Preeyaporn Vichaiwattana

Molecular epidemiological study of hepatitis B virus among migrant workers from Cambodia, Laos, and Myanmar to Thailand.

Although hepatitis B virus (HBV) infection is endemic in Southeast Asia, molecular epidemiological data on HBV circulating in some countries are limited. The aims of this study were to evaluate the seroprevalence of HBV and its genetic variability among migrant workers from Cambodia, Laos, and Myanmar in Thailand. Sera collected from 1,119 Cambodian, 787 Laotian, and 1,103 Myanmarese workers were tested for HBsAg. HBV DNA was amplified and the pre‐S/S region was sequenced for genotyping and genetic mutation analysis. HBsAg was detected in 282 (9.4%). The prevalence of HBsAg among migrant workers from Cambodia, Laos, and Myanmar was 10.8%, 6.9%, and 9.7%, respectively. Of 224 subjects positive for HBV DNA, 86% were classified as genotype C (99% were sub‐genotype C1) and 11.6% were genotype B (30.8%, 34.6%, and 30.8% were sub‐genotypes B2, B3, and B4, respectively). Various point mutations in the “a” determinant region were detected in approximately 18% of these samples, of which Ile126Ser/Asn was the most frequent variant. Sequencing analysis showed that 19.1% of samples had pre‐S mutations, with pre‐S2 deletion as the most common mutant (7.7%) followed by pre‐S2 start codon mutation (3.8%) and both pre‐S2 deletion and start codon mutation (3.3%). High prevalence of HBV infection (approximately 7–11%) was found among migrant workers from Cambodia, Laos, and Myanmar, which may reflect the current seroprevalence in their respective countries. The data also demonstrated that HBV sub‐genotype C1 was the predominant strain and various mutations of HBV occurring naturally were not uncommon among these populations. J. Med. Virol. 82:1341–1349, 2010.

The Success of a Universal Hepatitis B Immunization Program as Part of Thailand's EPI after 22 Years' Implementation.

Hepatitis B vaccination for newborns was introduced in two provinces in 1988 as part of Thailand’s Expanded Program on Immunization (EPI), and extended to the whole country in 1992. Our previous studies showed that children and adolescents who were born after the implementation of this program had a carrier rate of less than 1%, compared with 5–6% before implementation. In 2014 we performed hepatitis B serosurveys among 5964 subjects in the different geographic regions of the country to evaluate the long-term immunogenicity and impact of universal hepatitis B vaccination in newborns as part of the 22-year EPI program, by assessing HBsAg, anti-HBc and anti-HBs seropositivity status. The number of HB virus (HBV) carriers, both children and young adults, who were born after universal HB vaccination was markedly reduced. The carrier rates among the age groups 6 months to 5 years, 5–10, 11–20, 21–30, 31–40, 41–50 and >50 years were respectively 0.1, 0.29, 0.69, 3.12, 3.78, 4.67 and 5.99%. The seropositivity rate for HBsAg in the post-EPI group was 0.6%, whereas in the pre-EPI group it was as high as 4.5% (p<0.001). HBV infection by means of detectable anti-HBc had also drastically declined in the population born after the HB vaccine was integrated into the EPI program. We estimated that the total number of HBV carriers amounted to 2.22 million, or 3.48% of the total population, most of whom are adults. The HB vaccine is the first vaccine shown to be effective in preventing the occurrence of chronic liver disease and hepatocellular carcinoma. Universal vaccination campaign will contribute to the eventual eradication of HBV-associated disease.

Decreasing Hepatitis C Virus Infection in Thailand in the Past Decade: Evidence from the 2014 National Survey

Hepatitis C virus (HCV) infection affects ≥ 180 million individuals worldwide especially those living in developing countries. Recent advances in direct-acting therapeutics promise effective treatments for chronic HCV carriers, but only if the affected individuals are identified. Good treatment coverage therefore requires accurate epidemiological data on HCV infection. In 2014, we determined the current prevalence of HCV in Thailand to assess whether over the past decade the significant number of chronic carriers had changed. In total, 5964 serum samples from Thai residents between 6 months and 71 years of age were obtained from 7 provinces representing all 4 geographical regions of Thailand and screened for the anti-HCV antibody. Positive samples were further analyzed using RT-PCR, sequencing, and phylogenetic analysis to identify the prevailing HCV genotypes. We found that 56 (0.94%) samples tested positive for anti-HCV antibody (mean age = 36.6±17.6 years), while HCV RNA of the core and NS5B subgenomic regions was detected in 23 (41%) and 19 (34%) of the samples, respectively. The seropositive rates appeared to increase with age and peaked in individuals 41–50 years old. These results suggested that approximately 759,000 individuals are currently anti-HCV-positive and that 357,000 individuals have viremic HCV infection. These numbers represent a significant decline in the prevalence of HCV infection. Interestingly, the frequency of genotype 6 variants increased from 8.9% to 34.8%, while the prevalence of genotype 1b declined from 27% to 13%. These most recent comprehensive estimates of HCV burden in Thailand are valuable towards evidence-based treatment coverage for specific population groups, appropriate allocation of resources, and improvement in the national public health policy.

Epidemiology of seasonal influenza in Bangkok between 2009 and 2012.

INTRODUCTION This study investigated influenza activity in Bangkok, Thailand between June 2009 and July 2012. METHODOLOGY Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to detect influenza viruses among patients with influenza-like illnesses. RESULTS Of the 6417 patients tested, influenza virus infection was detected in 42% (n = 2697) of the specimens. Influenza A pH1N1 viruses comprised the predominant strain between 2009 and 2010, and seasonal influenza (H3) had a high prevalence in 2011. Laboratory data showed a prevalence and seasonal pattern of influenza viruses. In 2009, influenza activity peaked in July, the rainy season. In 2010, influenza activity happened in two phases, with the initial one at the beginning of the year and another peak between June and August 2010, which again corresponded to the rainy period. Influenza activity was low for several consecutive weeks at the beginning of 2011, and high H3N2 activity was recorded during the rainy season between July and September 2011. However, from the beginning of 2012 through July 2012, pH1N1, influenza H3N2, and influenza B viruses continuously circulated at a very low level. CONCLUSION The seasonal pattern of influenza activity in Thailand tended to peak during rainy season between July and September.

Seroprevalence of Antibodies to Pertussis Toxin among Different Age Groups in Thailand after 37 Years of Universal Whole-Cell Pertussis Vaccination

Despite the high coverage of prophylactic vaccine against Bordetella pertussis infection in many countries for more than three decades, pertussis remains a common vaccine-preventable disease. Infections have been detected more commonly in countries using acellular pertussis vaccine in their Expanded Program of Immunization. Thailand implemented a routine infant immunization program with whole-cell pertussis vaccine in 1977, and since 1992, the national vaccine policy has offered a five-dose whole-cell pertussis vaccine for children given at the ages of 2, 4, 6, 18, and 48 months. This study aimed to investigate the seroprevalence of antibodies to pertussis toxin among healthy people across all ages to determine the level of whole-cell vaccine-induced immunity in the population, and to identify which age group should be targeted for a booster dose. The lowest seronegative rate and highest geometric mean concentrations were found in the 0–10 years age group, corresponding to their recent pertussis vaccination. The proportion of people with undetectable IgG level was prominent, starting after 11 years of age onwards. Now that a reduced-dose pertussis vaccine with fewer adverse effects is available, a booster dose during adolescence should be considered in order to reduce the incidence of pertussis disease. Further studies exploring how long the reduced-dose pertussis vaccine can provide protective immunity against pertussis disease when administered to adults and adolescents should also be performed.

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.

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.

Assessment of hepatitis C virus infection in two adjacent Thai provinces with drastically different seroprevalence

Improved awareness of the hepatitis C virus (HCV) transmission has contributed to the overall decline in the HCV infection rate in some developing countries including Thailand. Chronic HCV infection in some rural Thai communities, however, presents a challenge in the efforts to treat and manage HCV-related diseases. Published and unpublished studies have suggested an unusually high incidence of HCV infection in a Thai province of Phetchabun compared to elsewhere in Thailand. To determine the magnitude of HCV infection and identify potential factors contributing to the higher rate of HCV infection in this province, we performed a population-based study in Phetchabun (n = 1667) and the neighboring Khon Kaen province (n = 1410) where HCV prevalence is much lower. Individuals between 30 and 64 years old completed detailed questionnaires designed to identify HCV risk factors and provided blood samples for anti-HCV antibody screening. The anti-HCV seropositive rates were 15.5% (259/1667) in Phetchabun and 3.6% (51/1410) in Khon Kaen. Positive samples were subsequently genotyped for HCV core gene sequence and assessed for the hepatitis B virus surface antigen (HBsAg) and human immunodeficiency virus antigen/antibody (HIV Ag/Ab). More individuals in Phetchabun possessed the combined presence of HBsAg (5.0%) and HIV Ag/Ab (0.4%) than those in Khon Kaen (3.9% HBsAg and 0.0% HIV Ag/Ab). While male gender, intravenous drug use (IVDU) and tattoos were significant HCV risk factors in both provinces (p <0.05), education less than high school and agriculture-related occupation were additionally associated with HCV in Phetchabun. HCV genotypes 6, 3, and 1 were identified in similar frequency in both provinces. We estimated that prevalence of HCV seropositivity and viremic carriers were higher in Phetchabun (143 and 111 per 1000) than in Khon Kaen (34 and 22 per 1000). Finally, we derived a simple risk factor-based scoring system as a useful preclinical tool to screen individuals at risk of chronic HCV infection prior to intervention. Knowledge gained from this study will assist in HCV screening and promote access to anti-viral treatment in high-risk groups.

Liver disease burden and required treatment expenditures for hepatitis C virus (HCV) infection in Thailand: Implications for HCV elimination in the new therapeutic era, a population-based study

The prevalence of hepatitis C virus (HCV) infection has been decreasing globally, but the growing effects of HCV-related morbidity and mortality remain of concern. Advances in curative medicine, involving direct-acting antivirals (DAAs), have led many countries to aim to eradicate HCV. Information on epidemiology and disease burden is essential for national policy development. Thus, this study aimed to determine the HCV-related hepatic disease burden in areas of Thailand with high and average HCV prevalence in order to extrapolate the viral burden across Thailand. Patients previously diagnosed as positive for anti-HCV antibodies were recruited to assess chronic HCV infection (CHC) status, liver function, HCV-RNA level and hepatic fibrosis. The number of patients eligible for Universal Health Coverage (UC) scheme and the approximately required expenditure on interferon (IFN)-based treatment were estimated. In areas of both high (12%) and average (2%) HCV viremic prevalence, over half of the patients (52.2% to 62.5%) had advanced liver fibrosis (F3 and F4). A striking percentage of patients with F4 (38.9%) were found in the high-prevalence area, while comparable proportions of advanced liver fibrosis presented in the two areas and disease burden peaked at 50–59 years. Under the current UC program treatment scenario, 78–83% of CHC patients with stage F2–F4 fibrosis were eligible for treatment. The estimated expenditure required for overall CHC treatment across the whole country was 1,240 million USD at this current status, but the declining cost of generic DAA-based therapy may reduce the requirement to <90 million USD. This study provides information on the estimated number of CHC patients, liver disease burden and expenditure requirements for Thailand. To eliminate HCV by 2030, proactive government strategies raising public health to minimize transmission and emphasizing targeted screen-and-treatment programs, novel therapeutic guideline development for decentralizing treatment, and effective budget allocation are urgently needed.

HCV core antigen is an alternative marker to HCV RNA for evaluating active HCV infection: implications for improved diagnostic option in an era of affordable DAAs

The core antigen of the hepatitis C virus (HCV Ag) presents an alternative marker to HCV RNA when screening patients for HCV viremia. This study sought to evaluate the utility of HCV Ag as a marker to assess active HCV infection in individuals residing in an HCV-endemic area. From 298 HCV-seropositive individuals evaluated for the presence of anti-HCV antibody, HCV Ag and HCV RNA, anti-HCV antibody was detected in 252 individuals (signal-to-cutoff ratios ≥5), HCV RNA was detected in 222 individuals (88%), and HCV Ag was reactive (≥3 fmol/L) in 220 individuals (87%). HCV genotype 1, 3, and 6 were identified. HCV Ag significantly correlated with HCV RNA irrespective of HCV genotype and/or HBV co-infection (log HCV RNA = 2.67 + 0.95 [log HCV Ag], R2 = 0.890, p < 0.001). To predict HCV viremia (HCV Ag ≥ 3 fmol/L), the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 99%, 99%, 100%, 100% and 97%, respectively. We concluded that HCV Ag was a good surrogate marker for HCV RNA and could be used to diagnose active HCV infection in a resource-limited setting. As a result, a cost-effective strategy for screening and identifying active HCV carriers using HCV Ag detection would enable more patients access to efficacious and increasingly affordable direct-acting antivirals (DAAs) for the treatment of HCV infection.