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1.  Incubation periods of acute respiratory viral infections: a systematic review 
The Lancet. Infectious diseases  2009;9(5):291-300.
Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications.
PMCID: PMC4327893  PMID: 19393959
2.  Fetal and Neonatal Health Consequences of Vertically Transmitted Hepatitis E Virus Infection 
Hepatitis E virus (HEV) infections lead to tens of thousands of deaths annually, mostly in developing countries. Hepatitis E poses a significant threat to the health of expectant mothers, a well-noted epidemiologic feature of the disease, but the contribution of vertically transmitted HEV infection to fetal and neonatal morbidity and mortality has received limited attention. Evidence assembled to date suggests that mother-to-child HEV transmission may be frequent and deleterious to the fetus and newborn in pregnancies affected by hepatitis E. Additional work is required to resolve key questions. (1) What risks do subclinical maternal HEV infections and infections early in pregnancy pose to fetal health and development? (2) Does vertical transmission occur during labor and/or breastfeeding and contribute appreciably to neonatal morbidity and mortality? (3) How do treatment decisions for severely ill mothers affect fetal and neonatal outcomes? (4) Can maternal vaccination effectively prevent vertical transmission of HEV?
PMCID: PMC3919250  PMID: 24420778
3.  Host Immune Status and Response to Hepatitis E Virus Infection 
Clinical Microbiology Reviews  2014;27(1):139-165.
Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available.
PMCID: PMC3910912  PMID: 24396140
4.  A systematic review of the epidemiology of hepatitis E virus in Africa 
BMC Infectious Diseases  2014;14:308.
Hepatitis E Virus (HEV) infection is a newly recognized serious threat to global public health and Africa is suspected to be among the most severely affected regions in the world. Understanding HEV epidemiology in Africa will expedite the implementation of evidence-based control policies aimed at preventing the spread of HEV including policies for the use of available resources such as HEV vaccines.
Here we present a comprehensive review of HEV epidemiology in Africa based on published data. We searched for articles on HEV epidemiology in Africa from online databases such as PubMed, Scopus, and ISI Web of Science and critically reviewed appropriate publications to extract consistent findings, identify knowledge gaps, and suggest future studies.
Taking a particularly high toll in pregnant women and their fetuses, HEV has infected human populations in 28 of 56 African countries. Since 1979, 17 HEV outbreaks have been reported about once every other year from Africa causing a reported 35,300 cases with 650 deaths.
In Africa, HEV infection is not new, is widespread, and the number of reported outbreaks are likely a significant underestimate. The authors suggest that this is a continent-wide public health problem that deserves the attention of local, regional and international agencies to implement control policies that can save numerous lives, especially those of pregnant women and their fetuses.
PMCID: PMC4055251  PMID: 24902967
Hepatitis E; Africa; Review; Outbreak; Pregnancy
5.  Factors associated with drinking alcohol before visiting female sex workers among men in Sichuan Province, China 
AIDS and behavior  2013;17(2):568-573.
Alcohol use in commercial sex is highly prevalent globally and alcohol use in conjunction with sexual activity might increase the probability of risky behaviors, and. In the current study, we explored individual and contextual factors associated with drinking alcohol before visiting female sex workers (FSWs) among 560 male clients in Sichuan province, China. A cross-sectional survey was conducted in Sichuan province, China. Over one-fifth (21.1%) of the participants reported always using alcohol before having sex with FSWs. As compared to those who reported not always drinking alcohol before having sex with FSWs, male clients who reported always drinking alcohol before having sex with FSWs had higher income, were more likely to have main sex partners, to drink alcohol daily, to report minor depressive symptoms and were more likely to visit FSWs with friends rather than by themselves. Results from this study highlight the importance of addressing alcohol use among men who pay for sex in China. Future interventions should promote alcohol-related norms in reducing the harms associated with consuming alcohol.
PMCID: PMC4017933  PMID: 22806054
alcohol use; risky sexual behaviors; commercial sex; HIV; China
6.  Environmental Predictors and Incubation Period of AIDS-Associated Penicillium marneffei Infection in Ho Chi Minh City, Vietnam 
Humidity is a strong predictor of Penicillium marneffei hospital admissions in Ho Chi Minh City, Vietnam, suggesting that humidity may contribute to exposure of susceptible individuals. We estimate the P. marneffei incubation period to be 1 week.
Background. Penicillium marneffei is an emerging dimorphic mycosis endemic in Southeast Asia, and a leading cause of mortality among human immunodeficiency virus (HIV)–infected people in the region. Factors governing the seasonal incidence of P. marneffei infection are unknown, and may yield critical insights into possible reservoirs or modes of acquisition.
Methods. This study included HIV-infected patients presenting with P. marneffei (n = 719) and Cryptococcus neoformans (n = 1598) infection to the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from 2004 to 2010, and temperature, humidity, wind, precipitation, and HIV-related admissions data for the corresponding period. We used multivariate regression modeling to identify factors associated with P. marneffei and C. neoformans admissions. We estimated the P. marneffei incubation period by considering profile likelihoods for different exposure-to-admission delays.
Results. We found that P. marneffei admissions were strongly associated with humidity (P < .001), and that precipitation, temperature, and wind did not add explanatory power. Cryptococcus neoformans admissions were not seasonal, and P. marneffei admissions were more common relative to C. neoformans admissions during months of high (≥85%) humidity (odds ratio, 1.49; 95% confidence interval [CI], 1.10–2.01). Maximum likelihood estimation suggested a P. marneffei incubation period of 1 week (95% CI, 0–3 weeks).
Conclusions. Our findings suggest that humidity is the most important environmental predictor of P. marneffei admissions, and may drive exposure by facilitating fungal growth or spore release in the environment. In addition, it appears that a high proportion of penicilliosis patients present to the hospital with primary disseminated infection within 3 weeks of exposure.
PMCID: PMC3888300  PMID: 23386634
Penicillium marneffei; penicilliosis; seasonality; humidity; HIV/AIDS
7.  Changes in HIV Incidence among People Who Inject Drugs in Taiwan following Introduction of a Harm Reduction Program: A Study of Two Cohorts 
PLoS Medicine  2014;11(4):e1001625.
Kenrad Nelson and colleagues report on the association between HIV incidence and exposure to a national harm-reduction program among people who inject drugs in Taiwan.
Please see later in the article for the Editors' Summary
Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID.
Methods and Findings
The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6–12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06–0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates.
Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID.
Please see later in the article for the Editors' Summary
Editors' Summary
About 35 million people worldwide are currently infected with HIV, the virus that causes AIDS, and about 2.3 million people become newly infected every year. HIV is mainly transmitted through unprotected sex with an infected partner. However, people who inject drugs (PWID) have a particularly high risk of HIV infection because blood transfer through needle and syringe sharing can transmit the virus. It is estimated that 5%–10% of all people living with HIV are PWID. Indeed, in some regions of the world the primary route of HIV transmission is through shared drug injection equipment and the prevalence (the proportion of a population that has a specific disease) of HIV infection among PWID is very high. In Asia, for example, more than a quarter of PWID are HIV positive. Because the high prevalence of HIV among PWID poses a global health challenge, bodies such as the Joint United Nations Programme on HIV/AIDS endorse harm reduction strategies to prevent risky injection behaviors among PWID. These strategies include the provision of clean needles and syringes, opioid substitution therapy such as methadone maintenance treatment, and antiretroviral treatment for HIV-positive PWID.
Why Was This Study Done?
Although harm reduction strategies for combating HIV epidemics among PWID have been implemented in several countries, few large-scale studies have examined the association between HIV incidence (the proportion of new cases of HIV in a population per year) and exposure to harm reduction programs among PWID. In this cohort study (an investigation that determines the characteristics of a group of people and then follows them over time), the researchers determine the association between harm reduction programs and HIV incidence among PWID in Taiwan. HIV infections used to be rare among the 60,000 PWID living in Taiwan, but after the introduction of a new HIV strain into the country in 2003, an HIV epidemic spread rapidly. In response, the Taiwanese government introduced a pilot program of harm reduction that included the provision of clean needles and syringes and health education in July 2005. The program was expanded to include methadone maintenance treatment in early 2006 and implemented nationwide in June 2006.
What Did the Researchers Do and Find?
The researchers enrolled two study populations. The first cohort comprised 3,851 PWID who were incarcerated for illicit drug use between 2004 and 2010 and who tested positive for HIV upon admission into prison. By using the BED assay, which indicates whether an HIV infection is recent, the researchers were able to determine the HIV incidence among the prisoners. In 2004, the estimated HIV incidence among prisoners with a history of drug injection was 6.44%. The incidence peaked in 2005 at 18.2%, but fell to 0.3% in 2010.
The second study population comprised 2,473 individuals who were HIV negative on January 1, 2006, and who had been incarcerated for drug use crimes but were released on July 16, 2007, during an amnesty. The researchers regularly interviewed these participants between their release and 2010 about their use of harm reduction interventions, and obtained other data about them (for example, diagnosis of HIV infection) from official databases. Analysis of all these data indicated that, in this cohort, attendance at methadone maintenance treatment clinics and frequent use of needle and syringe services were both associated with a significantly lower HIV incidence.
What Do These Findings Mean?
These findings suggest that the introduction of a comprehensive harm reduction program in Taiwan was associated with a significant reduction in the HIV incidence rate among PWID. These findings must be interpreted with caution, however. First, because the participants in the study were selected from PWID with histories of incarceration, the findings may not be representative of all PWID in Taiwan or of PWID in other countries. Second, PWID who chose to use needle and syringe services or methadone maintenance treatment clinics might have shared other unknown characteristics that affected their risk of HIV infection. Finally, some of the reduction in HIV incidence seen during the study is likely to be associated with the availability of free treatment, which has been offered to all HIV-positive individuals in Taiwan since 1997. Despite these limitations, these findings suggest that countries with a high prevalence and incidence of HIV among PWID should provide comprehensive harm reduction services to their populations to reduce risky drug injection behaviors.
Additional Information
Please access these websites via the online version of this summary at
Information is available from the US National Institute of Allergy and Infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on injecting drug users and HIV/AIDS and on harm reduction and HIV prevention (in English and Spanish)
The US National Institute on Drug Abuse also provides information about drug abuse and HIV/AIDS (in English and Spanish)
The 2013 UNAIDS World AIDS Day report provides up-to-date information about the AIDS epidemic and efforts to halt it
Personal stories about living with HIV/AIDS are available through Avert, Nam/aidsmap, and Healthtalkonline
PMCID: PMC3979649  PMID: 24714449
8.  Screening Utility, Local Perceptions, and Care-seeking for Reported Jaundeesh among Respondents Lacking Signs of Icterus in Rural Bangladesh 
In rural Bangladesh, acute viral hepatitis presents a significant burden on the public-health system. As part of the formative work for a large epidemiologic study of hepatitis E in rural Bangladesh, we sought to identify local terms that could be used for population-based screening of acute viral hepatitis. Exploration of the local term jaundeesh for screening utility identified a high burden of reported jaundeesh among individuals without symptoms of icterus. Recognizing that local perceptions of illness may differ from biomedical definitions of disease, we also sought to characterize the perceived aetiology, care-seeking patterns, diagnostic symptoms, and treatments for reported jaundeesh in the absence of icteric symptoms to inform future population-based studies on reported morbidities. We conducted a cross-sectional survey among 1,441 randomly-selected subjects to identify the prevalence of reported jaundeesh and to test the validity of this local term to detect signs of icterus. To characterize the perceived aetiology and care-seeking patterns for jaundeesh among the majority of respondents, we conducted in-depth interviews with 100 respondents who self-reported jaundeesh but lacked clinical signs of icterus. To describe diagnostic symptoms and treatments, in-depth interviews were also performed with 25 kabirajs or traditional faith healers commonly visited for jaundeesh. Of the 1,441 randomly-selected participants, one-fourth (n=361) reported jaundeesh, with only a third (n=122) reporting yellow eyes or skin, representative of icterus; Jaundeesh had a positive predictive value of 34% for detection of yellow eyes or skin. Anicteric patients with reported jaundeesh perceived their illnesses to result from humoral imbalances, most commonly treated by amulets, ritual handwashing, and bathing with herbal medicines. Jaundeesh patients primarily sought folk and spiritual remedies from informal care providers, with only 19% visiting allopathic care providers. Although the local term jaundeesh appeared to have limited epidemiologic utility to screen for acute symptomatic viral hepatitis, this term described a syndrome perceived to occur frequently in this population. Future population-based studies conducting surveillance for acute hepatitis should use caution in the use and interpretation of self-reported jaundeesh. Further study of jaundeesh may provide insight into the appropriate public-health response to this syndrome.
PMCID: PMC3805887  PMID: 24288951
Ethnography; Hepatitis; HEV; Jaundice; Medical anthropology; Morbidity; Traditional healers; Bangladesh
9.  The seroprevalence of hepatitis C virus (HCV) among 559,890 first-time volunteer blood donors in China reflects regional heterogeneity in HCV prevalence and changes in blood donor recruitment models 
Transfusion  2010;50(7):1505-1511.
A decrease in the prevalence of hepatitis C virus antibody (anti-HCV) has been reported among voluntary blood donors in some regions of China. However, the prevalence of HCV among volunteer blood donors in other regions of China has not been reported. The aim of this study was to investigate the seroprevalence of HCV among 559,890 first-time volunteer blood donors recruited during 2004 through 2007 at the Guangzhou Blood Center, China.
Study Design and Methods
Anti-HCV was detected using two different third-generation enzyme immunoassay kits. HCV RNA was detected using reverse transcription–polymerase chain reaction (RT-PCR) targeting the 5′-untranslated region of HCV.
Among 559,890 donors, 1877 (0.335%) were positive for anti-HCV. The anti-HCV+ rate was significantly higher in males than females (0.37% vs. 0.28%; p < 0.001) and significantly lower among donors living in Guangdong Province than donors who had migrated from other locations (0.30% vs. 0.40%; p < 0.001). Among the 1877 anti-HCV+ donors, 450 were randomly selected for HCV nucleic acid amplification by RT-PCR. Of these, 270 (60%) were HCV RNA+ and 180 (40%) were HCV RNA–.
Many donors from outside Guangdong Province were migrant laborers from other areas in China, suggesting that there is regional heterogenicity in HCV prevalence within China. The overall anti-HCV+ rate reported here is among the lowest reported among blood donors in China reflecting the effect of the current recruitment of exclusively volunteer donors.
PMCID: PMC3743680  PMID: 20456675
10.  IL28B favorable genotype and ultra rapid viral response as earliest treatment predictors of sustained viral response among Georgian cohort infected with hepatitis C genotype one 
Early identification of factors contributing to successful treatment of hepatitis C infection is important for researchers and clinicians. Studies conducted on the role of ultra rapid viral response (URVR) for prediction of sustained viral response (SVR) have shown its high positive predictive value (PPV). However, data on the combined effect of URVR with IL28B genotypes for prediction of SVR are lacking. Our aim was to study the role of URVR and IL28B genotypes for prediction of SVR among patients in Georgia infected with genotype 1.
Of a total of 156 patients enrolled in the study, 143 were included in the final analyses. Viral load testing for monitoring viral response was done at 3, 24, and 48, 72 hours and at 1, 2, and 4 weeks after treatment initiation. IL28B single nucleotide polymorphisms in rs12979860 were genotyped by real time PCR methods.
Our study revealed URVR as the earliest treatment predictor among genotype 1 patients harboring IL28B C/C genotype (PPV-100%). Moreover, C/C genotype was found have a high PPV among genotype 1 patients without URVR or RVR unlike patients infected with genotype 2 or 3. URVR and IL28B C/C genotype were not as predictive of an SVR among genotype 2 and 3 patients; however RVR were highly predictive of an SVR in these patients.
Our results suggest that testing for IL28B genotypes and viral load at week one and two may improve the ability to predict an SVR among HCV genotype 1 patients; this information can be useful to encourage patients to remain on treatment.
PMCID: PMC3368996  PMID: 22569080
HCV viral load; SNPs; interferon treatment
11.  An Exploratory Case Control Study of Risk Factors for Hepatitis E in Rural Bangladesh 
PLoS ONE  2013;8(5):e61351.
Hepatitis E virus (HEV) is the major cause of epidemic and sporadic hepatitis globally. Outbreaks are associated with fecal contamination of drinking water, yet the environmental reservoir of HEV between epidemics remains unclear. In contrast to neighboring countries, where epidemics and sporadic disease co-occur, HEV-endemic communities in rural Bangladesh seldom report outbreaks; sporadic hepatitis E is reported from urban and rural areas of the country. Besides typical enteric risk factors, other routes for HEV infection and disease are unclear. We conducted monthly household surveillance of a southern Bangladeshi community of 23,500 people to find incident cases of acute hepatitis E over a 22 month period. An algorithm was used to capture 279 candidate cases, of which 46 were confirmed acute HEV infections. An exploratory case-control study was conducted to identify putative risk factors for disease. Nearly 70% of cases were over 15 years old. Female gender seemed protective (OR:0.34) against hepatitis E in this conservative setting, as was the use of sanitary latrines (OR:0.28). Socioeconomic status or animal exposures were not significant predictors of disease, although outdoor employment and recent urban travel were. Unexpectedly, recent contact with a “jaundiced” patient and a history of injection exposure in the 3 months prior to disease (OR:15.50) were significant. Susceptible individuals from “endemic” communities share similar enteric exposure risks to those commonly associated with tourists from non-endemic countries. This study also raises the novel possibility of parenteral and person-to-person transmission of HEV in non-epidemic, sporadic disease settings.
PMCID: PMC3652836  PMID: 23675410
12.  Household Risk Factors for Colonization with Multidrug-Resistant Staphylococcus aureus Isolates 
PLoS ONE  2013;8(1):e54733.
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.
PMCID: PMC3554652  PMID: 23359808
13.  Associated factors for recommending HBV vaccination to children among Georgian health care workers 
BMC Infectious Diseases  2012;12:362.
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.
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.
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.
Vaccinating health care workers against HBV may provide a dual benefit by boosting occupational safety as well as strengthening universal coverage programs for newborns.
PMCID: PMC3544730  PMID: 23256746
Hepatitis B; Vaccine; Safety; Health Care Worker; Newborns
14.  Correlation of Viral Loads with HCV Genotypes: Higher Levels of Virus Were Revealed among Blood Donors Infected with 6a Strains 
PLoS ONE  2012;7(12):e52467.
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.
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.
HCV genotype 1 and 6 had significantly higher viral loads than genotype 2 and 3.
PMCID: PMC3524124  PMID: 23285053
15.  Hepatitis E, a Vaccine-Preventable Cause of Maternal Deaths 
Emerging Infectious Diseases  2012;18(9):1401-1404.
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.
PMCID: PMC3437697  PMID: 22931753
hepatitis E; hepatitis; viruses; humans; pregnancy; pregnancy complications; maternal mortality; vaccines; hepatitis vaccines; immunization; vaccination; population surveillance; Asia; Bangladesh; Nepal; China; developing countries
16.  Molecular and Phenotypic Characteristics of Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus at a Rural Hospital 
PLoS ONE  2012;7(6):e38354.
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.
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.
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.
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.
PMCID: PMC3376098  PMID: 22719880
17.  Molecular epidemiological study of hepatitis B virus in blood donors from five Chinese blood centers 
Archives of Virology  2012;157(9):1699-1707.
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.
PMCID: PMC3431469  PMID: 22669316
18.  Analysis of Chinese Donors’ Return Behavior 
Transfusion  2010;51(3):523-530.
It is important to understand donor return behavior. Converting first time donors to become repeat donors is essential for maintaining an adequate blood supply.
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.
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.
Most of the Chinese blood supply is from first time donors. Strategies aimed at encouraging current donors to become repeat donors are needed.
PMCID: PMC3025301  PMID: 20849408
first time donor; repeat donor; donor return
19.  Changes in Blood-borne Infection Risk Among Injection Drug Users 
The Journal of Infectious Diseases  2011;203(5):587-594.
(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.
PMCID: PMC3072736  PMID: 21282191
20.  Methicillin-Resistant Staphylococcus aureus ST9 in Pigs in Thailand 
PLoS ONE  2012;7(2):e31245.
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.
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.
PMCID: PMC3281948  PMID: 22363594
21.  Neurologic Symptoms Associated With Raising Poultry and Swine Among Participants in the Agricultural Health Study 
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.
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.
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.
Occupational contact with live poultry or swine, potentially related to C. jejuni exposure, was associated with increased reporting of GBS-like symptoms.
PMCID: PMC3041019  PMID: 21270654
Guillain-Barré Syndrome; Campylobacter jejuni; peripheral neuropathy; farmer; Agricultural Health Study; swine; poultry
22.  Epidemiology and Risk Factors of Incident Hepatitis E Virus Infections in Rural Bangladesh 
American Journal of Epidemiology  2010;172(8):952-961.
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.
PMCID: PMC2984247  PMID: 20801864
Asia; Bangladesh; hepatitis E; hepatitis E virus; incidence; prevalence; seroepidemiologic studies
23.  Prevalence, Correlates, and Viral Dynamics of Hepatitis Delta Among Injection Drug Users 
The Journal of infectious diseases  2010;202(6):845-852.
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.
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.
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.
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.
PMCID: PMC2924454  PMID: 20701536
hepatitis delta virus; prevalence; hepatitis B virus; injection drug user; viral load
24.  Prevalence and Risk Factors for Hepatitis C Virus Infection among Young Thai Men 
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.
PMCID: PMC2911198  PMID: 20682895
25.  Peer norms and consistent condom use with female sex workers among male clients in Sichuan province, China 
Social science & medicine (1982)  2010;71(4):832-839.
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.
PMCID: PMC2910229  PMID: 20541859
commercial sex; peer norms; condoms; HIV; China; female sex workers; male sex clients

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