Correction: Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children.

[This corrects the article DOI: 10.1371/journal.pntd.0005621.].

Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children.

BACKGROUND: Indonesia reports the second highest dengue disease burden in the world; these data are from passive surveillance reports and are likely to be significant underestimates. Age-stratified seroprevalence data are relatively unbiased indicators of past exposure and allow understanding of transmission dynamics. METHODOLOGY/PRINCIPAL FINDINGS: To better understand dengue infection history and associated risk factors in Indonesia, a representative population-based cross-sectional dengue seroprevalence study was conducted in 1-18-year-old urban children. From October to November 2014, 3,210 children were enrolled from 30 geographically dispersed clusters. Serum samples were tested for anti-dengue IgG antibodies by indirect ELISA. A questionnaire investigated associations between dengue serologic status and household socio-demographic and behavioural factors. Overall, 3,194 samples were tested, giving an adjusted national seroprevalence in this urban population of 69.4% [95% CI: 64.4-74.3] (33.8% [95% CI: 26.4-41.2] in the 1-4-year-olds, 65.4% [95% CI: 69.1-71.7] in the 5-9-year-olds, 83.1% [95% CI: 77.1-89.0] in the 10-14-year-olds, and 89.0% [95% CI: 83.9-94.1] in the 15-18-year-olds). The median age of seroconversion estimated through a linear model was 4.8 years. Using a catalytic model and considering a constant force of infection we estimated 13.1% of children experience a primary infection per year. Through a hierarchical logistic multivariate model, the subject's age group (1-4 vs 5-9 OR = 4.25; 1-4 vs. 10-14 OR = 12.60; and 1-4 vs 15-18 OR = 21.87; p<0.0001) and the number of cases diagnosed in the household since the subject was born (p = 0.0004) remained associated with dengue serological status. CONCLUSIONS/SIGNIFICANCE: This is the first dengue seroprevalence study in Indonesia that is targeting a representative sample of the urban paediatric population. This study revealed that more than 80% of children aged 10 years or over have experienced dengue infection at least once. Prospective incidence studies would likely reveal dengue burdens far in excess of reported incidence rates.

Influenza and pregnancy: a review of the literature from India.

Maternal influenza infection is known to cause substantial morbidity and mortality among pregnant women and young children. Many professional healthcare bodies including the World Health Organization (WHO) have identified pregnant women as a priority risk group for receipt of inactivated seasonal influenza vaccination. However influenza prevention in this group is not yet a public health priority in India. This literature review was undertaken to examine the Indian studies of influenza among pregnant women. Eight Indian studies describing influenza burden and/or outcomes among pregnant women with influenza were identified. In most studies, influenza A (pH1N1) was associated with increased maternal mortality (25-75%), greater disease severity, and adverse fetal outcomes as compared to nonpregnant women. Surveillance for seasonal influenza infections along with higher quality prospective studies among pregnant women is needed to quantify disease burden, improve awareness among antenatal care providers, and formulate antenatal influenza vaccine policies.

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis.

BACKGROUND: The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. METHODS: We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. FINDINGS: We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. INTERPRETATION: Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. FUNDING: WHO; Bill & Melinda Gates Foundation.

A method for estimating vaccine-preventable pediatric influenza pneumonia hospitalizations in developing countries: Thailand as a case study.

The burden of influenza in children is increasingly appreciated; some middle-income countries are considering support for influenza vaccine programs. To support decision-making, methods to estimate the potential impact of proposed programs are needed. Using Thailand as a case-study, we present a model that uses surveillance data, published vaccine effectiveness estimates, and vaccination coverage assumptions to estimate the impact of influenza vaccination on pediatric influenza pneumonia hospitalizations. Approximately 56,000 influenza pneumonia hospitalizations occur annually among children aged <18 years in Thailand; 23,700 (41%) may be vaccine-preventable. Vaccination of 85% of Thai children aged 7 months-4 years might prevent 30% of all pediatric influenza pneumonia hospitalizations in Thailand.

Influenza virus contamination of common household surfaces during the 2009 influenza A (H1N1) pandemic in Bangkok, Thailand: implications for contact transmission.

BACKGROUND: Rational infection control guidance requires an improved understanding of influenza transmission. We studied households with an influenza-infected child to measure the prevalence of influenza contamination, the effect of hand washing, and associations with humidity and temperature. METHODOLOGY: We identified children with influenza and randomly assigned their households to hand washing and control arms. Six common household surfaces and the fingertips of the index patient and symptomatic family members were swabbed. Specimens were tested by real-time reverse-transcription polymerase chain reaction (rRT-PCR), and specimens with positive results were placed on cell culture. A handheld psychrometer measured meteorological data. RESULTS: Sixteen (17.8%) of 90 households had influenza A-positive surfaces by rRT-PCR, but no viruses could be cultured. The fingertips of 15 (16.6%) of the index patients had results positive for influenza A, and 1 virus was cultured. Index patients with seasonal influenza infections shed more virus than did patients with pandemic influenza infection. Control households had a higher prevalence of surface contamination (11 [24.4%] of 45) than did hand washing households (5 [11.1%] of 45); prevalence risk difference (PRD), 13.3%; [95% confidence interval {CI}, −2.2% to 28.9%]; P = .09). Households in which the age of the index patient was ≤8 years had a significantly higher prevalence of contamination (PRD ,19.1%; 95% CI, 5.3% -32.9%; P = .02). Within the strata of households with secondary infections, an effect of lower absolute humidity is suggested (P = .07). CONCLUSIONS: We documented influenza virus RNA contamination on household surfaces and on the fingertips of ill children. Homes with younger children were more likely than homes of older children to have contaminated surfaces. Lower absolute humidity favors surface contamination in households with multiple infections. Increased hand washing can reduce influenza contamination in the home.

Incidence, seasonality and mortality associated with influenza pneumonia in Thailand: 2005-2008.

BACKGROUND: Data on the incidence, seasonality and mortality associated with influenza in subtropical low and middle income countries are limited. Prospective data from multiple years are needed to develop vaccine policy and treatment guidelines, and improve pandemic preparedness. METHODS: During January 2005 through December 2008, we used an active, population-based surveillance system to prospectively identify hospitalized pneumonia cases with influenza confirmed by reverse transcriptase-polymerase chain reaction or cell culture in 20 hospitals in two provinces in Thailand. Age-specific incidence was calculated and extrapolated to estimate national annual influenza pneumonia hospital admissions and in-hospital deaths. RESULTS: Influenza was identified in 1,346 (10.4%) of pneumonia patients of all ages, and 10 influenza pneumonia patients died while in the hospital. 702 (52%) influenza pneumonia patients were less than 15 years of age. The average annual incidence of influenza pneumonia was greatest in children less than 5 years of age (236 per 100,000) and in those age 75 or older (375 per 100,000). During 2005, 2006 and 2008 influenza A virus detection among pneumonia cases peaked during June through October. In 2007 a sharp increase was observed during the months of January through April. Influenza B virus infections did not demonstrate a consistent seasonal pattern. Influenza pneumonia incidence was high in 2005, a year when influenza A(H3N2) subtype virus strains predominated, low in 2006 when A(H1N1) viruses were more common, moderate in 2007 when H3N2 and influenza B co-predominated, and high again in 2008 when influenza B viruses were most common. During 2005-2008, influenza pneumonia resulted in an estimated annual average 36,413 hospital admissions and 322 in-hospital pneumonia deaths in Thailand. CONCLUSION: Influenza virus infection is an important cause of hospitalized pneumonia in Thailand. Young children and the elderly are most affected and in-hospital deaths are more common than previously appreciated. Influenza occurs year-round and tends to follow a bimodal seasonal pattern with substantial variability. The disease burden varies significantly from year to year. Our findings support a recent Thailand Ministry of Public Health (MOPH) decision to extend annual influenza vaccination to older adults and suggest that children should also be targeted for routine vaccination.

Severe human influenza infections in Thailand: oseltamivir treatment and risk factors for fatal outcome.

BACKGROUND: Influenza is often not recognized as an important cause of severe or fatal disease in tropical and subtropical countries in Southeast Asia. The extent to which Oseltamivir treatment may protect against a fatal outcome in severe influenza infections is not known. Thailand's National Avian Influenza Surveillance (NAIS) system affords a unique opportunity to describe the epidemiology of laboratory-confirmed severe and fatal human influenza infections. METHODOLOGY/PRINCIPAL FINDINGS: During January 2004 through December 2006, 11,641 notifications to the NAIS were investigated in 73 of 76 Thai provinces. Clinical and demographic data and respiratory swab specimens were collected and tested by PCR for influenza. Using the NAIS database, we identified all patients with laboratory confirmed human influenza (A/H3N2, A/H1N1 and Type B) infection. A retrospective medical record review was conducted on all fatal cases with laboratory confirmed influenza and from a sample of hospitalized cases in 28 provinces. The association of underlying risk factors, Oseltamivir treatment and risk of a fatal outcome were examined. Human influenza infections were identified in 2,075 (18%) cases. Twenty-two (1%) deaths occurred including seven deaths in children less than ten years of age. Thirty-five percent of hospitalized human influenza infections had chest X-ray confirmed pneumonia. Current or former smoking; advanced age, hypertension and underlying cardiovascular, pulmonary or endocrine disease were associated with a fatal outcome from human influenza infection. Treatment with Oseltamivir was statistically associated with survival with a crude OR of .11 (95% CI: 0.04-0.30) and .13 (95% CI: 0.04-0.40) after controlling for age. CONCLUSIONS: Severe and fatal human influenza infections were commonly identified in the NAIS designed to identify avian A/H5N1 cases. Treatment with Oseltamivir is associated with survival in hospitalized human influenza pneumonia patients.

Field performance and new uses of rapid influenza testing in Thailand.

OBJECTIVES: Rapid influenza tests are increasingly used in surveillance systems and for clinical care in Southeast Asia. However, the performance and utility of rapid influenza tests under field conditions in rural Southeast Asia has not been evaluated. METHODS: In the context of a larger study on the causes of respiratory illness in rural Thailand, we used a rapid test to collect data on influenza burden, seasonality, and cost of illness. We compared the performance of the QuickVue Influenza Test to tissue cell viral culture and reverse transcriptase-polymerase chain reaction (RT-PCR) among 1092 Thai patients meeting the World Health Organization case definition for influenza-like illness over a 12-month period. RESULTS: The sensitivity and specificity of the QuickVue test compared to viral culture were 77% and 96%, respectively. Rapid influenza tests were useful to describe the seasonality of influenza, estimate the cost of illness, increase the sensitivity of surveillance, conduct outbreak responses, and guide evaluation of suspected avian influenza virus infections. CONCLUSIONS: Despite their high cost, rapid influenza diagnostic tests are useful tools for influenza research, surveillance, and outbreak investigations in Southeast Asia.

The cost of influenza in Thailand.

The cost of influenza in less wealthy tropical countries is needed to inform national vaccine policy decisions. Between September 2003 and August 2004, we prospectively identified hospitalized pneumonia cases and outpatients with laboratory confirmed influenza in a Thai province. Disease incidence, patient interviews, medical record reviews, and data from a national health survey were used to calculate direct and indirect costs which were extrapolated to the Thai population. Influenza was identified in 80 (11%) of 761 hospitalized pneumonia inpatients with projected annual incidence of 18-111/100,000 population. Influenza was confirmed in 23% of 1092 outpatients with an estimated annual incidence of 1420/100,000 population. Influenza was estimated to cause between US dollar 23.4 and US dollar 62.9 million in economic losses with lost productivity accounting for 56% of all costs. The burden of influenza in Thailand is greater than previously appreciated, particularly in young children and the elderly. The impact and cost-effectiveness of influenza vaccination for high-risk groups merits further investigation.

Influenza in Thailand: a case study for middle income countries.

Recent studies in Hong Kong and Singapore suggest that the annual impact of influenza in these wealthy tropical cities may be substantial, but little is known about the burden in middle-income tropical countries. We reviewed the status of influenza surveillance, vaccination, research, and policy in Thailand as of January 2004. From 1993 to 2002, 64-91 cases of clinically diagnosed influenza were reported per 100,000 persons per year. Influenza viruses were isolated in 34% of 4305 specimens submitted to the national influenza laboratory. Vaccine distribution figures suggest that less than 1% of the population is immunized against influenza each year. In January 2004, Thailand reported its first documented outbreak of influenza A H5N1 infection in poultry and the country's first human cases of avian influenza. Thailand's growing economy, well-developed public health infrastructure, and effective national immunization program could enable the country to take more active steps towards influenza control.

Advances DNA vaccines.

Extraordinary advances in biotechnology make DNA vaccines the most promising area of vaccinology. This article reviews the public health impact of vaccines in the 20th century, summarizes immunologic concepts, and updates the status of DNA vaccine development and its impact on clinical practice.