Novel and Emerging Treatments
Cimetidine (Tagamet®) is a medication commonly used for treating acid reflux (GERD). It inhibits the production of stomach acid by blocking the signaling pathway for histamine (Hsu 1991). Histamine signaling modulates the immune response to some viruses as well, and researchers have shown that oral administration of cimetidine significantly accelerates the healing of skin lesions and provides pain relief in adults with shingles (Miller 1989). Supporting this finding, an in vitro study performed on cells from 22 people with shingles found that cimetidine improves the body’s immune response, and suggested that healing from skin rash and pain could be accomplished significantly faster (Komlos 1994). Findings from another study, which enrolled 221 patients with shingles, suggested cimetidine may even be efficacious when used during the prodromal period, before manifestation of the characteristic rash (Kapińska-Mrowiecka 1996).
In addition, numerous case studies have been published demonstrating that cimetidine may reduce the severity and duration of symptoms of both shingles and herpes outbreaks (van der Spuy 1980; Mavlight 1984; Hayne 1983). For example, one study made the observation that a patient who developed shingles just before starting a course of cimetidine for gastric ulcer experienced a significant relief of shingles symptoms. Based on this finding, which was unexpected at the time, the researchers prescribed cimetidine to several other patients with shingles and oral herpes, and the vast majority of them experienced relief of their symptoms. Another exciting finding was that in one patient with herpetic keratitis, the attacks occurred less frequently and were shorter in duration following cimetidine administration (van der Spuy 1980).
Topical Antimicrobial Agents
An emerging therapy for infections caused by viruses in the Herpesviridae family is the use of topical microbicides, which are compounds that have antiviral properties. One of the biggest challenges in the field of genital herpes research is to find ways to prevent viral transmission, and this is particularly important because the sexual spread of the virus often occurs during periods when patients have no visible lesions, a phenomenon called “asymptomatic shedding” (Keller 2005).
As a result, compounds that are able to prevent the spread of the virus, even during these asymptomatic periods, would likely reduce the incidence of herpes. Different microbicides are being tested; some of them directly inactivate the virus, while others enhance the body’s immunity to HSV or prevent the virus from entering cells (Keller 2005). One candidate microbicide, tenofovir, was originally developed as a topical gel to prevent HIV transmission. However, it was also found in a human trial that a 1% tenofovir gel inhibited the transmission of HSV-2 by 51% (Andrei 2011; Cates 2010; Celum 2012). As a result, the use of tenofovir may become a strategy to prevent the spread of herpes, though more research is needed.
Another treatment approach for both shingles and herpes is to prevent the virus from becoming reactivated by stimulating the body’s immunity with a vaccine. A vaccine against shingles (Zostavax®) was licensed in 2006 by the US Food and Drug Administration (Tseng 2011). When administered to individuals over the age of 60 with a healthy immune system, this vaccine reduced the risk of developing shingles by 55% (Tseng 2011). Studies of this vaccine found it was safe for patients 60 years and older, with the most common side effects being swelling, redness, warmth, and pain at the vaccination site. A small percentage of participants developed a varicella-like rash, consisting of a small number of fluid-filled vesicles that occurred at the site of the injection and did not spread (Simberkoff 2010). The vaccine is widely available to the public, which means that it has the potential to greatly reduce the number of cases of shingles in the United States and in other developed countries. The biggest barrier to its widespread use is cost, as it is one of the most expensive vaccines recommended for older adults (Hurley 2010).
Researchers have also worked on a vaccine for HSV, as this is thought to be one of the most effective ways to prevent the spread of herpes (Chentoufi 2012). Many different approaches towards creating an HSV vaccine have been tried, and though some have had promising initial results, none of the vaccines tested have proven to be effective at preventing HSV-2 infection (Belshe 2012; Chentoufi 2012; Cohen 2010), but some have shown limited efficacy in preventing HSV-1 infections (Belshe 2012).
A potential explanation for this limited efficacy is that the immune cells (T cells) that facilitate vaccine-mediated immunity have a difficult time gaining access to the female genital tract in the absence of inflammation or infection, and this prevents the vaccine from successfully providing immunity against HSV-2 (Shin 2012). As a result, new approaches for vaccination are under development. One of these, the “prime and pull” approach, is a new two-step strategy, in which a conventional vaccination is performed (via the bloodstream) to generate a T-cell response (“prime”), and in the second step, a compound (called a chemokine) is applied to the genital tract to recruit the activated T cells (“pull”) (Shin 2012). More studies are needed before these vaccines become available.