Risk Factors for Severe Enteroviral Infections in Children.

OBJECTIVE: To study the risk factors associated with severe enterovirus infection among hospitalized pediatric patients with hand, foot, and mouth disease (HFMD) at King Narai Hospital, Lopburi, Thailand. MATERIAL AND METHOD: We reviewed all of the suspected enterovirus infection cases aged less than 15 years admitted to King Narai Hospital between 2011 and 2013. Cases were classified into mild and severe enterovirus infection. Risk factors for severe enterovirus infection were analyzed using univariate and multivariate logistic regressions. RESULTS: During the study period, 156 patients met the case definition for further analysis. Of those 156 patients, 131 (84.0%) were classifed as mild cases, and 25 (16.0%) as severe cases with five (3.2%) deaths. The most common manifestations among the severe cases were seizures, pneumonia, meningoencephalitis, meningitis, and hyperglycemia. Of the 31 identifiable cases, 12 were caused by enterovirus 71 (EV71), 12 by coxsackievirus A16 (CA16), four by both, and three by other enterovirus. The clinical manifestations that were significantly related to severe enterovirus infection in univariate analysis were age of less than one year, highest body temperature greater than 39.0 degrees C, duration of fever greater than three days, absence of skin lesions, diarrhea, dyspnea, and hyperglycemia. The clinical manifestations that were significantly related to severe enterovirus infection by both univariate and multivariate analyses were absence of oral lesions, seizures, and drowsiness/lethargy. CONCLUSION: The major pathogens of severe disease were EV71 and CA16. High-risk factors significantly related to severe enterovirus infection in both univariate and multivariate analyses were absence of oral lesions, seizures, and drowsiness/lethargy. Early recognition of children at risk and prompt treatment is important to mitigate the deterioration of patients with enterovirus infection.

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

[This corrects the article DOI: 10.1371/journal.pone.0149362.].

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.

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.

RISK FACTORS FOR SEVERE HAND, FOOT AND MOUTH DISEASE.

We studied risk factors associated with severe hand, foot and mouth disease (HFMD) caused by enteroviruses among patients aged less than 15 years admitted to King Narai Hospital, Lopburi, Thailand during 2011-2013. Cases were divided into either mild or severe. Severe cases were those with encephalitis, meningitis, myocarditis, pneumonia, pulmonary edema or respiratory failure. Risk factors for severe infection were evaluated using univariate and multivariate logistic regression analysis. One hundred eighteen patients met the case definition of HFMD. Of these, 95 (80.5%) were classified as mild cases, and 23 (19.5%) as severe cases; there were 5 deaths (4.2%). Of the 23 severe cases, 9 were infected with coxsackievirus A16 (CA16), 8 with enterovirus 71 (EV71) and 4 with both EV71 and CA16. The most common presentations among the severe caseswere: seizures (74%), pneumonia (39%), encephalitis (39%), and meningitis (13%). The clinical manifestations significantly related to severe HFMD on univariate analysis were highest body temperature 39.00C, duration of fever 23 days, absence of skin lesions, diarrhea, dyspnea, seizures and hyperglycemia. The clinical manifestations significantly related to severe HFMD on both univariate and multivariate analyses were age less than 1 year, absence of oral lesions and drowsiness/lethargy. Clinicians should be aware of these factors. Early recognition of severe cases is important to increase the rates of successful outcomes and reduce mortality.

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.

Measles-mumps-rubella vaccination induced thrombocytopenia: a case report and review of the literature.

Immune thrombocytopenia (ITP) is a disease with autoimmune destruction of platelets. ITP among children has been associated with viral infections and some vaccinations. We report a case of ITP after measles-mumps-rubella (MMR) vaccination in a 10-month-old male infant who presented with purpura and acute gastrointestinal bleeding. This case was successfully treated with corticosteroids and intravenous immunoglobulin. ITP is a rare complication of the MMR vaccine that physicians should be aware of.