Seroprevalence of antibodies to hepatitis A and E viruses in pediatric age groups in Turkey

Hepatitis A and hepatitis E are enteric transmitted viral diseases occurring in epidemic and sporadic forms especially in developing countries. Previous studies in Turkey showed that most residents are infected with HAV by the second decade of life. Since HEV is generally transmitted by the same route as HAV we conducted a community-based seroprevalence study for HAV and HEV infection in Ahatli area in Antalya, Turkey where socioeconomic conditions are low. Anti-HAV total immunoglobulin was tested by using a microparticle EIA (Axsym-Abbott Lab). Anti-HEV IgG was assayed by a micro ELISA method (Genelabs-Singapore). Of the 338 sera tested, 112 (33.1%) were positive for anti-HAV total antibody. Anti-HEV IgG was detected in three (0.89%) of the serum samples. Seropositivity rates of HAV in preschool and school children were 19.9% and 43.9% respectively (p < 0.001). No antibody to HEV was detected in preschool children, while the prevalence of anti-HEV IgG was 1.6% in children attending school. Our data showed that seroprevalence of anti-HAV is high among children samples but HEV infection appears to be relatively rare in pediatric age groups.     

Hepatitis E virus infection in selected Brazilian populations

A retrospective study on the prevalence of hepatitis E virus (HEV) infection was conducted in selected populations in Rio de Janeiro, Brazil. A total of 1,115 subjects were tested including 146 patients with acute Non-A Non-B Non-C (NANBNC) viral hepatitis, 65 hemodialysis patients, 93 blood donors, 102 intravenous drug users (IVDUs), 304 pregnant women, 145 individuals living in the rural area and 260 individuals living in the urban area. In order to characterize a favorable epidemiological set for enterically transmitted infection in the studied populations we also evaluated the prevalence of anti-HAV IgG (hepatitis A virus) antibodies. Specific antibodies to HEV (anti-HEV IgG) were detected by a commercial EIA and specific antibodies to HAV (anti-HAV IgG) were detected using a competitive "in house" EIA. We found a high prevalence of anti-HAV IgG in these populations, that could indicate some risk for infections transmitted via the fecal-oral route. The anti-HEV IgG prevalence among the different groups were: 2.1% in patients with acute NANBNC viral hepatitis, 6.2% in hemodialysis patients, 4.3% in blood donors, 11.8% in IVDUs, 1% in pregnant women, and 2.1% in individuals form the rural area. Among individuals living in the urban area we did not find a single positive serum sample. Our results demonstrated the presence of anti-HEV IgG in almost all studied populations; however, further studies are necessary to establish the real situation of HEV epidemiology in Rio de Janeiro, Brazil.     

Seroprevalence of Hepatitis E Virus Infection among Swine Farmers and the General Population in Rural Taiwan

Objectives

Hepatitis E virus (HEV) is an emerging pathogen. We evaluated the seroprevalence of HEV infection among swine farmers and the general population in Taiwan, a nonendemic country.

Methods

We conducted a cross-sectional seroepidemiologic study in rural Taiwan in 2012 and 2013. The study included swine farmers, health examination attendees, pregnant women, and students. A commercial enzyme-linked immunosorbent assay was used to detect immunoglobulin G (IgG) and IgM against HEV. Pertinent information was collected using a questionnaire.

Results

In total, 660 participants were enrolled in the study, including 156 swine farmers, 314 health examination attendees, 100 pregnant women, and 90 students. IgG anti-HEV was detected in 29.5% of swine farmers, 11.5% of health examination attendees, 2% of pregnant women, and 1.1% of students. Two subjects were positive for IgM anti-HEV. Logistic regression analysis revealed that swine farmers had an approximately 3.5-fold increased risk (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.91–6.27; p<0.0001) for being seropositive for IgG anti-HEV as compared to the general population. Age was positively associated with seropositive rate (OR, 1.07 per year; 95% CI, 1.05–1.09; p<0.0001).

Conclusion

HEV infection is prevalent in Taiwan. The seroprevalence of HEV infection is high in swine farmers and in the elderly population.     

Swine Is a Possible Source of Hepatitis E Virus Infection by Comparative Study of Hepatitis A and E Seroprevalence in Thailand

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in developing countries are associated with contaminated food or water. Although Thailand is non-endemic for HEV, sporadic infections may occur from zoonotic transmission. Individuals between 7 months to 69 years (mean age = 32.8) from predominantly Islamic Narathiwat (n = 305) and swine farm-dense Lop Buri (n = 416) provinces were screened for anti-HEV and anti-HAV antibodies by commercial enzyme-linked immunosorbent assay and automated chemiluminescent microparticle immunoassay, respectively. Seroprevalence and relative antibody titers were analyzed according to age groups. HAV IgG antibody positive rates in Lop Buri and Narathiwat residents were 39.9% and 58%, respectively (p < 0.001). Greater than 90% of individuals >50 years old in both provinces possessed anti-HAV IgG. In contrast, seroprevalence for anti-HEV IgG was much higher in Lop Buri (37.3%) than in Narathiwat (8.9%) (p < 0.001). Highest anti-HEV IgG prevalence was found among 21-30 year-olds (50%) in Lop Buri and 41-50 year-olds (14.1%) in Narathiwat. In summary, fewer individuals possessed anti-HEV IgG in Narathiwat where most residents abstained from pork and fewer swine farms are present. Therefore, an increased anti-HEV IgG seroprevalence was associated with the density of swine farm and possibly pork consumption. Adults were more likely than children to have antibodies to both HEV and HAV.     

Seroepidemiological markers of enterically transmitted viral hepatitis A and E in individuals living in a community located in the North Area of Rio de Janeiro,RJ, Brazil

We investigated the seroprevalence of hepatitis A virus (HAV) and hepatitis E virus (HEV) infection in subjects living in the community of Manguinhos, Rio de Janeiro, Brazil, and assisted at the Health Unit of Escola Nacional de Saúde Pública, Funda??o Oswaldo Cruz. After formal consent, individuals were submitted to an interview using a standardized questionnaire. Anti-HAV and anti-HEV antibodies were detected by ELISA. Statistical analysis was carried out using the Epi-Info 6.04b software, to investigate possible associations between serological markers and risk factors. Results were regarded as significant when p value < 0.05. Although a high prevalence of anti-HAV was observed (87%), almost 50% of subjects under the age of 10 were susceptible to HAV infection, an unexpected rate in endemic areas. This fact could be attributed to improvements in environmental sanitation, occurring in this area in the last years. The increasing proportion of susceptible people may result in outbreaks of HAV infection, since the virus still circulates in this area, as verified by the detection of anti-HAV IgM in some individuals. No statistical association was met between HAV infection and the risk factors here assessed. The anti-HEV IgG prevalence found in this population was 2.4%, consistent with the one found in non-endemic areas.     

Declining Trend of Hepatitis A Seroepidemiology in Association with Improved Public Health and Economic Status of Thailand

Hepatitis A virus (HAV) is transmitted via the fecal-oral route from contaminated food or water. As part of the most recent survey of viral hepatitis burden in Thailand, we analyzed the current seroprevalence of HAV in the country and compared with data dating back to 1971. From March to October, 2014, a total of 4,260 individuals between one month and 71 years of age from different geographical regions (North = 961; Central = 1,125; Northeast = 1,109; South = 1,065) were screened for anti-HAV IgG antibody using an automated chemiluminescent microparticle immunoassay. Overall, 34.53% (1,471/4,260) possessed anti-HAV IgG antibody, and the age-standardized seroprevalence was 48.6%. Seroprevalence rates were 27.3% (North), 30.8% (Central), 33.8% (Northeast) and 45.8% (South) and were markedly lower than in the past studies especially among younger age groups. The overall trend showed an increase in the age by which 50% of the population were anti-HAV IgG antibody: 4.48 years (1971–1972), 6 (1976), 12.49 (1990), 36.02 (2004) and 42.03 (2014).This suggests that Thailand is transitioning from low to very low HAV endemicity. Lower prevalence of HAV correlated with improved healthcare system as measured by decreased infant mortality rate and improved national economy based on increased GDP per capita. The aging HAV immuno-naïve population may be rendered susceptible to potential HAV outbreaks similar to those in industrialized countries and may benefit from targeted vaccination of high-risk groups.     

Seroepidemiology of Toxoplasma gondii Infection among Healthy Blood Donors in Taiwan

Toxoplasma gondii is an opportunistic, zoonotic pathogen with a worldwide distribution. There are large variations in the seroprevalence of T. gondii infection in different regions of the world. Although toxoplasmosis became a notifiable communicable disease in Taiwan in 2007, little is known about its epidemiology among the general population. This cross-sectional study aimed to survey the seroprevalence of T. gondii infection and its risk factors among healthy blood donors in Taiwan. Through collaborating with the Taiwan Blood Services Foundation, a total of 1,783 healthy blood donors from all six-branch blood service centers participated in this study. The blood samples were tested for the presence of T. gondii antibodies and DNA using enzyme immunoassays and real-time PCR, respectively. Structured questionnaires were used to gather information on risk factors for T. gondii infection. Of the 1,783 participants, 166 (9.3%) tested positive for anti-Toxoplasma IgG, while 5 (0.28%) tested positive for anti-Toxoplasma IgM. The five IgM positive donors had high avidity antibodies suggestive of past infection. No active parasitemia was detected by real-time PCR assays. Multivariate logistic regression showed that undercooked pork meat consumption (adjusted odds ratio [OR] = 2.9; 95% confidence interval [CI]: 1.3–6.5), raw mussels consumption (adjusted OR = 5.3; 95% CI: 1.5–19.1), having a cat in the household (adjusted OR = 2.0; 95% CI: 1.2–3.2), a lower education level (adjusted OR = 1.6; 95% CI: 1.1–2.3), and donation place in eastern Taiwan (adjusted OR = 2.5; 95% CI: 1.6–3.9) were independent risk factors for Toxoplasma seropositivity. These findings provide information on the seroprevalence and epidemiology of T. gondii infection among healthy blood donors in Taiwan.     

Epidemiology of Hepatitis E Virus in China: Results from the Third National Viral Hepatitis Prevalence Survey, 2005–2006

In China, hepatitis E virus (HEV) is prevalent and causes disease, but its epidemiological profile is not well understood. We used a commercial enzyme-linked immunosorbent assay to detect total antibodies to hepatitis E virus in 15,862 serum samples collected during the Third National Viral Hepatitis Prevalence Survey. The results were analyzed to calculate estimates of HEV seroprevalence and to examine the effects of some putative risk factors. The seroprevalence of HEV in the general Chinese population during the period from 2005 through 2006 was 23.46% (95% confidence interval [CI], 18.41%–28.50%). The farming population, the age group of 15–60 year olds, and those living in the Midwest or Mideast region and in Xinjiang province had the highest seroprevalence estimates. The prevalence of HEV is high in China. The seroprevalence rate of HEV shows an unbalanced distribution among areas with different geographic location and economic development levels. The characteristics of the distribution associated may be due to the route of HEV transmission (via contaminated water or animal reservoirs). Within the same region, the seroprevalence of HEV is generally increased with age.     

Shifting seroepidemiology of hepatitis A in Japan, 1973-2003

BACKGROUND: Hepatitis A infection is caused by hepatitis A virus (HAV) contracted through fecal-oral transmission. Life-long immunity is conferred after infection. Improved sanitary conditions have generally resulted in a significant decline in the incidence of hepatitis A. However, a low incidence of infection results in increased HAV susceptibility. The present study investigates the prevalence of anti-HAV antibody and clarifies the current HAV status and HAV susceptibility in Japan at 2003. METHODS: A total of 2,430 serum specimens collected during 2003 from Japanese individuals ranging in age from 0-92 years, were tested for anti-HAV antibody using an inhibition enzyme linked immunosorbent assay. All specimens were obtained from the WHO and the National Serum Reference Bank/National Institute of Infectious Diseases, Tokyo, Japan. RESULTS: The overall seroprevalence was 12.2%. Anti-HAV antibodies were rarely detected in individuals between 0-44 years of age. Starting from the age of 45-49 years, seropositivity gradually increased through age 65 years and above. Seroprevalence was not affected by gender, and geographic distribution did not affect age-specific seroprevalence until the age of 60 years. CONCLUSIONS: HAV susceptibility in Japan is increasing annually. Particularly, the prevalence of anti-HAV antibody in individuals older than 50 years in 2003 was 50.3%, which is significantly lower than that of corresponding studies in 1994 (74.3%), 1984 (96.9%) and 1973 (96.9%). The growing susceptible population of advanced age results in more frequent HAV infection among them. The surveillance of anti-HAV antibody prevalence is useful for implementing preventive measures and for controlling the spread of HAV.     

Hepatitis E Virus in Cambodia: Prevalence among the General Population and Complete Genome Sequence of Genotype 4

Hepatitis E virus (HEV) is a growing public health problem in many countries. In this study, we investigated HEV seroprevalence among the general population in the Siem Reap province, Cambodia, and performed HEV genetic analysis with the aim to develop an HEV prevention strategy. This seroepidemiological cross-sectional study conducted from 2010 to 2014 included 868 participants from four different locations in Siem Reap province, Cambodia. They answered questionnaires and provided blood samples for the analysis of hepatitis virus infections. Among the participants (360 men and 508 women; age range, 7–90 years), the prevalence of anti-HEV IgG was 18.4% (95% confidence interval: 15.9–21.0); HEV RNA was detected in two participants (0.23%) and was classified as genotype 3 and 4. Full-length genome of the genotype 4 isolate, CVS-Sie10, was sequenced; it contained 7,222 nucleotides and three ORFs and demonstrated high sequence identity with the swine China isolates swGX40 (95.57%), SS19 (94.37%), and swDQ (91.94%). Multivariate logistic regression analysis revealed that men, elderly people, and house workers were risk groups significantly associated with the positivity for anti-HEV IgG. This is the first report on the detection of HEV genotype 4 in humans in Cambodia and on the complete genome sequence of HEV genotype 4 from this country. Our study demonstrates that new HEV infection cases occur frequently among the general population in Cambodia, and effective preventive measures are required.     

Burden of congenital rubella syndrome (CRS) in India based on data from cross-sectional serosurveys, 2017 and 2019–20

BackgroundIndia has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal.MethodsWe conducted serosurveys in 2019–20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS.ResultThe seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4–84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49–232.41) and 65.47 per 100,000 live births (95% CI: 41.60–104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225–23,100) and 50,028 (95% CI: 48,234–51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively.ConclusionsOur findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.     

Seroprevalence and Incidence of hepatitis E in Blood Donors in Upper Austria

Background

In recent years various studies showed, that hepatitis E virus (HEV) is a growing public health problem in many developed countries. Therefore, HEV infections might bear a transmission risk by blood transfusions. The clinical relevance still requires further investigations. The aim of this study was to provide an overview of acute HEV infections in Upper Austrian blood donors as well as a risk estimation of this transfusion-related infection.

Methods and Findings

A total of 58,915 blood donors were tested for HEV RNA using a commercial HEV RT-PCR Kit. 7 of these donors (0.01%) were PCR-positive with normal laboratory parameters in absence of clinical signs of hepatitis. Viral load determined by quantitative real-time PCR showed a HEV nucleic acid concentration of 2,217 293,635 IU/ml. At follow-up testing (2–11 weeks after donation) all blood donors had negative HEV RNA results. Additionally, genotyping was performed by amplification and sequencing of the ORF1 or ORF2 region of the HEV genome. All HEV RNA positive donor samples revealed a genotype 3 isolate. For the antibody screening, anti-HEV IgM and IgG were detected by ELISA. Follow up serological testing revealed that no donor was seropositive for HEV IgM or IgG antibodies at time of donation. Moreover, we verified the prevalence of anti-HEV IgG in 1,203 of the HEV RNA negative tested blood donors. Overall 13.55% showed positive results for anti-HEV IgG.

Conclusions

In the presented study, we investigated HEV infections in blood donations of Upper Austria over 1 year. We concluded that 1 out of 8,416 blood donations is HEV RNA positive. Seroprevalence of anti HEV IgG results in an age-related increase of 13.55%. Therefore, based on this data, we recommend HEV-PCR screening to prevent transmission of hepatitis E virus by transfusion.     

Hepatitis E virus as a Cause of Acute Hepatitis in The Netherlands

Background

Recent studies indicate that 27% of Dutch blood donors have evidence of past infection with HEV. However, the low number of diagnosed HEV infections indicates either an asymptomatic course or under diagnosis.

Objectives

We investigated whether HEV is a cause of acute hepatitis in Dutch patients and which diagnostic modality (serology or PCR) should be used for optimal detection.

Study design

Serum samples were retrospectively selected from non-severely immuno-compromised patients from a university hospital population, suspected of having an infectious hepatitis. Criteria were: elevated alanine aminotransferase (ALT> 34 U/l) and request for antibody testing for CMV, EBV or Hepatitis A (HAV).

Results

All samples were tested for HEV using ELISA and PCR. Ninety patients/sera were tested, of which 22% were HEV IgG positive. Only one serum was IgM positive. HEV PCR was positive in two patients: one patient was both HEV IgM and IgG positive, the other patient was only IgG positive. Both HEV RNA positive samples belonged to genotype 3. Evidence of recent infection with CMV, EBV and HAV was found in 13%, 10% and 3% respectively.

Conclusions

Although our study is limited by small numbers, we conclude that HEV is a cause of acute hepatitis in hospital associated patients in The Netherlands. Moreover, in our study population the prevalence of acute HAV (3%) was almost similar to acute HEV (2%). We propose to incorporate HEV testing in panels for acute infectious hepatitis. Negative results obtained for HEV IgM in a HEV PCR positive patient, indicates that antibody testing alone may not be sufficient and argues for PCR as a primary diagnostic tool in hospital associated patients. The high percentage of HEV IgG seropositivity confirms earlier epidemiological studies.     

Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal

Background

Infection with the hepatitis E virus (HEV) can cause acute hepatitis in endemic areas in immune-competent hosts, as well as chronic infection in immune-compromised subjects in non-endemic areas. Most studies assessing HEV infection in HIV-infected populations have been performed in developed countries that are usually affected by HEV genotype 3. The objective of this study is to measure the prevalence and risk of acquiring HEV among HIV-infected individuals in Nepal.

Methods

We prospectively evaluated 459 Human Immunodeficiency Virus (HIV)-positive individuals from Nepal, an endemic country for HEV, for seroprevalence of HEV and assessed risk factors associated with HEV infection. All individuals were on antiretroviral therapy and healthy blood donors were used as controls.

Results

We found a high prevalence of HEV IgG (39.4%) and HEV IgM (15.3%) in HIV-positive subjects when compared to healthy HIV-negative controls: 9.5% and 4.4%, respectively (OR: 6.17, 95% CI 4.42–8.61, p?<?0.001 and OR: 3.7, 95% CI 2.35–5.92, p?<?0.001, respectively). Individuals residing in the Kathmandu area showed a significantly higher HEV IgG seroprevalance compared to individuals residing outside of Kathmandu (76.8% vs 11.1%, OR: 30.33, 95% CI 18.02–51.04, p?=?0.001). Mean CD4 counts, HIV viral load and presence of hepatitis B surface antigen correlated with higher HEV IgM rate, while presence of hepatitis C antibody correlated with higher rate of HEV IgG in serum. Overall, individuals with HEV IgM positivity had higher levels of alanine aminotransferase (ALT) than IgM negative subjects, suggesting active acute infection. However, no specific symptoms for hepatitis were identified.

Conclusions

HIV-positive subjects living in Kathmandu are at higher risk of acquiring HEV infection as compared to the general population and to HIV-positive subjects living outside Kathmandu.

     

Prevalence and Trend of Major Transfusion-Transmissible Infections among Blood Donors in Western China, 2005 through 2010

BackgroundThe prevalence of transfusion-transmissible infections (TTIs) in blood donations is important for evaluating blood safety and potential risks to the population. This study investigated the prevalence of TTIs among blood donors in Western China and suggested measures for policy-makers.MethodsThe screening results of 66,311 donations between 2005 and 2010 from a central blood center in Western China were analyzed. The prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis infections were expressed in percentages for the entire study group as well as groups by demographic characteristics and donation frequency, with differences analyzed using Fisher''s exact or Chi-square test. Logistic regression was performed to identify the influencing factors of the detected results.Results1,769 (2.67%, 95% CI 2.55–2.79%) of the donated blood had serological evidence of infection with at least one pathogen and 44 (0.07%, 95% CI 0.05–0.09%) showed evidence of multiple infections. The seroprevalence of HBV, HCV, HIV, and syphilis infections was 0.87% (95% CI 0.80–0.94%), 0.86% (95% CI 0.79–0.93%), 0.31% (95% CI 0.26–0.35%), and 0.70% (95% CI 0.64–0.76%) respectively. Trend analysis for the prevalence of TTIs showed a significant increase from 2.44% to 3.71% (χ² = 100.72, p = 0.00) over this 6-year period. The positive rates for TTIs varied along demographic lines. The top three risk factors in test-positive donors were identified as age, education level and donation frequency. The older age group and lower educated group were linked to a higher prevalence of TTIs. A decreasing prevalence was associated with an increasing frequency of blood donations (χ2 = 562.78, p = 0.00).ConclusionsHepatitis B and C were found most, and often in conjunction with syphilis. These were the primary threats to blood safety. The high positivity rate and the increasing prevalence of TTIs among blood donors in Western China call for further actions.     

Hepatitis E virus seroprevalence among blood donors in southwest Switzerland

Aim

The aim of this study was to determine the seroprevalence of Hepatitis E virus (HEV) among blood donors in southwest Switzerland.

Background

HEV is recognized as a food-borne disease in industrialized countries, transmitted mainly through pork meat. Cases of transmission through blood transfusion have also been reported. Recent studies have revealed seroprevalence rates of 13.5%, 16.6% and 20.6% among blood donors in England, France and Denmark, respectively.

Methods

We analyzed 550 consecutive blood donor samples collected in the region of Lausanne, canton of Vaud, Switzerland, for the presence of anti-HEV IgG, using the MP Diagnostics HEV ELISA kit. For each donor, we documented age, sex and alanine aminotransferase (ALT) value.

Results

The study panel was composed of 332 men (60.4%) and 218 women (39.6%). Overall, anti-HEV IgG was found in 27 of 550 samples (4.9%). The seroprevalence was 5.4% (18/332) in men and 4.1% (9/218) in women. The presence of anti-HEV IgG was not correlated with age, gender or ALT values. However, we observed a peak in seroprevalence of 5.3% in individuals aged 51 to 70 years old.

Conclusions

Compared with other European countries, HEV seroprevalence among blood donors in southwest Switzerland is low. The low seroprevalence may be explained by the sensitivity of commercial tests used and/or the strict regulation of animal and meat imports. Data regarding HEV prevalence in Swiss livestock are lacking and merit exploration.     

Efficacy of Neonatal HBV Vaccination on Liver Cancer and Other Liver Diseases over 30-Year Follow-up of the Qidong Hepatitis B Intervention Study: A Cluster Randomized Controlled Trial

Background

Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined.

Methods and Findings

The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10–14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996–2000 and 2008–2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%–97%), 70% (95% CI 15%–89%), and 69% (95% CI 34%–85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%–30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%–75%). Receiving a booster at age 10–14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR] = 0.68, 95% CI 0.47–0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up.

Conclusions

Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors'' Summary     

Diagnostic accuracy of cervical cancer screening and screening–triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study

BackgroundCervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen–triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa.Methods and findingsWLHIV aged 25–50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol’s iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%–52.7%) and CIN3+ (56.1%, 95% CI 43.3%–68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%–81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%–93.2%) for CIN2+ and 86.4% (95% CI 75.7%–93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%–58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%–76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%–86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28–2.32; CIN3+: 1.18, 95% CI 0.94–1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%–77.9%; CIN3+: 80.8%, 95% CI 67.5%–90.4%) and specificity (81.6%, 95% CI 77.6%–85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%–91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%–47.1%; relative specificity = 0.57, 95% CI 0.52–0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%–3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%–3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%–1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today.ConclusionsIn this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.

In this cohort study, Helen Kelly and colleagues explore cervical cancer screening strategies for women living with HIV.     

Declining prevalence of hepatitis A virus antibodies among children from low socioeconomic groups reinforces the need for the implementation of hepatitis A vaccination in Brazil

Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.