Updates by Carol A. Kemper, MD, FACP
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.
HIV Risk Triplesin Women with an STD
- Mlisana K, et al. Symptomatic vaginal discharge is a poor predictor of sexually transmitted infections and genital tract inflammation in high-risk women in South Africa. J Infect Dis 2012;206:6-14.
- Classical sexually transmitted diseases drive the spread of HIV-1: Back to the future. J Infect Dis 2012;206:1-2.
Studies of stable, heterosexually active HIV/non-HIV discordant couples demonstrate a favorably low risk of HIV transmission (estimated at 1/500 to 1/1000 episodes of coitus, depending on various factors). I find myself counseling discordant couples with the occasional condom breakage that the risk of HIV transmission is reassuringly low. Some couples have even taken advantage of this low risk, successfully risking pregnancy without transmission. So why is there an estimated 50,000 new cases of HIV occurring in the United States every year? Is there that much sex occurring out there?
Mlisana and colleagues shed light on an uncomfortable reality (see the lead article and accompanying editorial). Most cases of HIV are not occurring in otherwise healthy individuals in a stable discordant relationship. And the risk of HIV acquisition is much greater than previously recognized for a woman with an STD or cervicovaginal inflammation, even in the absence of vaginal discharge or STD symptoms.
They prospectively followed 242 South African non-HIV-infected women at high risk for HIV infection, examining them every 6 months for 2 years for the presence of vaginal discharge, STDs, cervical inflammation, and the acquisition of HIV. The women were described as having a single, stable sexual partner (33%) or multiple stable partners (57%), although additional questions revealed that at least 95% reported at least one casual sex partner in the previous 3 months, and 79% described themselves as sex workers. Regular 6-month evaluations consisted of serologies for syphilis and HIV, cervical and vaginal swabs for Bacterial vaginosis, DNA testing for gonorrhea and chlamydia trachomatis, and (in-house) PCR testing for HSV, trichomonas vaginalis, mycoplasma genitalum; as well as measurements of 42 cytokine concentrations in cervicovaginal secretions. Additional studies were performed if genital ulcers were visualized, including PCR testing for syphilis, chlamydia spp. including lymphogranuloma venereum strains, and Calymmatobacterium granulomatis.
Testing at entry to study revealed STDs in a number of the women, including trichomonas (20%), gonorrhea (5.4%), chlamydia (4.2%), and mycoplasma genitalum (1.2%). HSV-2 antibodies were present in 86%, and active HSV-2 shedding was present in 3.7%.
During the two-year follow-up, 204 were women were diagnosed with at least one STD, only 25 (12.3%) of which resulted in a symptomatic vaginal discharge. At the 6 and 12 month screening visit, respectively, 18.5% and 24% were diagnosed with one or more STDs. However, only 1.5% and 4.8% respectively, reported symptoms/vaginal discharge.
Twenty-eight women (11.6%) became HIV-infected during the 2-year study. The presence of an STD was associated with a 3-fold increased risk for HIV-infection. Among the STDs, gonorrhea, chlamydia and Mycoplasma genitalum were statistically associated with an increased risk of HIV transmission. In multivariate analysis, adjusting for various factors, gonorrhea remained significantly associated with a risk of acquiring HIV (> 7-fold unadjusted risk), presumably as the result of the significant cervical inflammation associated with this infection. HSV-2, bacterial vaginosis and vaginal discharge by itself were not statistically significant.
Sexually active sub-Saharan women are at significantly higher risk for acquiring HIV in the presence of an STD, especially gonorrhea, even if those infections are asymptomatic or do not result in clinical vaginal discharge. While aggressive screening and treatment for STDs may decrease this risk, these study authors found that even with routine 6 month screening and treatment, 11.6% of women nonetheless acquired HIV infection.
Reactivation of HBV with Chemotherapy
Lok ASF, et al. Reactivation of hepatitis B during immunosuppressive therapy: potentially fatal yet preventable. Ann Intern Med 2012;156:743-745.
Approximately 1 in 300 adults in the United States are infected with Hepatitis B virus (HBV) with a positive Hepatitis Bs Ag, and 1 in 20 may be seropositive for HBV core antibody/seronegative for HBV surface antigen. With the increasing use of anti-TNF-alpha inhibitors and more potent chemotherapeutic agents with immunosuppressive potential, reactivation of HBV infection is a real risk in the oncology and rheumatology populations. HBV reactivation is especially a problem in persons with lymphoproliferative/hematologic malignancy, but has also been reported in persons receiving chemotherapy for solid tumors, those receiving long-term corticosteroids, and those receiving anti-TNF alpha inhibitors. And yet, based on survey data, the CDC estimates that only 13% to 19% of oncologists routinely screen patients for HBV.
These authors reviewed 14 studies of HBV reactivation, including 2 randomized clinical trials, which included a total of 550 Hepatitis Bs ag-positive patients receiving chemotherapy. For those patients not receiving prophylactic antivirals, fully one-third (36.8%) had reactivation HBV infection, 13% developed liver failure and 5.5% died. Unfortunately, even if antiviral treatment is provided to these patients, the success rate is not good: severe hepatitis may still occur in 13% to 36% despite initiation of antiviral treatment. In contrast, the use of antiviral prophylaxis (e.g., lamivudine) can reduce the risk of reactivation HBV infection in patients with positive surface Ag by 79% to 100%.
While patients seropositive for HBV surface antigen are at the greatest risk for reactivation, data also suggest that Hep Bs ag-negative/Core Ab-positive persons are at risk for reactivation, especially if receiving rituximab or other anti-TNF alpha inhibitors. Rheumatologists and oncologists should screen their patients for Hepatitis Bs Ag and B core Ab (as well as a TB test and Strongyloides Ab in those at risk) and consider offering HBV antiviral prophylaxis to both groups of patients.
A Pox on You !
Viner K, et al. Transmission of varicella zoster virus from individuals with herpes zoster or varicella in school and day care settings. J Infect Dis 2012; 205: 1336-41.
Suspicions have previously been raised about the higher than expected risk of transmission of varicella zoster virus from patients with Herpes zoster (shingles) under ordinary circumstances. VZV has been detected in ventilation units used for patients hospitalized with zoster, suggesting that airborne virus is occasionally found in the rooms of patients with dermatomal zoster. Salivary samples for VZV DNA from patients with dermatomal zoster are frequently positive, and VZV DNA can be found in 18% of salivary samples at 2 weeks of antiviral therapy. Potentially infectious varicella virus was even found in the saliva of a young woman with prodromal pain who had not yet developed dermatomal lesions. Another report documented the occurrence of a small outbreak of varicella in a long-term healthcare facility, following a case of herpes zoster 15 days earlier. Laboratory investigation confirmed that 18 of 26 (69%) environmental samples taken from the bedframes, rooms, lockers, and community areas of the facility were PCR-positive for VZV identical to that isolated from 4 cases.
These reports demonstrate that patients with dermatomal zoster may be infectious in a nosocomial setting, especially to patients with a prior history of varicella with waning immunity. Virus may be shed or aerosolized from zoster lesions, and infectious virus may be present in the saliva of patients with active zoster.
Viner and colleagues examined the risk of acquisition of VZV from person with dermatomal zoster in schools and day care facilities in their community from 2003-2010.
They focused on cases of varicella occurring within 10-21 days of a reported case of dermatomal zoster or a sporadic case of varicella within the same facility. A sporadic case of varicella was defined as occurring >6 weeks after or at least 10 days before another case of varicella. The cases were stratified based on vaccine status and disease severity. Tertiary cases occurring within 10-21 days of a secondary case were also included.
During the 8-year period of observation, 2296 cases of Herpes Zoster and varicella were reported by schools or day cares. Of these, 1648 were considered primary cases, including 1358 cases of sporadic varicella. For the HZ cases, 27 (9%) were associated with the occurrence of 84 secondary cases of varicella within the same institution; 70% of these were considered mild. In contrast, 15% of the sporadic cases of varicella were associated with the occurrence of 564 cases of secondary varicella within the same institution. About 72% of these were considered mild. Most of the children (>90%) with secondary varicella had previously received at least one dose of vaccine.
Thus the risk of secondary VZV infection appeared similar, regardless of whether the index case had dermatomal zoster or varicella. In addition, transmission from either a case of zoster or varicella similarly resulted in a single case of varicella about half the time, in 2-4 secondary cases about one-third the time, and outbreaks with multiple infections 14% of the time. One case of shingles was associated with 30 secondary varicella cases over a 3-month period at one facility; and, at another facility, a single case of chickenpox resulted in 35 secondary cases over a 7-month period.
Environmental samples collected from doorknobs, computers, and desks were positive for VZV DNA from 3 of 9 elementary schools surveyed.
The authors believe the gradual reduction in naturally occurring varicella infection as the result of pre-school vaccination is leaving an environmental niche for increased transmission from persons with dermatomal zoster. It is likely that this low-grade transmission has existed forever, resulting in natural re-priming of individuals with pre-existing immunity at low risk for symptomatic re-infection — only now it is occurring in previously vaccinated children with obviously less robust immunity.
At a minimum, this represents a low cost approach to re-priming immunity at relatively low risk, in contrast to broad revaccination booster programs. All I know is that I am a whole lot more confident in my own naturally-acquired immunity.HIV Risk Triplesin Women with an STD Mlisana K, et al. Symptomatic vaginal discharge is a poor predictor of sexually transmitted infections and genital tract inflammation in high-risk women in South Africa. J Infect Dis 2012;206:6-14. Classical sexually transmitted diseases drive the spread of HIV-1: Back to the future. J Infect Dis 2012;206:1-2.
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