Herpex Simplex Virus
Herpes Simplex virus is a double stranded DNA virus belonging to the Herpesviridae family. The subfamily, Alphaherpesviruses to which herpes simplex belongs, contains three types of viruses?: types 1, 2 and 3. All three types have an affinity for neurons which act as the site of latent infection. Types 1 and 2 are known as Human Herpes virus type 1 (Herpes Simplex virus 1) and Human Herpes virus type 2 (Herpes Simplex virus 1). Type 3 is the varicella zoster virus. The herpes virus occurs naturally in humans. No animal reservoirs are present. The reservoir is maintained by individuals who have latent infection. Latent infection due to persistence of the virus in the nerve root ganglia and periodic reactivation are characteristic features of the Herpes virus family.
HSV1 frequently causes lesions in and around the oral cavity. These are called ?fever blisters?. The virus is present in large quantities in these vesicles. The incubation period is approximately 14 days after which the blisters appear with systemic features such as fever. They remain for a week or more after which they undergo complete healing. However, the virus undergoes a period of latency buried in the surrounding nerve ganglia wating for reactivation in the future. The disease is particularly fulminant in immunocompromised patients such as the following:
- those on chemotherapy
- transplant patients
- patients with uncontrolled diabetes
- AIDS patients
Severe cases involving the eye and leading to blindness have also been reported. HSV1 has the capablity of causing encephalitis and genital lesions.
Infection with HSV2 is a rampant sexually transmitted disease. According to the World Health Organization (WHO), in the United States alone, 40 to 60 million people are infected with HSV2 with an incidence of 1 to 2 million infections and 6 to 8 lac clinical cases per year. The prevalence in the 30 to 40 year old population is approximately 30%. The incidence in developing countries is variable and ranges between 2% to 74%. This enormous difference is primarily related to underreporting of clinical cases in these regions. The percentage of transmission of infection is greater from male to female than female to male due to exposure of more mucosal surface area in females. Therefore, the prevalence of disease is greater among women.
The primary presentation of HSV2 infection is characterized by fluid filled vesicles in and around the anus, vulva and penis. When the vesicles rupture, small, shallow, red painful ulcers remain. Healing takes approximately two to three weeks. Healing time is especially prlonged in immunocompromised patients. The virus remains latent in the sacral root ganglia. Periodic reactivations of genital herpes which occur thereafter are typically mild and may number 4 to 5 outbreaks annually. The WHO estimates that only about 13% to 37% of individuals with HSV2 infection are symptomatic. The majority of infections is sub-clinical and may not be noticed by the individual due to the mild, self limiting features of the disease. But it is important to note that individuals with sub-clinical infection shed the virus and are capable of infecting their sexual partners. Once HVS2 infection is diagnosed in an individual, counseling is critical and the partner must be examined for symptoms of infection and, if necessary, receive appropriate treatment. This method of ?contact tracing? is extremely important from the public health point of view for all sexually transmitted diseases.
HSV2 is a critical risk factor in the spread of HIV. The number of individuals with symptomatic HSV2 infection is greater in those who are HIV infected than those who are HIV negative. These patients frequently contract severe disease which has an extended healing time due to their immunocompromised status. HSV2 can also be transmitted by an infected mother to her newborn via genital secretions. This is highly prevalent if active disease is present during delivery. HSV2 affects the newborn by causing severe systemic infection with encephalitis and high mortality rate. Therefore, in mothers who are positive for HSV2 infection with active outbreak, the newborn is delivered by a caesarian section and receives antiviral prophylaxis. The risk of neonatal herpes is only about 3% in the developed world but very little data exists on this issue from the developing countries in which it is likely to be much higher.
The role of antiviral agents in the treatment of herpes is not to cure the infection, but rather to assist in reducing the duration of clinical illness thereby reducing potential for infection. Acyclovir administered at dosages of 200 mg five times per day was the drug utilized for herpes therapy in the earlier days, but over the years the virus has developed resistance to acyclovir. Newer drugs such as valacylcovir prescribed at 500mg twice a day for a period of 3 days and famciclovir 125 mg twice a day administered for 5 days are the current treatments of choice. Recently, a one day regimen of 1000mg famciclovir given twice a day has demonstrated positive results in patients with either prodromal symptoms of herpes or lesions of genital herpes. Other agents are also available for topical use such as 15% idoxuridine with dimethyl sulfoxide (DMSO), edoxuridine and penciclovir. Studies have shown synergistic activity to exist between interferon alpha and agents such as caffeine, trifluorothymidine, dimethyl sulfoxide, nonoxynol-9 and even ascorbic acid.
Diagnosis of herpes viral infections is primarily based on antibody detection which confirms past infection. Western blot assays can be used to differentiate between the types of virus causing the infection. Cell cultures and molecular methods can also be used to confirm the diagnosis.
Since herpes simplex infection cannot be cured, the role of prophylactic vaccination becomes crucial. A suitable vaccine which would protect people from the infection has not yet been produced. The majority of candidates for the vaccine have been the envelope glycoproteins such as gB2 or gD2 administered alone or in combination. Animal studies have been conducted with deactivated virus vaccine but not found to be effective and therefore were discontinued. A potential live attenuated HSV2 vaccine prepared by Xenova /GSK has been tested in Phase II trials as a therapeutic vaccine. Though this vaccine was well tolerated and presented positive neutralizing antibodies, it did not affect the frequency of recurrence or the shedding of the virus in symptomatic patients. This vaccine is being refocused as a prophylactic vaccine rather than a therapeutic vaccine.
