Antimicrobial resistance, particularly in pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), limits treatment options and increases healthcare costs. To understand patient risk factors, including household and animal contact, potentially associated with colonization with multidrug-resistant MRSA isolates, we performed a prospective study of case patients colonized with MRSA on admission to a rural tertiary care hospital. Patients were interviewed and antimicrobial resistance patterns were tested among isolates from admitted patients colonized with MRSA in 2009–10. Prevalence of resistance was compared by case-patient risk factors and length-of-stay outcome among 88 MRSA case patients. Results were compared to NHANES 2003–04. Overall prevalence of multidrug resistance (non-susceptibility to ≥four antimicrobial classes) in MRSA nasal isolates was high (73%) and was associated with a 1.5-day increase in subsequent length of stay (p = 0.008). History of hospitalization within the past six months, but not antimicrobial use in the same time period, was associated with resistance patterns. Within a subset of working-age case patients without recent history of hospitalization, animal contact was potentially associated with multidrug resistance. History of hospitalization, older age, and small household size were associated with multidrug resistance in NHANES data. In conclusion, recent hospitalization of case patients was predictive of antimicrobial resistance in MRSA isolates, but novel risk factors associated with the household may be emerging in CA-MRSA case patients. Understanding drivers of antimicrobial resistance in MRSA isolates is important to hospital infection control efforts, relevant to patient outcomes and to indicators of the economic burden of antimicrobial resistance.

Background

Most cases of hepatitis B virus (HBV) infection and subsequent liver diseases can be prevented with universal newborn HBV vaccination. The attitudes of health care workers about HBV vaccination and their willingness to recommend vaccine have been shown to impact HBV vaccination coverage and the prevention of vertical transmission of HBV. The purpose of this study was to ascertain the factors associated with health care worker recommendations regarding newborn HBV vaccination.

Methods

A cross-sectional study of prevalence and awareness of hepatitis B and hepatitis B vaccine was conducted among randomly selected physicians and nurses employed in seven hospitals in Georgia in 2006 and 2007. Self-administered questionnaires included a module on recommendations for HBV, HCV and HIV.

Results

Of the 1328 participants included in this analysis, 36% reported recommending against hepatitis B vaccination for children, including 33% of paediatricians. Among the 70.6% who provided a reason for not recommending HBV vaccine, the most common concern was an adverse vaccine event. Unvaccinated physicians and nurses were more likely to recommend against HBV vaccine (40.4% vs 11.4%, PR 3.54; 95% CI: 2.38, 5.29). Additionally, health care worker age was inversely correlated with recommendations for HBV vaccine with older workers less likely to recommend it.

Conclusion

Vaccinating health care workers against HBV may provide a dual benefit by boosting occupational safety as well as strengthening universal coverage programs for newborns.

Background

Both HCV genotypes and viral loads are predictors of therapeutic outcomes among patients treated with α-interferon plus ribavirin; however, such correlation has only been studied for genotypes 1, 2, and 3 but not for genotype 6.

Methodology/Findings

299 voluntary blood donors were recruited who were HCV viremic. Their mean age was 31.8; the male/female ratio was 3.82 (225/59). The viral loads of HCV were measured using the COBAS AmpliPrep/COBAS TaqMan test (CAP/CTM) while HCV genotypes were determined by direct sequencing the partial NS5B region. HCV genotypes 1, 2, 3, and 6 were determined in 48.9%, 8.7%, 12.3%, and 30.1% of the donors, respectively, and the levels of mean viral loads in genotype 1 and 6 significantly higher than that of 2 and 3 (P<0.001). As a whole, the viral loads in male donors were higher than in female (P = 0.006). Moreover, the donors' gender and HCV genotypes are independently correlated with the measured viral loads.

Conclusion

HCV genotype 1 and 6 had significantly higher viral loads than genotype 2 and 3.

These deaths are substantial and could be prevented by commercial vaccine.

Hepatitis E virus (HEV) is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. Although HEV vaccine trials, including trials conducted in populations in southern Asia, have shown candidate vaccines to be effective and well-tolerated, these vaccines have not yet been produced or made available to susceptible populations. Surveillance data collected during 2001–2007 from >110,000 pregnancies in a population of ≈650,000 women in rural Bangladesh suggest that acute hepatitis, most of it likely hepatitis E, is responsible for ≈9.8% of pregnancy-associated deaths. If these numbers are representative of southern Asia, as many as 10,500 maternal deaths each year in this region alone may be attributable to hepatitis E and could be prevented by using existing vaccines.

Background

While methicillin-resistant Staphylococcus aureus (MRSA) originally was associated with healthcare, distinct strains later emerged in patients with no prior hospital contact. The epidemiology of MRSA continues to evolve.

Methods

To characterize the current epidemiology of MRSA-colonized patients entering a hospital serving both rural and urban communities, we interviewed patients with MRSA-positive admission nasal swabs between August 2009 and March 2010. We applied hospitalization risk factor, antimicrobial resistance phenotype, and multi-locus sequence genotype (MLST) classification schemes to 94 case-patients.

Results

By MLST analysis, we identified 15 strains with two dominant clonal complexes (CCs)–CC5 (51 isolates), historically associated with hospitals, and CC8 (27 isolates), historically of community origin. Among patients with CC5 isolates, 43% reported no history of hospitalization within the past six months; for CC8, 67% reported the same. Classification by hospitalization risk factor did not correlate strongly with genotypic classification. Sensitivity of isolates to ciprofloxacin, clindamycin, or amikacin was associated with the CC8 genotype; however, among CC8 strains, 59% were resistant to ciprofloxacin, 15% to clindamycin, and 15% to amikacin.

Conclusions

Hospitalization history was not a strong surrogate for the CC5 genotype. Conversely, patients with a history of hospitalization were identified with the CC8 genotype. Although ciprofloxacin, clindamycin, and amikacin susceptibility distinguished CC8 strains, the high prevalence of ciprofloxacin resistance limited its predictive value. As CC8 strains become established in healthcare settings and CC5 strains disseminate into the community, community-associated MRSA definitions based on case-patient hospitalization history may prove less valuable in tracking community MRSA strains.

Although the genetic variability of hepatitis B virus (HBV) in HBV-infected patients has been extensively studied, reports on genotypes, subtypes and mutations in the S region of HBV strains from Chinese blood donors are limited. In this study, 245 blood samples from HBsAg-positive blood donors were collected from five geographically diverse blood centers in China. The S region of HBV was amplified, and the HBV genotype and subtype were determined. The amino acid sequences of the S region were aligned, and mutations related to the failure of immunization and HBsAg detection were determined. Of the 245 samples, 228 (93 %) were genotyped successfully. We found that genotypes B, C, D and A accounted for 58.8 %, 21.9 %, 6.6 % and 3.95 % of the isolates, respectively. The distribution of HBV antigen subtypes was as follows: adw (67.6 %), adr (23.3 %) and ayw (8.7 %). Mutations were present in 39 (17.1 %) of 228 samples in the major hydrophilic region (MHR) of the S region. This study demonstrated that HBV genotype/subtype B/adw was the most frequent strain circulating in HBV-infected Chinese blood donors, followed by C/adr. The occurrence of MHR mutants in HBV-infected blood donors and the potential failure to detect some of them in collected units poses a threat to transfusion safety.

Background

It is important to understand donor return behavior. Converting first time donors to become repeat donors is essential for maintaining an adequate blood supply.

Methods

Characteristics of 241,552 whole blood (WB) donations from first time (FT) and repeat (RPT) donors who donated in 2008 at the 5 blood centers in China were compared. A subset of 54,394 WB donors who donated between January 1 and March 31, 2008 were analyzed for their return behavior in 2008 following the index donation using logistic regression.

Results

Of all donations, 64% was from FT donors. Donors with self-reported previous donations tended to be male, older, married, donated larger volume (≥300mL), and were heavier in weight. Among donors who donated from January to March, 2008, 14% returned for subsequent WB donations by the end of 2008. The number of previous donations and blood collection location were the two strongest predictors for making subsequent donations. Donors with 1, 2–3 and more than 3 previous donations were 3.7, 5.7, and 11.0 times more likely to return than FT donors. Those who donated in a blood collection vehicle were 4 times more likely to return than those who donated at a blood center. Being female, younger and of a lower education level (≤ middle school) were positively associated with subsequent return blood donation during the follow-up period observed in this study.

Conclusion

Most of the Chinese blood supply is from first time donors. Strategies aimed at encouraging current donors to become repeat donors are needed.

(See the editorial commentary by Grebely and Dore, on pages 571–4.)

Background. Population-level hepatitis C virus (HCV) infection incidence is a surrogate for community drug-related risk.

Methods. We characterized trends in human immunodeficiency virus (HIV) and HCV infection incidence and HCV infection prevalence among injection drug users (IDUs) recruited over 4 periods: 1988–1989, 1994–1995, 1998, and 2005–2008. We calculated HIV and HCV infection incidence within the first year of follow-up among IDUs whose test results were negative for these viruses at baseline (n = 2061 and n = 373, respectively). We used Poisson regression to compare trends across groups.

Results. HIV infection incidence declined significantly from 5.5 cases/100 person-years (py) in the 1988–1989 group to 2.0 cases/100 py in the 1994–1995 group to 0 cases/100 py in the 1998 and 2005–2008 groups. Concurrently, HCV infection incidence declined but remained robust (22.0 cases/100 py in the 1988–1989 cohort to 17.2 cases/100 py in the 1994–1995 cohort, 17.9 cases/100 py in the 1998 cohort, and 7.8 cases/100 py in the 2005–2008 cohort; P = .07). Likewise, HCV infection prevalence declined, but chiefly in younger IDUs. For persons aged <39 years, relative to the 1988–1989 cohort, all groups exhibited significant declines (adjusted prevalence ratio [PR] for the 2005–08 cohort, .73; 95% confidence interval [CI], .65–.81). However, for persons aged ≥39 years, only the 2005–2008 cohort exhibited declining prevalence compared with the 1988–1989 cohort (adjusted PR, .87; 95% CI, .77–.99).

Conclusions. Although efforts to reduce blood-borne infection incidence have had impact, this work will need to be intensified for the most transmissible viruses, such as HCV.

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial and community-associated pathogen. Recently, livestock-associated MRSA (LA-MRSA) has emerged and disseminated in Europe and North America and now constitutes a considerable zoonotic burden in humans with risk factors of pig exposure, whereas the extent of the livestock reservoir is relatively unknown on other continents.

Methodology/Principal Findings

From March through April 2011, MRSA was identified in pigs from 3 out of 30 production holdings in Chang Mai Province, Thailand. Representative isolates were subjected to molecular characterization and antimicrobial susceptibility testing; all isolates had genotypic and phenotypic characteristics of LA-MRSA previously characterized in the region: they belonged to ST9, lacked the lukF-lukS genes encoding Panton-Valentine leukocidin, and were resistant to multiple non-β-lactam antimicrobials. However, unlike other Asian LA-MRSA-ST9 variants, they were spa type t337 and harbored a different staphylococcal cassette chromosome mec IX.

Conclusions/Significance

A novel MRSA-ST9 lineage has been established in the pig population of Thailand, which differs substantially from LA-MRSA lineages found in other areas of the continent. The emergence of novel LA-MRSA lineages in the animal agriculture setting is worrisome and poses a serious threat to global public health.

Objective

Guillain-Barré Syndrome (GBS) is the leading cause of acute peripheral neuropathy worldwide, often associated with recent foodborne infection with Campylobacter jejuni. In this cross-sectional analysis of data from the Agricultural Health Study, we tested whether swine and poultry exposure were associated with increased prevalence of GBS-like neurologic symptoms.

Methods

Using multivariate analysis, we tested the symptoms such as numbness and weakness, relevant to inflammatory peripheral neuropathies, among farmers with self-reported occupational poultry or swine exposure compared with farmers who reported no occupational animal exposure.

Results

Among swine farmers/workers, prevalence of weakness and numbness were increased (P< 0.05). Among poultry farmers/workers, prevalence of weakness and numbness were increased, but increased prevalence of weakness was not statistically significant.

Conclusions

Occupational contact with live poultry or swine, potentially related to C. jejuni exposure, was associated with increased reporting of GBS-like symptoms.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world. Most of South Asia is HEV endemic, with frequent seasonal epidemics of hepatitis E and continuous sporadic cases. This author group's epidemiologic work and clinical reports suggest that Bangladesh is HEV endemic, but there have been few population-based studies of this country's HEV burden. The authors calculated HEV infection rates, over an 18-month interval between 2003 and 2005, by following a randomly selected cohort of 1,134 subjects between the ages of 1 and 88 years, representative of rural communities in southern Bangladesh. Baseline prevalence of antibody to hepatitis E virus (anti-HEV) was 22.5%. Seroincidence was 60.3 per 1,000 person-years during the first 12 months and 72.4 per 1,000 person-years from >12 to 18 months (during the monsoon season), peaking by age 50 years and with low rates during childhood. Few of the seroconverting subjects reported hepatitis-like illness. Overall incidence was calculated to be 64 per 1,000 person-years, with 1,172 person-years followed. No significant associations were found between anti-HEV incidence and demographic or socioeconomic factors for which data were available. This is the first study to document annual HEV infection rates among “healthy” and very young to elderly subjects in a rural Bangladeshi population.

Background

Most hepatitis delta virus(HDV) prevalence estimates from the United States are over 10 years old, and HDV has shown significant temporal variation in other populations. HDV/hepatitis B(HBV) dual infection progresses rapidly, has more complications, and a different treatment regimen than HBV infection alone. Accurate estimates of prevalence and risk factors are important to help clinicians decide who to screen.

Methods

Injection drug users(IDUs) in Baltimore, MD positive for HBV serologic markers were tested for hepatitis delta antibody(HDAb) at two time periods: 1988-1989(n= 194) and 2005-2006(n=258). Those HDAb+ in 2005-2006 plus a random sample of HDAb-, HBV+ participants were tested for HDV-RNA, HBV-DNA, and HCV-RNA. Characteristics associated with HDV exposure and viremia were identified.

Results

HDV prevalence declined from 15% in 1988-1989 to 11% in 2005-2006. Among those with chronic HBV infection, prevalence increased from 29%(n=15/48) to 50%(n=19/38), p = 0.05. Visiting a shooting gallery was a strong correlate of HDAb positivity (relative risk=3.08, p=0.01). 8(32%) of those HDAb+ were HDV viremic. Viremic participants had elevated liver enzymes and more ER visits.

Conclusions

The temporal increase in HDV prevalence among those with chronic HBV infection is concerning; understanding this change should be a priority to prevent the burden from increasing.

Epidemiologic studies of hepatitis C virus (HCV) infection are unusual in developing countries, especially Thailand. We evaluated the prevalence and risk factors for HCV among military conscripts, including a sample of 5,246 men (1:30 sample), and human immunodeficiency virus (HIV)-1 positive men (N = 500) between 2005 and 2008. The HCV prevalence was 2.2% in the sampled group and 8.4% in HIV-1 sero-positives. Among the sampled group, HIV-1 infection, injection drug use (IDU) history, and unsafe injections were associated with HCV infection; adjusted prevalence rate ratios [RRs; 95% confidence intervals (CIs)] were 3.7 (1.04–12.77), 1.9 (1.04–3.54), and 1.8 (1.02–3.11), respectively. Among HIV-1 sero-positives, an IDU history and residence in southern Thailand were associated with HCV prevalence; adjusted RRs (95% CIs) were 3.5 (1.71–7.24) and 2.6 (1.18–5.61), respectively. Public health measures to prevent HCV in Thailand should focus on reducing injection drug use and other exposures to unsafe injections among young Thai men.

Despite their crucial role in HIV infection and transmission, commercial sex male clients (CSMCs) are rarely studied. The purpose of this study was to examine the relationship between peer norms and consistent condom use with female sex workers (FSWs) among CSMCs in Sichuan province, China. Male clients with peers who had paid for sex (n=562) were recruited by local health workers through snowball sampling. Measures of peer norms included 1) descriptive norms which were evaluated by perceptions of peer’s condom attitudes and behaviors with FSWs; 2) injunctive norms which were assessed by the perceived peer approval of using condoms with FSWs; and 3) communication of HIV-related topics with peers. The outcome was consistent condom use with FSWs. Results of multivariate logistic regression models revealed that consistent condom use with FSWs was significantly more likely among male clients who perceived more pro-condom descriptive and injunctive norms among their peer groups. In addition, the pattern of commercial sex visits moderated the relations between peer norms and consistent condom use with FSWs. More peer approval of condom use and more HIV-related communication were significantly associated with consistent condom use among clients who visited FSWs with friends but not among those who visited FSWs alone. The findings suggest that social activities surrounding commercial sex visits may provide an entry point for HIV prevention intervention with men who patronize FSWs and that such efforts should tap into existing dynamics of social interaction to promote pro-condom norms.

The availability of an adequate blood supply is a critical public health need. An influenza epidemic or another crisis affecting population mobility could create a critical donor shortage, which could profoundly impact blood availability. We developed a simulation model for the blood supply environment in the United States to assess the likely impact on blood availability of factors such as an epidemic. We developed a simulator of a multi-state model with transitions among states. Weekly numbers of blood units donated and needed were generated by negative binomial stochastic processes. The simulator allows exploration of the blood system under certain conditions of supply and demand rates, and can be used for planning purposes to prepare for sudden changes in the public's health. The simulator incorporates three donor groups (first-time, sporadic, and regular), immigration and emigration, deferral period, and adjustment factors for recruitment. We illustrate possible uses of the simulator by specifying input values for an -week flu epidemic, resulting in a moderate supply shock and demand spike (for example, from postponed elective surgeries), and different recruitment strategies. The input values are based in part on data from a regional blood center of the American Red Cross during –. Our results from these scenarios suggest that the key to alleviating deficit effects of a system shock may be appropriate timing and duration of recruitment efforts, in turn depending critically on anticipating shocks and rapidly implementing recruitment efforts.

Objective

To estimate the cumulative incidence of self-reported influenza vaccination (“vaccination coverage”) and investigate predictors in HIV-infected women.

Methods

In an ongoing cohort study of HIV-infected women in five US cities, data from two influenza seasons (2006-07 n=1,209 and 2007-08 n=1,161) were used to estimate crude and adjusted prevalence ratios (aPR) and 95% confidence intervals ([,]) from Poisson regression with robust variance models using generalized estimating equations (GEE).

Results

In our study, 55% and 57% of HIV-infected women reported vaccination during the 2006-07 and 2007-08 seasons, respectively. Using data from both seasons, older age, non-smoking status, CD4 T-lymphocyte (CD4) count ≥200 cells/mm3, and reporting at least one recent healthcare visit was associated with increased vaccination coverage. In the 2007-08 season, a belief in the protection of the vaccine (aPR=1.38 [1.18, 1.61]) and influenza vaccination in the previous season (aPR=1.66 [1.44, 1.91]) most strongly predicted vaccination status.

Conclusion

Interventions to reach unvaccinated HIV-infected women should focus on changing beliefs about the effectiveness of influenza vaccination and target younger women, current smokers, those without recent healthcare visits, or a CD4 count <200 cells/mm3.

Commercial sex work has re-emerged as a widespread industry since China started economic reforms in the 1980s. This study examined the role of interpersonal and venue-level factors in commercial sex male clients' (CSMCs) condom use with female sex workers (FSWs) in China. Given the heterogeneity of commercial sex industry in China, this study also aimed to explore how these factors function differently by social ranks of commercial sex work frequented by CSMCs. A cross-sectional survey was conducted with 601 CSMCs in Sichuan province, China. Human immunodeficiency virus (HIV) prevalence in this sample was 1.7%. In addition to the individual characteristics, interpersonal factor was measured by the frequency of FSWs taking the initiative in condom use and providing condoms. Venue-level factor was assessed by the frequency of the managers of commercial sex venues communicating condom use policies and the frequency of condom availability in commercial sex venues. The primary behavioral outcome was consistent condom use with FSWs. Multivariate logistic regression models revealed that consistent condom use with FSWs was significantly associated with interpersonal (adjusted odds ratio (AOR), 1.62; 95% confidence interval (CI), 1.38, 1.90) and venue-level factors (AOR, 1.98; 95% CI, 1.40, 2.80). Moreover, the associations between interpersonal and venue-level factors and consistent condom use were moderated by social ranks of commercial sex work frequented by the male clients. The present study findings underscore the need for comprehensive HIV prevention approaches that integrate individual, interpersonal, and venue-level factors to reduce HIV risk behaviors among CSMCs in China.

Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm3. During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216 cell/mm3 and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV.

Injection drug users (IDU) are widely believed to have accelerated the looming HIV/AIDS epidemic now faced by the Russian Federation and countries of the former Soviet Union. However, IDUs may be heterogeneous with regard to risk behaviors and a sub-population may be responsible for the majority of blood-borne pathogen transmission. We studied 926 adult injection drug users (IDU) from the cities of Tbilisi, Batumi, and Poti in Georgia, a small country in the Caucuses region between the Black and Caspian Seas, between 1997 and 1998. Study participants were administered a confidential questionnaire and were tested for antibody to HIV, hepatitis C virus (HCV), hepatitis B virus surface antigen (HBsAg), and hepatitis B core antibody (anti-HBc). Five (0.5%) individuals were positive for HIV, 539 (58.2%) for HCV, 67 (7.2%) for HBsAg, and 475 for (51.3%) for anti-HBc. 88.7% of the surveyed individuals reported sharing needles with others, and needle sharing with more than ten other individuals versus no sharing was a highly significant predictor (OR: 278.12, 95% CI: 77.57, 997.20) of HCV seropositivity. In adjusted analysis, individuals who usually injected stolen medical/synthetic drugs had significantly lower odds of HCV (OR: 0.38, 95% CI: 0.22, 0.68) and HBV (OR: 0.58, 95% CI: 0.37, 0.90) than individuals most commonly injecting opium. Despite some limitations, these results suggest the presence of substantial heterogeneity between different injection drug-using groups in Georgia. Identification of high risk IDU sub-populations is vital to efficiently target risk reduction programs, and to prevent confounding by risk status in large HIV/AIDS behavioral intervention and vaccine trials.

Background

Hepatitis E virus (HEV) is prevalent and causes disease worldwide, but its epidemiological profile is only partially understood.

Methods

We used an enzyme immunoassay to measure anti-HEV immunoglobulin G antibodies in 18,695 serum samples collected in the Third National Health and Nutrition Examination Survey. We calculated estimates of HEV seroprevalence and examined associations with putative risk factors.

Results

The seroprevalence of HEV in the civilian noninstitutionalized United States (US) population during the period from 1988 through 1994 was 21.0% (95% confidence interval [CI], 19.0%–22.9%). Among US-born individuals, males, non-Hispanic whites, and individuals residing in the Midwest and/or in metropolitan areas had the highest seroprevalence estimates. Having a pet in the home (odds ratio [OR], 1.19 [95% CI, 1.01–1.40]) and consuming liver or other organ meats more than once per month (OR, 1.38 [95% CI, 1.01–1.88]) were significantly associated with increased odds of HEV seropositivity.

Conclusions

Exposure to HEV is common in the US population, although hepatitis E is rarely reported. Having pets and consuming organ meats may play a role in HEV transmission in the United States, but other mechanisms of transmission may also exist. HEV may be considered a possible etiologic agent of acute and chronic hepatitis in US patients reporting no travel history.

Summary

Objectives

To determine prevalence, risk factors, and simple identification algorithms for HIV, hepatitis B, and hepatitis C co-infection; factors that may predispose for anti-tuberculosis therapy-induced hepatoxicity.

Methods

We recruited 300 individuals at in-patient tuberculosis hospitals in three cities in Georgia, administered a behavioral questionnaire, and tested for antibody to HIV, hepatitis C (HCV), hepatitis B core antigen (anti-HBc), and the hepatitis B surface antigen (HBsAg).

Results

0.7% of the individuals were HIV positive, 4.3% were HBsAg positive, 8.7% were anti-HBc positive, and 12.0% were HCV positive. In multivariable analysis, a history of blood transfusion, injection drug use, and prison were significant independent risk factors for HCV, while a history of blood transfusion, injection drug use, younger age at sexual debut, and a high number of sex partners were significant risk factors for HBV. Three-questionnaire item algorithms predicted HCV serostatus 74.1% of the time and HBV serostatus 85.2% of the time.

Conclusions

Treatment of tuberculosis patients in resource-limited countries with concurrent epidemics of HCV, HBV, and HIV may be associated with significant hepatoxicity. Serologic screening of tuberculosis patients for HBV, HCV and HIV or using behavioral algorithms to identify patients in need of intensive monitoring during anti-tuberculosis therapy may reduce this risk.

Injection drug use and associated hepatitis C virus (HCV) and HIV infections are on the rise in Russia and the republics of the former Soviet Union. While small targeted studies have found widespread drug use and disease among at-risk populations, there have been few attempts to comprehensively evaluate the extent of these epidemics in general post-Soviet societies. We conducted a two-stage cluster randomized survey of the entire adult population of T'bilisi, Republic of Georgia and assessed the burden of HCV, HIV, and risk behaviors for blood-borne infections in 2,000 study participants. Of the 2,000 surveyed individuals, 162 (8.1%) had injected illicit drugs during their lifetimes. Of the individuals who had injected illicit drugs, 138 (85.2%) reported sharing needles with injection partners. HCV was found in 134 (6.7%) of the total surveyed population, but in 114 (70.4%) of those who had injected illicit drugs. We found HIV in only three (0.2%) individuals, all of whom had injected illicit drugs. Injection drug use and high-risk injection practices are very common in Georgia and may be harbingers of a large burden of HCV-associated liver diseases and a potentially serious HIV epidemic in the years to come.

We evaluated a quantitative enzyme immunoassay (trak-C) for hepatitis C virus core antigen (HCV core Ag) by testing serum specimens from 820 injection drug users in Thailand with anti-HCV antibodies. The HCV genotypes in this population include genotypes 3 and 6, which have not been extensively tested with this assay. Among these specimens, 629 (76.7%) yielded positive results, with HCV core Ag concentrations predominantly spanning (35.7%) or above (58.2%) the measurable range of 1.5 to 100 pg/ml. To assess reproducibility, we retested 30 specimens representing six core Ag ranges; the mean coefficient of variation for each range was ≤9.7% (highest for 1.5 to 25 pg/ml). We also tested 204 specimens of the 820-specimen set for HCV RNA: while 146 (71.6%) were core Ag positive, 168 (82.4%) had detectable HCV RNA, of which 96% were typeable as genotype 3 (39%), 1 (31%), or 6 (26%) by nested reverse transcription-PCR. Among RNA-positive specimens, 86.9% had core Ag; 94% of the RNA negatives were core Ag negative. While there was no apparent bias for detecting core Ag representing the tested genotypes, median quantified results were higher for types 1a and 6 than for genotype 3 (P = 0.01); similarly, the median core Ag concentration was higher in HCV-human immunodeficiency virus-coinfected subjects than in HCV-monoinfected subjects. Our results demonstrated a good correlation between core Ag and HCV RNA in this population with high frequencies of genotypes 3 and 6. Because most core Ag concentrations were greater than those in the measurable range, we recommend a 10-fold dilution of the specimen before quantification. Reproducibility, low technical requirements, and high throughput should make this assay useful for clinical or research monitoring of HCV levels during active infection.

In studies of acute hepatitis C virus (HCV) infection, the early host immune response is one of the determinants of viral persistence. The class I human leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are integral components of this response. We hypothesized that the highly polymorphic HLA genes affect the outcome of an HCV infection. To test this hypothesis, we molecularly typed 231 persons with well-documented clearance of an HCV infection and 444 matched persistently infected persons. HLA-A*1101 (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.27 to 0.89), HLA-B*57 (OR, 0.62; 95% CI, 0.39 to 1.00), and HLA-Cw*0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with viral clearance, whereas HLA-A*2301 (OR, 1.78; 95% CI, 1.01 to 3.11) and HLA-Cw*04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence. HLA-Cw*04 is in strong linkage disequilibrium with HLA-B*53 and HLA-B*35, but only HLA-B*53 (OR, 1.70; 95% CI, 0.95 to 3.06) and the Cw*04-B*53 haplotype (OR, 1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA-B*53 has similar, but not necessarily identical, binding specificity to some HLA-B*35 subtypes (B*35-Px group). The association with the B*35-Px group was less strong than with HLA-B*53 alone. The association of HLA-Cw*04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy). However, HLA-Cw*04 was not associated with HCV RNA levels among the persistently infected individuals. Since Cw*04 is a ligand for the killer immunoglobulin-like receptors on natural killer cells, these cells may be involved in recovery from HCV infection. Further investigation is needed to understand the relationship between class I alleles and HCV clearance.