docinmayking are implicated in NGU such as: ™™ Bacteria: These agents are discussed below ™™ Filterable—small enough to pass through bacterial filters „„ Chlamydia trachomatis: Most common agent of NGU ™™ Produce intracytoplasmic inclusions. (has been discussed below) However, chlamydiae are now confirmed to be bacteria, „„ Urogenital Mycoplasma: Ureaplasma urealyticum because they have many other properties similar to that of and Mycoplasma hominis. bacteria, as follows: ™™ Viruses: Herpes simplex virus—genital herpes mainly ™™ Possess both DNA and RNA presents as genital ulcer (described earlier in this ™™ Their cell wall is similar to that of gram-negative bacteria chapter), but can also cause urethritis (although they lack peptidoglycan layer) ™™ Fungi: Candida albicans—in addition to urethritis, ™™ Multiply by binary fission it also causes vulvovaginitis, described later in this ™™ Susceptible to a wide range of antibacterial agents. chapter ™™ Parasites: Trichomonas vaginalis—in addition to Life Cycle urethritis, it also causes vulvovaginitis, described later Chlamydiae exist in two distinct morphological forms— in this chapter. elementary body (EB) and reticulate body (RB) (Fig. 77.8) Differences between gonococcal and non-gonococcal ™™ EBs are the extracellular and infective form; attach to urethritis are given in Table 77.3. the specific receptors on the host cells (e.g. squamous epithelial cells) Chlamydia trachomatis INFECTIONS ™™ EB→RB: Following entry, they transform into reticulate bodies; which are the intracellular form, survive inside Genus Description the cells by preventing phagosome-lysosome fusion Chlamydiae are obligate intracellular bacteria that ™™ RBs are replicative form; divide by binary fission. cause a spectrum of diseases in man such as trachoma, They are also the metabolically active form and can lymphogranuloma venereum (LGV), conjunctivitis, synthesize their own nucleic acid, lipids and proteins pneumonia and psittacosis and can also cause widespread except ATP; hence, they are called as energy parasites diseases in birds and mammals. (as they depend on host ATP for survival) ™™ RBs present inside the vacuole may enlarge to form Classification inclusion bodies, that can be readily detected by Based on genetic characteristics, family Chlamydiaceae histological stains has undergone recent taxonomic changes. Previously, ™™ RBs transform back to EBs, which are subsequently Chlamydia was the only genus under the family. But now, released from the host cells by 48 hours and then infect it comprises of two genera: other host cells 1. Chlamydia: It has one pathogenic species, C.trachomatis ™™ Sometimes, the development is arrested at the reticulate 2. Chlamydophila: It has two pathogenic species—C. body stage, leading to persistent infection; which plays psittaci and C. pneumoniae. They cause interstitial an important role in pathogenesis of ocular and chronic (atypical) pneumonia (discussed in Chapter 62). genital infections.  Chapter 77  Infective Syndromes of Genital Tract 767 Chlamydia trachomatis Infections Chlamydia trachomatis is primarily a human pathogen, causing ocular, urogenital and neonatal infections. Typing of Chlamydia trachomatis Biovars Historically, based on the disease produced, C. trachomatis was subdivided into two strains or biovars (Table 77.4). 1. TRIC (Trachoma-inclusion conjunctivitis) 2. Lymphogranuloma venereum (LGV) biovar. Serotypes and Disease Produced Based on antigenic structure of MOMP (and its gene ompA) of C. trachomatis, 18 serovars have been identified affecting humans. ™™ Serovars A, B, Ba and C are associated primarily with ocular disease called trachoma—a form of chronic keratoconjunctivitis (Chapter 78) ™™ Serovars D–K are associated with—(1) genital tract https://t.me/docinmayking infections (described below), (2) infant pneumonia Fig. 77.8: Life cycle of Chlamydia. (interstitial pneumonia, Chapter 62) and (3) ocular disease, called inclusion conjunctivitis, which is of two Antigenic Structure types (Chapter 78) Chlamydiae possess the following antigens: „„ Swimming pool conjunctivitis in adults ™™ G enus/group specific antigen: Chlamydial „„ Ophthalmia neonatorum in new born. lipopolysaccharide (LPS) is genus specific. It plays an ™™ Serovars L1–L3 causes a sexually transmitted infection, important role in the pathogenesis, acts by induction lymphogranuloma venereum (LGV). It is an ulcerative of TNF-α and other proinflammatory cytokines, which genital disease, described earlier this chapter. leads to scarring and fibrosis ™™ Species specific protein antigens: They are present at Genital Infections (C. trachomatis Serovars D–K) the envelope surface The genital infections produced by C. trachomatis serovars ™™ Serovar-specific antigens: They are the major outer D–K are as follows. membrane proteins (MOMP), encoded by ompA gene ™™ Nongonococcal urethritis (NGU): C. trachomatis is the ™™ Other antigens: Such as outer membrane complex most common cause of nongonococcal urethritis (NGU), proteins and heat shock proteins, which play important responsible for 30–50% of cases of NGU. It differs from role in pathogenesis. gonococcal urethritis (GU) by: Table 77.4: Features of Chlamydia infections. Species Character Biovar Serotype(s) Disease C. trachomatis Forms compact inclusions mixed with TRIC A, B, Ba, C Trachoma (Chapter 78) glycogen matrix D-K Genital chlamydiasis Sensitive to sulfonamide (D, Da, E, F, G, H, Inclusion conjunctivitis (Chapter 78) Natural human pathogen I, Ia, J, Ja, K) Infant pneumonia (Chapter 62) Leaves the host cell with a scar LGV L1, L2, L3 Lymphogranuloma venereum C. psittaci Forms diffuse vacuolated inclusions Nil Many serotypes Psittacosis (Atypical interstitial pneumonia) (Chapter 62) without glycogen matrix Transmission is by inhalation route—pet Resistant to sulfonamide birds (parrots) and poultry (turkeys and Natural pathogen of birds ducks) Leaves the host cell by lysis No man-to-man transmission C. pneumoniae Exclusive human pathogen Nil Only 1 serotype Community-acquired atypical pneumonia TWAR agent Forms inclusions without glycogen Associated with: atherosclerosis and asthma (Chapter 62) matrix Resistant to sulfonamide Abbreviations: TRIC, trachoma inclusion conjunctivitis; LGV, lymphogranuloma venereum; TWAR agent, Taiwan acute respiratory agent. 768 Section 10  Urogenital Tract Infections Onset of symptoms (incubation period is 7–10 days, „„ Contd... compared to 2–5 days for GU) L aboratory diagnosis Chlamydial infections „„ Symptoms: Mucopurulent discharge is followed by dysuria and urethral irritation (GU has purulent ‰‰ Nucleic acid amplification tests (NAAT), e.g. PCR ¾¾ The most sensitive and specific method discharge). ¾¾ Currently the diagnostic assay of choice. ™™ Postgonococcal urethritis (PGU): C. trachomatis is the ‰‰ Serology (antibody detection): most common cause of PGU. ¾¾ CFT or ELISA using group specific LPS antigen „„ Urethritis develops in men 2–3 weeks after recovery ¾¾ Micro-IF test detects antibody against species and serovar from GU specific MOMP antigen. „„ This occurs when patients with GU are treated with penicillin or cephalosporin alone without adding any Laboratory Diagnosis of Chlamydial Infections antichlamydial drugs (such as azithromycin). Laboratory diagnosis of various chlamydial infections is ™™ Epididymitis and proctitis: C. trachomatis is the most discussed here. common cause of epididymitis in males Specimen Collection ™™ Reactive arthritis (Reiter’s syndrome): It consists of conjunctivitis, urethritis (or, in females-cervicitis), It depends up on the types infection associated. arthritis, and characteristic mucocutaneous lesions ™™ Scrapings or swabs from infected sites: As chlamydiae „„ It occurs in 1–2% of cases of NGU, develops after1–4 are intracellular, the sample must contain cells. Hence, weeks after genital infection firm scraping or swabbing of the site is required. „„ Men are more frequently affected than women (10:1) Recommended specimens are: https://t.me/docinmayking „„ It is the most common cause of peripheral „„ Urethral swab for NGU inflammatory arthritis in young men „„ Endocervical swab for cervicitis „„ Knee, ankle, small joints of feet and sacroiliac joints „„ Conjunctival swabs for ocular infections-upper are commonly affected conjunctiva for trachoma and lower conjunctiva for „„ Most of the patients possess HLA-B27 haplotype ophthalmia neonatorum. „„ Mechanism: It is an immune-mediated inflam­ ™™ First catch urine samples in the morning contain greatest matory response to an infection at a distant site. C. amount of urethral secretions, hence it is the preferred trachomatis may act as a trigger organism to initiate specimen for urethritis or cervicitis an aberrant hyperreactive immune response that ™™ Nasopharyngeal aspirate and respiratory secretions for can produce inflammation of the targeted joints in suspected chlamydiae pneumonia genetically predisposed individuals ™™ Bubo aspirate for LGV. „„ Resolution usually occurs without specific treatment, Microscopy but relapse is common. ™™ In females: It produces various manifestations. ™™ Gram staining: Though, chlamydiae are gram-negative „„ Mucopurulent cervicitis is the most common they are poorly stained manifestation ™™ Presumptive diagnosis: Routine Gram staining often „„ It may progress to endometritis, salpingitis (fallopian reveals sterile pyuria (i.e. elevated neutrophils without any tube), PID (pelvic inflammatory disease) and finally organisms, including gonococci). In such a case any other pelvic peritonitis diagnostic test should be performed for confirmation „„ Perihepatitis (Fitz–Hugh–Curtis syndrome). ™™ Other stains: Such as Castaneda, Machiavello or Gimenez stains are better methods to detect chlamydiae L aboratory diagnosis Chlamydial infections from the samples. The inclusion bodies can be detected in the cytoplasm ‰‰ Specimen: Depends on the type of lesions ™™ Lugol’s iodine: The inclusion bodies of C.trachomatis can ‰‰ Microscopy: Detects chlamydial inclusion bodies be stained with Lugol’s iodine because of the presence ¾¾ Gram staining, Lugol’s iodine and other stains such as of glycogen matrix Castaneda, Machiavello or Gimenez stains ™™ Inclusion bodies: They are given various names such as: ¾¾ Direct IF: Used for direct detection of inclusion bodies. ‰‰ Antigen detection (LPS antigens): By enzyme immuno­ „„ Halberstaedter–Prowazek (H–P) body in trachoma assays „„ Miyagawa corpuscle in LGV ‰‰ Culture: It was the gold standard method in the past „„ LCL body (Levinthal-Cole-Lillie) body in psittacosis. ¾¾ Egg (yolk sac), mice inoculation and cell line culture ¾¾ Cell lines of choice- Direct Immunofluorescence Test (DIF)  McCoy, HeLa (for C. trachomatis) DIF is used as for direct detection of inclusion bodies in  HEp2 (for C. pneumoniae). clinical material, particularly from the genital tract and eye Contd... or can also be used for culture confirmation.  Chapter 77  Infective Syndromes of Genital Tract 769 Enzyme Immunoassays (Antigen Detection) Nucleic Acid Amplification Tests (NAAT) EIA detects chlamydial group specific antigens (LPS) from NAAT have revolutionized the diagnosis of chlamydial the samples by using specific monoclonal antibodies. infections. ™™ Advantages: NAAT is highly sensitive and specific, Culture takes less time, and detects even few copies of DNA Chlamydiae cannot be cultivated in artificial media. They from the sample. It can also differentiate the species can grow only in embryonated egg (yolk sac), animal (mice) and serovars and cell line. ™ ™ NAATs are currently the diagnostic assays of choice ™™ Both egg and mice inoculation methods are no longer for chlamydial infection as recommended by the in use CDC, replacing the so called gold standard culture ™™ Cell line culture was the traditional method of diag- methods nosis in the past, was considered as the gold standard ™™ Genes targeted are C. trachomatis specific genes such method as opacity protein gene or 16S or 23S rRNA „„ Though highly specific, it is less sensitive (90% ™™ Various methods available are: compared with NAATs), time consuming, technically „„ Polymerase chain reaction (PCR) demanding and labor intensive „„ Real time PCR „„ Choice of the cell line depends on the species: „„ FilmArray respiratory panel.  C. trachomatis: McCoy, HeLa are the recommended cell lines (Figs 77.9 and 77.10) Serology (Antibody Detection) https://t.me/docinmayking  C. pneumoniae can be isolated from Hep2 or Serological tests are useful for LGV, infant pneumonia and human fibroblast cell line psittacosis (systemic infections).  C. psittaci although grow well in cell culture, ™™ Complement fixation test (CFT) using LPS antigen was isolation should not be attempted in the routine used in the past; now obsolete laboratory because of the risk of laboratory ™™ ELISA based formats are also available using recombi- acquired infection. nant LPS antigen ™™ Promote contact: Pre-treatment of cell lines with ™™ Microimmunofluorescence (MIF) test: It uses the diethylaminoethanol (DEAE) dextran or centrifugation species and serovar specific MOMP (major outer after inoculation of specimen should be done to membrane protein) antigen (Fig. 77.11) promote contact between chlamydiae and the cells, thus „„ Serovar and species-specific antigens are spotted increasing the chance of isolation onto slides and incubated with serial dilutions of ™™ Incubation and growth detection: Cell lines are patient’s serum incubated in 10% CO2 for 48–72 hours, and growth is „„ After incubation and washing, antigen-antibody detected by the presence of inclusions under microscopy, complex is detected by fluorescein tagged antihuman after staining (Fig. 77.10). globulin. Fig. 77.9: HeLa cells infected with Chlamydia Fig. 77.10: Chlamydia trachomatis inclusion bodies (brown) in a trachomatis. McCoy cell culture. Source: Public Health Image Library, ID#/3847/Joe Miller/Centers for Disease Source: Public Health Image Library/ ID#: 3802, Dr E Arum; Dr N Jacobs, Control and Prevention (CDC), Atlanta (with permission). Centers for Disease Control and Prevention (CDC), Atlanta (with permission). 770 Section 10  Urogenital Tract Infections ™™ Non-gonococcal urethritis and epididymitis (mainly due to Ureaplasma and M. genitalium) ™™ Pyelonephritis (M. hominis), and urinary calculi (Ureaplasma) ™™ Pelvic inflammatory disease (mainly due to M. hominis) ™™ Postpartum and postabortal infection ™™ Non-urogenital infections (rare, due to M. hominis) such as: Brain abscess, wound infections or neonatal meningitis. Laboratory Diagnosis Culture and PCR are the appropriate methods for diagnosis of urogenital mycoplasmas. Ureaplasma forms very tiny colonies of 15–50 µm size, hence it was previously named Fig. 77.11: Anti-Chlamydia microimmunofluorescence test (MIF). as T-form Mycoplasma. Source: EUROIMMUN AG Pvt Ltd (with permission). T Reatment Urogenital Mycoplasma infections T Reatment C. trachomatis infections ‰‰ Macrolides (azithormycin) are the drug of choice for Ureaplasma and M. genitalium infections https://t.me/docinmayking ‰‰ For uncomplicated genital infection or trachoma or adult ‰‰ Doxycycline is the drug of choice for M. hominis conjunctivitis: ‰‰ However, resistance has been reported to both the drugs. ¾¾ Azithromycin is the drug of choice given as single dose of 1 gram tablet, per oral ¾¾ Alternatively doxycycline, tetracycline, erythromycin or Other Genital tract infections ofloxacin can be given for at least a duration of 7 days ¾¾ Both the sex partners should be treated COMMON TO BOTH THE SEXES ¾¾ Ceftriaxone should be added to the regimen as co-infec­ Apart from ulcerative genital disease and urethritis, the tion with gonococcus may be present in most of the cases. other genital tract infections common to both sexes include ‰‰ For complicated genital infection: Doxycycline (100 mg genital tuberculosis, and anorectal lesions. twice daily), or erythromycin (500 mg four times daily) are the drugs of choice, given for: ¾¾ 2 weeks for pelvic inflammatory disease and epididymitis Genital tuberculosis ¾¾ 3 weeks for LGV. Genital TB is diagnosed more commonly in female than in male patients. Prevention ™™ In female patients, it affects the fallopian tubes and Control measures for prevention of chlamydial genital the endometrium and can cause infertility, pelvic infections include: pain, menstrual abnormalities and adnexal swelling. ™™ Periodic screening of high-risk groups, such as young Endometrial biopsy shows tuberculous granulomas, women having multiple sex partners which can be sent for culture ™™ Treatment of both the sex partners ™™ In male patients, genital TB preferentially affects ™™ Use of barrier methods of contraception such as condoms the epididymis, producing a slightly tender mass that ™™ Abstain from sex till 7 days after starting the treatment. may drain externally through a fistulous tract. Other manifestations include orchitis and prostatitis. Urogenital mycoplasma INFECTIONS Mycoplasma (M. hominis, M. genitalium) and Ureaplasma Anorectal lesions (U. urealyticum and U. parvum) are associated with Anorectal lesions are frequently seen in—(1) women urogenital tract disease. and men who practice of anal-genital intercourse; (2) ™™ They frequently colonize female lower urogenital tract HIV-infected and other immunocompromised patients. such as vagina, periurethral area and cervix Common anorectal lesions include proctitis causing rectal ™™ Transmission: They are transmitted mostly by sexual ulcers, anal abscess and anogential warts contact or mother to fetus during birth. ™™ Proctitis (inflammation of the rectum): It can be caused by N. gonorrhoeae or C. trachomatis or HSV Clinical Manifestations „„ The common manifestations include itching, mu- The manifestations of urogenital mycoplasmas are as copurulent anal discharge, anal pain, bleeding, and follows: tenesmus (feeling of incomplete emptying of bowel)  Chapter 77  Infective Syndromes of Genital Tract 771 Vulvovaginitis Vulvovaginitis refers to inflammation of the vaginal mucosa (called vaginitis) and the external genitalia vulva (called vulvitis). It is the most common genital tract infection in females. ™™ Women present with vaginal symptoms such as abnormal discharge with/without offensive odor or itching ™™ The three most common causes of vaginitis in premenopausal women are trichomoniasis, bacterial vaginosis and vaginal candidiasis; can be differentiated from each other as given in Table 77.5. Trichomoniasis It is the most common parasitic sexually transmitted A B infection (STI), caused by a flagellated parasite Trichomonas Figs 77.12A and B: Condyloma acuminatum: A. Penis; B. Vagina. vaginalis. It has only trophozoite stage; there is no cyst Source: Public Health Image Library, A. ID# 3724; B. ID# 4097/Centers for stage. Trophozoite has two forms: Disease Control and Prevention (CDC), Atlanta (with permission). ™™ Flagellated trophozoite: It is the infective as well as the diagnostic form https://t.me/docinmayking „„Sigmoidoscopy reveals ulcerative lesions of the distal ™™ Amoeboid trophozoite: It is the actively replicating form, part of the rectal mucosa. found in the tissue feeding stage of the life cycle. ™™ Anogenital warts: Also called as condyloma acuminata is caused by human papilloma virus (HPV); the most Life Cycle common serotypes implicated being types 6 and 11. They Asymptomatic females are the reservoir of infection. have low malignant potential Humans acquire infection by sexual route. Flagellated „„ Site: They may be found in the genital area such as the trophozoites after entry, transform into amoeboid forms penile shaft, scrotum, or labia majora of the vagina or which multiply in the genital tract and cause infection. in the anal area (Figs 77.12A and B) They again transform back to flagellated trophozoites that „„ Appearance: They are generally pink in color and are discharged in vaginal/urethral secretions. project out from the surface of the skin. Size may vary; usually appear small, but can merge into large masses. Clinical Feature HPV is an oncogenic virus; causes carcinoma of cervix About 25–50% of individuals are asymptomatic, harboring and other sites (Chapter 80). the trophozoites and can transmit the infection; whereas ™™ In HIV-infected patients, anorectal lesions tend to others develop into disease after an incubation period of last longer, more severe, and are more difficult to treat 4–28 days. compared with infections in the immunocompetent ™™ Acute infection (vulvovaginitis): Adhesin proteins individuals help in attachment to the vaginal epithelium. Females ™™ Subclinical infection in HSV: Subclinical perianal shed- are commonly affected and present as vulvovaginitis, ding of herpes simplex virus (HSV) may occur in indi- characterized by thin profuse foul smelling purulent viduals without the history of rectal intercourse. This vaginal discharge. phenomenon is due to the establishment of latency in „„ Discharge may be frothy (10% of cases) and yellowish the sacral ganglia from prior genital tract infection, with green color mixed with pus cells subsequent subclinical reactivation in rectal epithelial „„ Strawberry appearance of vaginal mucosa (Colpitis cells macularis) is observed in 2% of patients. It is ™™ Unusual organisms: Rarely, anorectal lesions are characterized by small punctate hemorrhagic spots produced by enteric pathogens such as Campylobacter, on vaginal and cervical mucosa Shigella, and Entamoeba histolytica. „„ Other features include dysuria and lower abdominal pain „„ In males, the common features are nongonococcal Female genital tract disease urethritis and rarely epididymitis, prostatitis and Common infections of female genital tract include vul- penile ulcerations. vovaginitis, mucopurulent cervicitis, pelvic inflammatory ™™ Chronic infection: In chronic stage, the disease is mild disease, infections after gynecologic surgery and infections with pruritus and pain during coitus. Vaginal discharge associated with pregnancy. is scanty, mixed with mucus 772 Section 10  Urogenital Tract Infections Table 77.5: Differential diagnosis of vulvovaginitis. Feature Vulvovaginal Candidiasis Trichomonal Vaginitis Bacterial Vaginosis Etiology Candida albicans Trichomonas vaginalis Gardnerella vaginalis, various anaerobic bacteria Typical symptoms Vulvar itching and/or irritation Profuse purulent discharge; vulvar Malodorous, slightly increased itching discharge Discharge Scanty, white, thick and cheesy Profuse, white or yellow Moderate, thin, white to gray pH of vaginal fluid Usually ≤ 4.5 Usually ≥ 5 Usually >4.5 Fishy odor with 10% KOH None May be present Present Vaginal inflammation May be present Colpitis macularis (strawberry None (erythema) appearance) Microscopy of vaginal ↑ Leukocytes, epithelial ↑ Leukocytes; trophozoites seen in Clue cells, few leukocytes, no/few discharge cells; budding yeast cell with 80–90% of symptomatic patients lactobacilli pseudohyphae (Nugent’s score ≥7) Other laboratory findings Isolation of Candida spp. Antigen detection or PCR Culture, broad-range PCR Treatment of the patient Azole cream, tablet Metronidazole or tinidazole Metronidazole (tablet) and clindamycin cream Treatment of sexual None; topical treatment needed in Usually treatment needed None partner case of Candida dermatitis of penis https://t.me/docinmayking ™™ Complications: Rarely, it is associated with complications fluorescent stain and direct fluorescent antibody test like pyosalpinx, endometritis, infertility, low birth weight (DFA). DFA test is more sensitive (70–90%) than wet- and cervical erosions. It increases the risk of transmission mount examination (Figs 77.13 and 77.14). of HIV and HSV-2 infections. Trophozoite of Trichomonas vaginalis Laboratory Diagnosis It is pear shaped, measures 7–23 µm (Figs 77.13 and 77.14) Direct Microscopy ‰‰ It shows characteristic jerky or twitching motility in saline mount preparation Vaginal, urethral discharge, urine sediment and prostatic ‰‰ It bears five flagella—four anterior flagella and one lateral secretions can be examined. flagellum called as recurrent flagellum which traverses ™™ Wet (saline) mount of fresh samples (within 10–20 the parasite as an undulating membrane, that in turn is minutes of collection) should be done to demonstrate supported on to the surface of the parasite by a rod like the jerky motile trophozoites and pus cells (Fig. 77.13). structure called as costa Its sensitivity is variable (40–80%) and specificity is up ‰‰ It has a single nucleus containing central karyosome with to 100% evenly distributed nuclear chromatin and the cytoplasm ™™ Other staining methods include permanent stains contains a number of siderophore granule along the axostyle. (e.g. Giemsa and Papanicolaou stain), acridine orange Culture Culture is the gold standard method for diagnosis. It is highly sensitive 75–96% and specific (100%). Fig. 77.13: Trichomonas vaginalis trophozoite (Giemsa stain). Source: DPDx Image Library, Centers for Disease Control and prevention (CDC), Fig. 77.14: Trophozoite (flagellated) of Trichomonas vaginalis Atlanta (with permission). (schematic diagram).  Chapter 77  Infective Syndromes of Genital Tract 773 ™™ Specimen should be processed immediately into media ™™ Increase in the concentrations of: such as Lash’s cysteine hydrolysate serum media. Special „„ Gardnerella vaginalis: It is normally isolated from the container like “InPouch TV” can be used for sample female genital tract in low numbers; but in bacterial collection and culture vaginosis, it outnumbers other organisms ™™ Cultures should be incubated for 3–7 days, followed „„ Mobiluncus (motile, curved, gram-variable or gram- by mounting of the culture fluid to demonstrate the negative, anaerobic rods) trophozoites. „„ Several other anaerobes (Prevotella and some Peptostreptococcus) Antigen Detection in Vaginal Secretion „„ Mycoplasma hominis. Antigen detection methods are more sensitive than ™™ Decrease in the concentrations of lactobacilli microscopy, easy to perform and indicates recent infection. (lactobacilli maintain the acidic pH of the vagina, thereby Both rapid ICT and ELISA are available using monoclonal inhibiting the growth of pathogenic organisms). antibodies. Risk Factors Antibody Detection Bacterial vaginosis can occur in presence of the following ELISA is available using whole cell antigen preparation risk factors: and aqueous antigenic extract to detect antitrichomonal ™™ Coexisting other infections such as HIV, Chlamydia antibodies in serum and vaginal secretion of the patients. trachomatis, and Neisseria gonorrhoeae However, antibodies persist for longer time, hence cannot ™™ Recent unprotected vaginal intercourse differentiate between current infection and past infection. ™™ Vaginal douching https://t.me/docinmayking ™™ Premature rupture of membranes and preterm labor. Molecular Methods Molecular methods are highly sensitive, have replaced the Clinical Diagnosis culture techniques; target T. vaginalis specific genes such Bacterial vaginosis is so named because there is no as beta-tubulin gene. associated inflammation. It is clinically diagnosed by Other Supportive Tests Amsel’s criteria. ™™ Raised vaginal pH (>4.5): It is not specific as the vaginal Amsel’s Criteria pH is also raised in bacterial vaginosis. However, in Bacterial vaginosis is diagnosed if any 3 of the following 4 vaginal candidiasis, the pH is not raised findings are present: ™™ Positive whiff test: Fishy odor is accentuated when a 1. Slight to moderately increased thin (low viscous), white ho- drop of 10% KOH is added to vaginal discharge due to mogeneous vaginal discharge uniformly coated on vaginal production of amine wall „„ It is positive in more than 75% of cases 2. pH of vaginal discharge more than 4.5 „„ It is also positive in bacterial vaginosis. 3. Accentuation of distinct fishy odor (attributable to volatile amines such as trimethylamine) immediately ™™ Increased pus cells on wet mount examination is seen after vaginal secretions are mixed with 10% solution of in >75% of cases. KOH (Whiff test) 4. Clue cells: They are vaginal epithelial cells coated with T Reatment Trichomoniasis coccobacilli, which have a granular appearance and Metronidazole or tinidazole are the drug of choice. indistinct borders observed on a wet mount (Fig. 77.15). ‰‰ Standard therapy: 2 g, single dose is usually effective ‰‰ Both the sexual partners must be treated simultaneously to prevent reinfection, especially asymptomatic males Laboratory Diagnosis ‰‰ Resistance to metronidazole is rare, but reported (2.5-10%). ™™ Nugent’s score: It is a scoring system followed Consider repeating the treatment course, if the standard for the diagnosis of bacterial vaginosis; done by therapy fails (with 5 days therapy). counting the number of G. vaginalis, Mobiluncus and lactobacilli present in the Gram stained smear Prevention of vaginal discharge. A score of more than or equal Trichomoniasis can be prevented by: to 7 is diagnostic ™™ Treatment of both the sexual partners ™™ Culture: G. vaginalis requires enriched media such as ™™ Safe sex practices like use of condoms chocolate agar, BHI broth with serum, etc. ™™ Avoidance of sex with infected person. „„ It is gram-negative (appears gram-variable in smears), nonmotile, small pleomorphic rod, which Bacterial Vaginosis shows metachromatic granules Bacterial vaginosis affects women of reproductive age. This „„ It produces minute hemolytic colonies on blood condition is associated with an alteration of the normal agar, incubated aerobically under 5% CO2 for 24–48 vaginal flora, which is as follows: hours. 774 Section 10  Urogenital Tract Infections Other Genital tract infections in females Mucopurulent Cervicitis Mucopurulent cervicitis (MPC) refers to inflammation of the columnar epithelium of the endocervix. ™™ Agents: MPC is commonly caused by agents of urethritis such as C. trachomatis, N. gonorrhoeae, Mycoplasma genitalium ™™ Clinical diagnosis: The three cardinal signs of MPC are—(1) yellow mucopurulent discharge from cervix, (2) endocervical bleeding upon gentle swabbing, and (3) edematous cervical ectopy; the latter two findings are more common in chlamydial infection. HSV cervicitis produces ulcerative lesions of ectocervix ™™ Diagnosis: Yellow cervical mucus on a white swab removed from the endocervix suggestive of the presence of pus cells Fig. 77.15: Wet mount of vaginal secretion depicting clue cell. „„ Gram stain: The presence of ≥20 pus cells per oil immersion field within strands of cervical mucus https://t.me/docinmayking Source: Public Health Image Library/ID#: 14574/ M. Rein /Centers for Disease Control and Prevention (CDC), Atlanta (with permission). indicates endocervicitis „„ Intracellular gram-negative diplococci—may ™™ Identification from colonies is made either by indicates gonorrhea, but is sensitive only 50% cases conventional biochemical tests or by automated „„ PCR specific for N. gonorrhoeae or C. trachomatis is identification systems such as MALDI-TOF or VITEK ™™ Broad-range PCR amplification of 16S rRNA in vaginal more useful. ™™ Treatment: Comprises of ceftriaxone (single dose IM) fluid can be performed, with subsequent identification