Frans Radebe. National Institute of Communicable Diseases
A 29-year ago man presented at a dedicated sexually transmitted infections (STI) clinic in Johannesburg complaining of genital sores that started as small blisters on the penis that started spontaneously three weeks previously. He had the same sores in the past, which healed without treatment. He was seen by a private GP and treated with fluconazole, doxycycline and ceftriaxone but the symptoms persisted. On clinical examination he had septic ulceration of the glans penis with tenderness on palpitation without any discharge.
The patient was HIV positive with CD4 T cell count of 306 cells/mm3. He was ART-naive. He was treated syndromically according to genital ulcer treatment algorithms with benzathine penicillin IM, 2.4 MU, oral erythromycin 500mg 6 hourly for 7 days, and oral acyclovir 400mg 8 hourly for 7 days.
Samples were collected from the patient following the collection of brief demographic data and consent. These included a genital swab from the ulcer for multiplex PCR, and a blood sample for syphilis serology (RPR and TPPA).
The M-PCR for genital ulceration picks up HSV-1 and -2, Treponema pallidum, Haemophilus ducreyi, and Chlamydia trachomatis serovars L1-3. The patient was positive for HSV-2, TPPA was positive at a titre of 1:80, and RPR negative.
Question 1: What is the natural history, pathogenesis and clinical features of herpes virus infections?
Answer to Q1
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Oral herpes, the visible symptoms called cold sores or fever blisters, and genital herpes are the common clinical manifestations of HSV infection. The virus cycle is between periods of active disease, presenting as blisters containing infectious virus particles with an incubation period of 2-21 days, followed by a remission period. Genital herpes is often asymptomatic, though viral shedding may still occur.
After initial infection, the viruses are transported along sensory nerves to sensory nerve cell bodies, where they become latent and reside lifelong. Outbreaks become less severe after several years and become more sporadic with perpetual asymptomatic carriage but still may be contagious to others. There are many causes of recurrence and potential triggers including immunosuppressant drugs. Herpes is contracted through direct contact with an active lesion or body fluid of an infected person. Transmission may occur through skin-to-skin contact during periods of asymptomatic shedding. Barrier protection methods are most reliable method of preventing transmission by reducing risk rather than eliminating it. Antibodies that develop following an initial infection with a type of HSV prevents re-infection with the same virus type.
Herpes is identified by clinical examination of persons with no previous history of lesions and contact with an individual with known HSV infection. Genital herpes can be more difficult to diagnose since most HSV-2 infected persons have no classical symptoms (or there are no ulcers on physical examination) and can be confused with fungal infection and atopic dermatitis. The majority of genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs. These asymptomatic viral shedding can occur regardless of symptomatic outbreaks frequency and how long diagnosed4.
There is a syndemic relationship between genital herpes and HIV, which affects both patients at risk of acquiring HIV, and HIV-infected patients. Genital herpes is helping to fuel the HIV epidemic by increasing risk of HIV acquisition and transmission. It provides a portal of entry for HIV by increasing the number of CD4+ and CD8+ cells in genital mucosa and skin, and by increasing the replication of HIV due to HSV-2 reactivation and/or shedding thus increasing the level of HIV in plasma and genital tract1. Herpes, like other STIs, facilitate HIV transmission by disruption of epithelial mucosa barriers, increase the number of HIV target cells in the genital tract, increase expression of HIV co-receptors, induce secretion of cytokines (increase HIV shedding) and HIV alters natural history of some STIs2.
Question 2: Discuss the laboratory diagnostic tests available for genital herpes.
Answer to Q2
The following are available standard and rapid diagnostic tests for HSV:
Patients seeking treatment or screening for a particular STI should be evaluated for all common STIs. Laboratory testing which are highly sensitive and specific for diagnosis, are often used to confirm a diagnosis of genital herpes, which include culture, direct fluorescent antibody, skin biopsy and PCR to test for the presence of viral DNA.
The diagnostic methods must be tailored to clinical presentation, either symptomatic or asymptomatic and the clinical diagnosis must be confirmed by a laboratory test since the clinical diagnosis of genital herpes is often insensitive and nonspecific especially in patients co-infected with HIV.
Serological testing for antibodies to HSV is not useful for diagnosis in clinical practice. The IgM assay could not differentiate between antibodies to HSV-1 or HSV-2 infection. However, the new Immunodot glycoprotein G-specific (IgG) HSV test is more specific at discriminating HSV-1 from HSV-2 and is 80-98% sensitivity3. HSV serologic testing should be included in a comprehensive evaluation for STIs among persons with multiple sex partners, HIV infected and among MSM at increased risk for HIV acquisition.
Question 3: How would you treat the condition?
Answer to Q3
Herpes simplex virus infects the body for life and cannot be eradicated. However, there are several treatments than can be used to reduce the severity of outbreaks and to speed up the healing period. They reduce pain and the number of blisters and sores that are present during the initial outbreak. They are available in oral, intravenous, and topical varieties. In most countries, the patients presenting genital ulcer syndrome are managed as per this patient5. Aciclovir or equivalent is the treatment of choice for herpes virus infection.
The non-therapeutic part of the treatment package should include:
The patient was reassured that acyclovir would better the condition and he needed to come back for review in a week. It was also emphasized the condition required him to abstain from sexual intercourse until the lesions had completely healed, and that recurrence may occur. He was encouraged to enroll into an ART programme. Consent was obtained from the patient to use the picture for educational purposes.
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