VIVA QUESTIONS
A 26-year-old male attended the sexually transmitted infection (STI) out-patient department with the complaints of nonitchy skin lesions in the trunk and arms. He also had whitish skin lesions in the peri-anal region, suggestive of condylomata lata. With these findings, the working diagnosis was secondary syphilis. On routine investigations, venereal disease research laboratory (VDRL) and rapid card test for human immunodeficiency virus (HIV) were nonreactive.
WHAT IS YOUR INFERENCE OF VENEREAL DISEASE RESEARCH LABORATORY REACTIVITY?
Prozone phenomenon or false-negative venereal disease research laboratory
In secondary syphilis, all the serological tests including VDRL are 100% reactive. This nonreactive VDRL in the above scenario is due to the prozone phenomenon. VDRL is a simple, nontreponemal test used for screening syphilis. It is an antigen–antibody interaction resulting in an insoluble precipitate or agglutination, which are easily visualized and declared as reactive. The agglutination occurs only in the zone of equivalence, i.e. both antigen and antibody should be quantitatively equal. In secondary syphilis, due to the high bacterial load, the antibodies are produced in excess; hence, the agglutination does not occur resulting in a false-negative result. This state of antibody excess is known as “prozone phenomenon.” If we dilute the serum to bring back the zone of equivalence, the test will be reactive.
Studies document that the incidence of prozone phenomenon ranges from 0.2% to 2%. It is most often associated with secondary syphilis, HIV co-infection, and pregnancy. The prozone phenomenon is now attaining importance because of increasing prevalence of HIV. In HIV co-infection, abnormal B-cell behavior leads to excess antibody production resulting in prozone phenomenon.
WHAT ARE THE TYPES OF CHANCROID?
It is an acute genital ulcer sexually transmitted disease caused by Haemophilus ducreyi, it presents as multiple, painful ulcers in the genitalia with necrotic debris in the floor of the ulcer and the characteristic undermined edge. In addition, it is associated with either unilateral or bilateral inguinal bubo.
Following are the clinical types or variants of chancroid:
Dwarf chancroid: Single or multiple ulcers like herpes genitalis
Giant chancroid: Multiple ulcers coalesce to from a large, destructive ulcer
Transient chancroid: Ulcer heals within 6 days and followed by inguinal bubo as in lymphogranuloma venereum
Follicular chancroid: Occurs in the hair follicle apparatus with resemblance of folliculitis
Papular chancroid: Starts as a papule, then progress to form an ulcer. Later, the ulcer becomes raised particularly around the margin to mimic condylomata lata
Phagedenic chancroid: Widespread necrotic and deep ulcer with superinfection of Fusobacterium or Bacteroides
Serpiginous chancroid: Multiple ulcers to form a snake-like pattern
Pseudogranuloma inguinale: Beefy red ulcer, looks like donovanosis
Chancroidal ulcer: A single, large, tender, nonindurated ulcer with the absence of inguinal bubo, caused by organisms other than H. ducreyi
Mixed chancroid: Nonindurated tender ulcers of chancroid with an indurated nontender ulcer of syphilis.
IMPORTANCE OF TZANCK TEST IN SEXUALLY TRANSMITTED INFECTION
Tzanck test or Tzanck smear is scraping of an ulcer base to look for Tzanck cells. It is named after a French dermatologist, Arnault Tzanck. It is the simple, bed-side investigation to diagnose genital herpes in resource-poor settings.
The objective of Tzanck test is to identify Tzanck cells or multinucleated giant cells. The cells appeared to be inflated because of “ballooning degeneration.” The giant cells are either in tadpole or irregular teardrop shape, with multiple nuclei (many with eight or more).
Tzanck cells are found in:
Herpes simplex infections
Varicella and herpes zoster
Pemphigus vulgaris
Cytomegalovirus infections.
The procedure to do Tzanck test in genital herpes is as follows:
De-roof an early vesicle and scrape base with a sterile surgical blade
Smear onto a clean glass slide
Allow it to air dry or heat gently
Stain with Giemsa or Methylene blue or Wright's stain
Microscopic examination using oil immersion lens
Look for multinucleate giant cells.
Inference
Presence of multinucleated giant cells is suggestive of genital herpes.
Limitation of Tzanck test in diagnosing genital herpes:
It does not differentiate between herpes simplex virus (HSV) 1 and 2.
DESCRIBE “DONOVAN BODIES”
These are intracellular inclusions of the rod-shaped, oval organisms (Klebsiella granulomatis) seen in the cytoplasm of mononuclear phagocytes or histiocytes in tissue samples from patients with granuloma inguinale. Sometimes, they may also have bipolar inclusions resembling a safety pin. They appear deep purple when stained with Wright's stain. Other stains used are Leishman, hematoxylin and eosin, and pinacyanole.
They were discovered by Major Charles Donovan who also discovered Leishmania donovani as the causative agent of visceral leishmaniasis. In 1905, he was a Professor at Madras Medical College, when he first demonstrated “Donovan bodies” in the oral ulcerative lesions of a ward boy.
Demonstration of the donovan bodies in the tissue smear
The tissue from the edge of the ulcer is grabbed by using an artery forceps. Then, it is crushed between two slides and stained by Giemsa or Leishman. Microscopic examination shows the classical Donovan bodies. It is the gold standard method of diagnosing donovanosis, as till now, we do not have any reliable serological or culture tests.
WHAT ARE THE REASONS FOR VENEREOPHOBIA IN MALE?
(1) Spermatorrhea: This is reported as a urethral discharge and had invariably followed defecation. We have to convince the patient that is merely a normal secretion from the glands. (2) Sticky meatus: This is found in patients because of vigorous “milking” of the penis. With the negative Gram-stain, the patient has to be reassured by the explanation that the discharge is the normal product from glands within the penis by his own milking. (3) Threads in the urine: The phobic patient examines his urine carefully and discovers threads as if he has gonococcal or nongonococcal urethritis. It ought to be explained to the patient that these are due to a change in the character of the lining of the penis brought about by the past infection and did not indicate any present infection. (4) Phosphaturia: This is reported by the patient as a discharge after micturition. A sudden milkiness appearing in the stream toward the end of the act of micturition is interpreted by the patient as a discharge. We can reassure the patient by watching its disappearance on the addition of acetic acid. (5) Presence of smegma: Gentle washing with water makes it disappear and counsel the patient to maintain personal hygiene. (6) Pearly penile papule: Soon after a sexual activity, patient has a close watch on the penis and gets afraid of this anatomical variant as wart or molluscum contagiosum. We could explain the patient that is seen in around 20% of the individuals.
DESCRIBE PENICILLIN ALLERGY
A β-lactum antibiotic, commonly used in STI to treat the syphilis, has all the four types of hypersensitive reactions of Gell and Coombs. Both natural and semisynthetic penicillins could cause allergy, but it is more commonly seen after parenteral than oral administration. Penicillin G is the most common type implicated in drug allergy. The penicillin hypersensitivity is unpredictable, i.e. an individual who tolerated penicillin earlier may show allergy on subsequent administration. The incidence of penicillin reactions is from 0.7% to 10%, but the incidence of anaphylactic reactions is just 0.004–0.015%. Rarely, cross-reactive allergic reactions to cephalosporins are also seen in penicillin-allergic patients.
Benzylpenicilloyl polylysine injection is the only Food and Drug Administration-approved skin test to find out the penicillin allergy. It is a skin test antigen reagent that reacts specifically with benzylpenicilloyl IgE antibodies triggering the release of inflammatory mediators which produce an immediate wheal and flare reaction at a skin test site. The benzylpenicilloyl is a hapten and it is the major antigenic determinant in penicillin-allergic individuals. Nonbenzylpenicilloyl haptens are minor determinants, as it rarely provokes an immune response in penicillin-treated individuals.
This test is indicated for the assessment of sensitization to penicillin (mainly to benzyl penicillin or penicillin G) in patients suspected to have clinical penicillin hypersensitivity. The incidence could be more than 50% in a history-positive patient with a positive skin test, whereas negative skin test is associated with an incidence of immediate allergic reactions of < 5% after the administration of therapeutic penicillin.
The interpretation of intradermal test
Inject an amount of the test solution to raise a small intradermal bleb of about 3 mm in diameter, and with a separate syringe and needle, inject a little amount of saline 5 cm away from the test site as a control. Most skin reactions will develop within 5–15 min and response to the skin test is read at 20 min as follows:
Positive response - itching and significant increase in size of original blebs to at least 5 mm. Wheal may exceed 20 mm in diameter.
Negative response - no increase in the size of original bleb and no greater reaction than the control site.
Ambiguous response - wheal only slightly larger than initial injection bleb, with or without accompanying erythematous flare and slightly larger than the control site.
DESCRIBE THE MECHANISM OF ACTION OF ACICLOVIR
It is an antiviral drug used to treat genital herpes (HSV). It is a prodrug. It has to be metabolized to its active form for its anti-viral activity.
The mechanism of acyclovir is depicted in the [Flow Chart 1].
Flow Chart 1.
Mechanism of action of acyclovir
When HSV is co-infected with HIV, mutation of viral thymidine kinase is more frequent, leading to acyclovir resistance.
WHAT IS IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME?
The objective of antiretroviral therapy (ART) in immunocompromised HIV-infected individuals is immune reconstitution. However, an adverse manifestation of this effect may sometimes occur. Immune reconstitution inflammatory syndrome (IRIS), also known as immune restoration disease, refers to a disease- or microbial-driven inflammatory response in HIV-infected patients that may be observed after an initiation of ART or shift to more active ART.
IRIS is accompanied by an increase in CD4 cell count and a rapid decrease in viral load. IRIS can occur at any CD4 count. It occurs within the first 4–8 weeks after the initiation of ART.
Following the immune re-constitution, inflammatory reactions to many pathogens including mycobacterium, fungi, virus, and bacteria do occur. IRIS also involves the worsening of malignancies such as Kaposi's sarcoma. Symptomatic treatment and supportive care for patients with IRIS is needed. In severe cases, prednisolone 1–2 mg/kg has to be given for 1–2 weeks. Except in severe cases, ART should not be stopped in patients with IRIS.
ENUMERATE THE RAPID CARD TEST FOR HUMAN IMMUNODEFICIENCY VIRUS
Early and accurate diagnosis of HIV infection is essential for timely identification of patients needing ART and for instituting HIV-prevention strategies. In India, the voluntary counseling and testing facilities are employing strategy/algorithm III for the diagnosis of HIV infection as per the guidelines laid by the National Acquired Immunodeficiency Syndrome Control Organization. The primary methodology for HIV testing has shifted from enzyme-linked immunosorbent assay to rapid diagnostic tests in recent years, especially in resource-limited settings. The HIV antigen-colloidal gold conjugate embedded in the sample pad reacts with the HIV-antibody present in serum or plasma sample forming conjugate/HIV antibody complex. As the mixture is allowed to migrate along the test strip, the conjugate/HIV antibody complex is captured by a second antibody immobilized on the membrane forming a colored test band in the test region.
Serum or plasma may be used in this test. The test starts with a sample applied to the sample well and add, provided sample diluents immediately. For test cards: One drop (10 µl) of serum or plasma is dropped onto the “S” well of the test card using the plastic dropper provided. Then, two drops of sample diluents are added immediately to the “D” well after the specimen is added. Results may be interpreted at 15 min.
Positive: Both purplish red test band and purplish red control band appear on the membrane. If the antibody concentration is lower, the test band is weaker
Negative: Only the purplish red control band appears on the membrane. The absence of a test band indicates a negative result
Invalid: There should always be a purplish red control band in the control region regardless of test result. If control band is not seen, the test is considered invalid.
All positives must be confirmed using Western blot technique. Few studies revealed that the sensitivity and specificity of the rapid card test were 77.5% and 99.3%, respectively.
WHAT ARE THE INDICATIONS OF TABLET AZITHROMYCIN IN SEXUALLY TRANSMITTED INFECTION?
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Conflicts of interest
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