Combination prevention: new hope for stopping the epidemic.

HIV research has identified approaches that can be combined to be more effective in transmission reduction than any 1 modality alone: delayed adolescent sexual debut, mutual monogamy or sexual partner reduction, correct and consistent condom use, pre-exposure prophylaxis with oral antiretroviral drugs or vaginal microbicides, voluntary medical male circumcision, antiretroviral therapy (ART) for prevention (including prevention of mother to child HIV transmission [PMTCT]), treatment of sexually transmitted infections, use of clean needles for all injections, blood screening prior to donation, a future HIV prime/boost vaccine, and the female condom. The extent to which evidence-based modalities can be combined to prevent substantial HIV transmission is largely unknown, but combination approaches that are truly implementable in field conditions are likely to be far more effective than single interventions alone. Analogous to PMTCT, "treatment as prevention" for adult-to-adult transmission reduction includes expanded HIV testing, linkage to care, antiretroviral coverage, retention in care, adherence to therapy, and management of key co-morbidities such as depression and substance use. With successful viral suppression, persons with HIV are far less infectious to others, as we see in the fields of sexually transmitted infection control and mycobacterial disease control (tuberculosis and leprosy). Combination approaches are complex, may involve high program costs, and require substantial global commitments. We present a rationale for such investments and cite an ongoing research agenda that seeks to determine how feasible and cost-effective a combination prevention approach would be in a variety of epidemic contexts, notably that in a sub-Saharan Africa.

Newer trends in the management of genital herpes.

Management of genital herpes is complex. Apart from using the standard antivirals, an ideal management protocol also needs to address various aspects of the disease, including the psychological morbidity. Oral acyclovir, valacyclovir or famciclovir are recommended for routine use. Long-term suppressive therapy is effective in reducing the number of recurrences and the risk of transmission to others. Severe or disseminated disease may require intravenous therapy. Resistant cases are managed with foscarnet or cidofovir. Genital herpes in human immunodeficiency virus-infected individuals usually needs a longer duration of antiviral therapy along with continuation of highly active anti retroviral therapy (HAART). Genital herpes in late pregnancy increases the risk of neonatal herpes. Antiviral therapy and/or cesarean delivery are indicated depending on the clinical circumstance. Acyclovir appears to be safe in pregnancy. But, there is limited data regarding the use of valacyclovir and famciclovir in pregnancy. Neonatal herpes requires a higher dose of acyclovir given intravenously for a longer duration. Management of the sex partner, counseling and prevention advice are equally important in appropriate management of genital herpes. Vaccines till date have been marginally effective. Helicase-primase inhibitors, needle-free mucosal vaccine and a new microbicide product named VivaGel may become promising treatment options in the future.

An historical and clinical review of the interaction of leprosy and pregnancy: a cycle to be broken.

Since earliest history the person with leprosy has been shut out from society. Laws have prohibited marriage and allowed divorce of those with leprosy. Segregation of the sufferer from the rest of society has been followed by separation of the sexes, and of leprous parents from their children. With the advent of antileprotic drugs, first dapsone then multidrug therapy (MDT), infection can be treated, individuals made non-infectious, and the pool of infection in the community reduced. The clinical signs of leprosy are due not to the degree of infection but to the immunological status of the host. Hormonal changes at puberty and in pregnancy can cause variation of the host's immune status. Pregnancy in women with leprosy is a hazardous undertaking. First appearance of leprosy, reactivation of the disease and relapse in 'cured' patients is likely to occur particularly in the third trimester of pregnancy. Leprosy reactions caused by variation in cell mediated and humoral immunity are triggered off by pregnancy: type 1 reaction (reversal reaction, RR) occurs post partum, while type 2 reaction (erythema nodosum leprosum, ENL) peaks in late pregnancy. Both types of reaction continue long into lactation. Neuritis with loss of both sensory and motor function is associated with relapse and reaction. Relapse, reaction and nerve damage, especially 'silent neuritis', with subsequent deformity and disability, occur not only in women on apparently effective treatment but also in those who have received MDT and have been released from treatment (RFT). To prevent disability, research is urgently needed into the mechanisms of early and late reaction and neuritis. Pregnancy is not only a trigger factor for reaction but an ideal in vivo model for research. Up to 20% of children born to mothers with leprosy may develop leprosy by puberty. While early leprosy in young children is self-healing, when marriage and childbearing take place at an early age the daughters of mothers with leprosy are likely to run the risk of experiencing the adverse effects of pregnancy on leprosy. Increased awareness and health education, as well as long term surveillance of 'cured' leprosy patients, are essential to break a potentially vicious cycle of leprosy and pregnancy. Women with cured leprosy could play an important role in screening for and detection of both early leprosy in children and late, post-MDT RFT, nerve damage in their mothers.