Updates

By Carol A. Kemper, MD, FACP, Section Editor: Updates, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor for Infectious Disease Alert.

The inheritance of HSV outbreaks

Kriesel JD, et al. C21org91 genotypes correlate with herpes simplex labialis (cold sore) frequency: Description of a cold sore susceptibility gene. Rev Infect Dis 2011; 204: 1654- 62.

Labial HSV is a remarkably common infection, and is now believed to infect ~70% of the population in the U.S.. Many of these people have only an infrequent outbreak or are unaware of their latent infection. But there are also those unfortunate individuals who develop outbreaks every 1-2 months. A good way of explaining this to patients infected with HSV is that approximately half of the people infected with HSV have had a recognizable outbreak; the rest are probably unaware of their latent infection. Of the half who have identifiable outbreaks, half of those experience more frequent outbreaks (> 2-4 per year), and the other half few to none. Why the difference? Why does my mother get a horrible outbreak with every cold or flu? And my father and I get one small lesion perhaps every 2-3 years ? Why is my latent infection more like my father's ?

Of course, the frequency of recurrent HSV outbreaks has a lot to do with the infecting strain, the infecting inoculum, and the amount of latent virus. Host and environmental factors also play a huge role (sun, wind, stress and immunosuppression). But a third and lesser understood factor is genetics. It has been recognized that certain alleles protect against HSV outbreaks. Since haplotypes are inherited in blocks, certain clusters of genes, or single nucleotide polymorphisms (SNPs), are generally inherited from one parent en bloc.

The investigators therefore examined specific gene sequences in a 3-megabase region of chromosome 21, containing 6 candidate genes possibly associated with the more frequent development of cold sores. DNA samples from a total of 618 people were collected, including 43 three- generation families. Of these, 97 individuals were frequently affected (>2 outbreaks per year), 96 were unaffected, and 162 were seropositive but with an unknown frequency of outbreaks.

Single nucleotide polymorphisms (SNPs) scans of the candidate gene sequences were examined. Following initial attempts to identify candidate genes, 45 SNP fragments within the area of interest remained. Two genes emerged as potentially linked with cold sore frequency – one within the C21orf91 gene and the other within the "chondrolectin gene". Further dominant and recessive analysis did not provide confirmatory support for the latter, but did suggest the C21orf91 gene as the likely culprit. Subsequent parenTDT trio analysis confirmed an association with HSC frequency within families (which examined whether SNP sequences are transferred from parent to child more frequently than expected by chance). Among the participants, 5 common haplotypes were identified; those with haplotype 4 and 5 had a mean number of 1.8-2.03 outbreaks per year; whereas individuals with haplotype 3 had the lowest mean of 1. 16 outbreaks per year.

The authors themselves describe this as an obscure gene – which has an open reading frame of 239 amino acids and encodes for an unknown protein. It is not yet known whether this gene is controlling the frequency of HSV infection; or is in turn controlled by regulatory genes outside of this region. Of interest, the coxsackie and adenovirus receptor genes have been identified in this same region of chromosome 21.

Are Bleach Baths a Good Solution For Staph Colonization ?

Fritz SA, et al. Effectiveness of Measures to eradicate Staphylococcus aureus carriage in patients with community-associated skin and soft-tissue infections: A randomized trial. Infect Control Hosp Epidemiol 2011; 32 (9): 872-880.

Staphylococcus infections are a hot topic in our community, and I am frequently asked to consult on patients with recurrent skin and soft tissue infections (SSTI) for "decolonization", although it is not clear what to do with most of these patients. There are no currently available protocols or public health policies advocating routine decolonization measures. I do find that while some patients scrub their hands, sinks and toilets 50 times a day till their hands are chapped and cracked, other patient's personal hygiene habits are poor. Some patients don't bathe daily — or they will quickly jump in the shower and throw a little soap on their bodies with their hands.

Over the years, I've learned to spend more time counseling people about basic hygiene: I recommend a good daily shower with an antibacterial bar of soap (not a pump or gel), that is left to dry between uses; they should use warm but not hot water, so the skin does not become overly dry; I recommend using a good soapy cotton washcloth, firmly applied to the skin in a circular motion, with special attention to the axillary areas, groin and buttocks; they should toss out their loofahs and plastic sponges; and I recommend good skin care, especially for people with dry skin, using a good moisturizer. I also recommend washing towels and washcloths in hot water and a dryer after every few days, and bedsheets at least weekly. I am impressed at how many patients (with recurrent skin infections) do not do these things as a matter of routine. I was therefore pleased to see the following report with included similar instructions in a decolonization protocol.

These authors performed an open-label randomized clinical trial examining various topical measures plus educational intervention in the reduction of Staphylococcus aureus colonization in patients with SSTI. After screening for devices, dialysis, residence in a long-term care facility, or post-operative wound infection, a total of 300 people (193 children and 107 adults) were enrolled. One-third had pets in the household, 90% had a permanent living situation, and 9-17% had more than 2 people in a bedroom. They were randomized to one of four groups: education alone (which formed the control group), or education plus one of three different topical regimens for a total of 5 days: 2% mupirocin to the anterior nares BID; mupirocin to the nares plus daily 4% chlorhexidine body washes; and mupirocin plus daily dilute bleach baths. Bleach bath instructions were to sit in a tub of warm water and ¼ cup of bleach (6% sodium hypochlorite, Chlorox®) for 15 minutes. Education consisted of instructions regarding personal and household hygiene, including washing sheets weekly, washing towels and washcloths after every use, replacing all lotions and make-ups in jars with pumps or pour bottles, and not sharing personal items with other household members. Repeat swab cultures of nares, axilla, and groin were performed at baseline, 1, 4 and 6 months. The primary outcome of the study was the eradication of Staphylococcus carriage at one month.

Of those 244 participants with available 1–month colonization data, 38% in the control (education alone) group were Staph-free compared with 56%, 55% and 63% in mupirocin, mupirocin + chlorhexidine body washes, or mupirocin + bleach baths, respectively (P = .03, .05, and .006, respectively). Of those 229 individuals with 4-month colonization data, 48% in the control group were Staph-free compared with 56%, 54% and 71% in the other 3 groups, respectively. Despite these various measures, 20% of participants developed recurrent SSTI within one month, 36% within 4 months, and 49% within 6 months of the intervention. A statistically significant reduction in SSTI was observed only in those patients receiving educational intervention + mupirocin + chlorhexidine body washes. None of the other interventions were observed to result in a statistically significant reduction in SSTI.

Follow-up phone calls to assess adherence to the recommended regimen indicated that about 80% of participants thought the instructions were easy to follow. Participants reported they followed the instructions 72% of the time for the educational group; 64% in the educational group + mupirocin; 70% in the mupirocin + chlorhexidine body baths group; and 62% in the mupirocin + bleach bath group. Therefore, only about two-thirds of participants followed the recommendations.

All of these measures are relatively easy to follow and low cost, although the bleach bathes are the most affordable intervention. A limitation may be whether patients have access to a bathtub. It is notable that nearly half (48%) of those with personal hygiene education alone were culture-negative at 4 months.