A BRIEF INTRODUCTION
Infection with the Herpes simplex virus (HSV) is a massive worldwide health issue. Currently, more than 3.7 billion people under the age of 50 are infected with HSV-1, and 417 million people between 17 and 49 years of age suffer from HSV-2 infection.  In most studies, the seroprevalence of HSV-1 in adults is between 80 and 90 percent, while HSV-2 seroprevalence is 10 to 25 percent. 
CHARACTERISTICS OF HSV
"According to the Centres for Disease Control and Prevention (CDC), 776,000 persons in the United States get new genital herpes infections each year"
HSV-1 infection is restricted to the oropharynx, and the virus is spread by respiratory droplets or saliva, with kissing being the most common method of transmission. Symptoms of HSV-1 infection range from completely asymptomatic to a fever, throat ulcers, vesicular lesions and gingivostomatitis. 
HSV-2 is mostly spread through sexual contact.  Genital herpes is distinguished by inflammatory vesicles in the penis or cervix, vulva, vagina, or perineum; or tender inguinal lymphadenopathy. The infection may also present as mild or even asymptomatic, making its transmission easy.  According to the Centres for Disease Control and Prevention (CDC), 776,000 persons in the United States get new genital herpes infections each year. 
HSV has biological characteristics specific to it, such as latency and reactivation. Subsequent outbreaks, caused by a reactivation of latent virus results in symptomatic recurrence of lesions or asymptomatic viral shedding . Therefore, it is imperative that clinicians spend enough time educating patients and their partners about disease prevention and management.
RISK FACTORS FOR HSV
"A cross-sectional study demonstrated the accumulation of resistance mutations to anti-retroviral drugs in HSV-2 seropositive patients, thus establishing a link between genital herpes and HIV disease progression"
A history of a prior sexually transmitted disease (STD), early age of first sexual intercourse, female gender, black race, multiple abortions, high number of sexual partners, patterns of sexual activity, hormonal contraception, and low socioeconomic status or level of education are some of the risk factors for HSV infection.  A positive correlation between usage of tobacco products, alcohol and HSV-2 infection was established by a study conducted by Beydoun et al. in 2010 in the USA.  The study also demonstrated a consistent increase in genital herpes infection for those who initiated sexual activity prior to 13 years of age. 
Globalisation of the sex industry has made HSV-2 a potential global burden.  A study conducted by Khan et al. has proven incarceration to be contributing to STDs by disrupting sexual networks, resulting in higher levels of sexual interchanges between high and low risk persons, hence causing more STD-discordant partnerships.  Prostitutes, men who have sex with men (MSM) and refugees are some of the vulnerable populations. Neonatal HSV infection, which has a 65% mortality rate and 80% rate of long-term disability even with antiviral therapy is caused by primary infection during the third trimester of pregnancy. 
A cross-sectional study in 2020 demonstrated the accumulation of resistance mutations to anti-retroviral drugs in HSV-2 seropositive patients, thus establishing a link between genital herpes and HIV disease progression.  There has been an evolving synergy between the transmission and prevention of HSV-2 and HIV infection. Therefore, it is crucial to identify communities of high sero-prevalence of HSV-2, as they might operate as a reservoir for future HIV infections. Various epidemiological studies have also associated HSV-2 infection with cervical cancer, making genital herpes an intriguing research subject over the years. 
RISK FACTOR REDUCTION
"Since antiviral drugs fail to stop viral shedding and transmission, an effective vaccine is the need of the hour"
The high prevalence of HSV infection must be addressed by public health authorities through a comprehensive preventive effort, as it has no effective vaccination. Socio-demographic and behavioural risk factors should be utilised to target certain sub-populations with health education and screening interventions.
Additional interventions such as HIV screening, HIV therapy for HSV-2/HIV co-infected individuals, and avoiding new-born contact with active HSV lesions should be carried out. Caesarean section continues to be the gold standard in pregnant women with active genital lesions.  Health education should include counselling, partner disclosure, abstinence during genital lesions, condom use and psycho-sociological risk-reduction. 
In heterosexual, HSV-2–discordant couples, once-daily suppressive medication with valacyclovir has shown to dramatically lower the probability of genital herpes transmission.  But since antiviral drugs fail to stop viral shedding and transmission, an effective vaccine is the need of the hour.
VACCINATION IN HSV
Two prophylactic vaccines (HerpeVac, GSK), both targeting the prevention of genital herpes have been studied for effectiveness and safety in large phase III clinical studies in the recent years. Both vaccines induced high serum titres of HSV neutralizing antibody, but both vaccines failed in clinical trials as the antibody levels waned in few months. Also, during these trials, mainly systemic immunity was seen, even though HSV-2 being a local infection requires a robust immune response at the mucosal level. 
The Disabled Infectious Single Cycle (DISC) vaccine was a recent therapeutic vaccination to complete a phase III clinical study, but despite being safe to use, the vaccine did not reach its clinical goals. 
Similarly, there have been various attempts to produce an effective vaccine to manage genital herpes, but none have been successful. HSV-2 being a life-long sexually transmitted infection with no absolute cure, needs to be brought into the attention of future researchers, as an effective vaccine would be a significant step forward in improving global sexual and reproductive health.
Author: Dr. Tejaswini Ashok
Editor: Ms. Vibha Hegde