INTRODUCTION: While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei "aerosols" in transmission is controversial. METHODS AND FINDINGS: In Hong Kong and Bangkok, in 2008-11, subjects were recruited from outpatient clinics if they had recent onset of acute respiratory illness and none of their household contacts were ill. Following a positive rapid influenza diagnostic test result, subjects were randomly allocated to one of three household-based interventions: hand hygiene, hand hygiene plus face masks, and a control group. Index cases plus their household contacts were followed for 7-10 days to identify secondary infections by reverse transcription polymerase chain reaction (RT-PCR) testing of respiratory specimens. Index cases with RT-PCR-confirmed influenza B were included in the present analyses. We used a mathematical model to make inferences on the modes of transmission, facilitated by apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We estimated that approximately 37% and 26% of influenza B virus transmission was via the aerosol mode in households in Hong Kong and Bangkok, respectively. In the fitted model, influenza B virus infections were associated with a 56%-72% risk of fever plus cough if infected via aerosol route, and a 23%-31% risk of fever plus cough if infected via the other two modes of transmission. CONCLUSIONS: Aerosol transmission may be an important mode of spread of influenza B virus. The point estimates of aerosol transmission were slightly lower for influenza B virus compared to previously published estimates for influenza A virus in both Hong Kong and Bangkok. Caution should be taken in interpreting these findings because of the multiple assumptions inherent in the model, including that there is limited biological evidence to date supporting a difference in the clinical features of influenza B virus infection by different modes.

Within a hand-washing clinical trial, we evaluated factors associated with fomite contamination in households with an influenza-infected child. Influenza virus RNA contamination was higher in households with low absolute humidity and in control households, suggesting that hand washing reduces surface contamination.

The serial interval (SI) of human influenza virus infections is often described by a single distribution. Understanding sources of variation in the SI could provide valuable information for understanding influenza transmission dynamics. Using data from a randomized household study of nonpharmaceutical interventions to prevent influenza transmission in Bangkok, Thailand, over 34 months between 2008 and 2011, we estimated the influence of influenza virus type/subtype and other characteristics of 251 pediatric index cases and their 315 infected household contacts on estimates of household SI. The mean SI for all households was 3.3 days. Relative to influenza A(H1N1)pdm09 (3.1 days), the SI for influenza B (3.7 days) was 22% longer (95% confidence interval: 4, 43), or about half a day. The SIs for influenza viruses A(H1N1) and A(H3N2) were similar to that for A(H1N1)pdm09. SIs were shortest for older index cases (age 11-14 years) and for younger infected household contacts (age ≤15 years). Greater time spent in proximity to the index child was associated with shorter SIs. Differences in the SI might reflect differences in incubation period, viral shedding, contact, or susceptibility. These findings could improve parameterization of mathematical models to better predict the impact of epidemic or pandemic influenza mitigation strategies.

BACKGROUND: Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009-2010. METHODS: We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1:2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. RESULTS: Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). CONCLUSIONS: Influenza-associated hospitalization rates in Thailand during 2009-10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children.

BACKGROUND: Evidence is needed on the effectiveness of non-pharmaceutical interventions (NPIs) to reduce influenza transmission. METHODOLOGY: We studied NPIs in households with a febrile, influenza-positive child. Households were randomized to control, hand washing (HW), or hand washing plus paper surgical face masks (HW + FM) arms. Study nurses conducted home visits within 24 hours of enrollment and on days 3, 7, and 21. Respiratory swabs and serum were collected from all household members and tested for influenza by RT-PCR or serology. PRINCIPAL FINDINGS: Between April 2008 and August 2009, 991 (16.5%) of 5995 pediatric influenza-like illness patients tested influenza positive. Four hundred and forty-two index children with 1147 household members were enrolled, and 221 (50.0%) were aged <6 years. Three hundred and ninety-seven (89.8%) households reported that the index patient slept in the parents' bedroom. The secondary attack rate was 21.5%, and 56/345 (16.3%; 95% CI 12.4-20.2%) secondary cases were asymptomatic. Hand-washing subjects reported 4.7 washing episodes/day, compared to 4.9 times/day in the HW + FM arm and 3.9 times/day in controls (P = 0.001). The odds ratios (ORs) for secondary influenza infection were not significantly different in the HW arm (OR = 1.20; 95% CI 0.76-1.88; P-0.442), or the HW + FM arm (OR = 1.16; 95% CI .0.74-1.82; P = 0.525). CONCLUSIONS: Influenza transmission was not reduced by interventions to promote hand washing and face mask use. This may be attributable to transmission that occurred before the intervention, poor facemask compliance, little difference in hand-washing frequency between study groups, and shared sleeping arrangements. A prospective study design and a careful analysis of sociocultural factors could improve future NPI studies.

BACKGROUND: The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004-2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases. METHODS AND FINDINGS: NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality. Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001). CONCLUSIONS: In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment.

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.

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.

Although pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34.6% in children aged <5 years); 66 patients (3.8%) died. A recognized pathogen was identified in 42.5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16.7% of all pneumonias, 41.2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417.1/100 000 per year) and in persons aged 50 years, influenza virus A (38.8/100 000 per year). These data can help guide health policy towards effective prevention strategies.

Background Prior to 2007, little information was available about the burden of influenza in Laos. We report data from the first laboratory-based influenza surveillance system established in the Lao People's Democratic Republic. Methods Three hospitals in the capital city of Vientiane began surveillance for influenza-like illness (ILI) in outpatients in 2007 and expanded to include hospitalized pneumonia patients in 2008. Nasal/throat swab specimens were collected and tested for influenza and other respiratory viruses by multiplex ID-TagTM respiratory viral panel (RVP) assay on a Luminex (R) 100x MAP IS instrument (Qiagen, Singapore). Results During January 2007 to December 2008, 287 of 526 (54 center dot 6%) outpatients with ILI were positive for at least one respiratory virus. Influenza was most commonly identified, with 63 (12 center dot 0%) influenza A and 92 (17 center dot 5%) influenza B positive patients identified. In 2008, six of 79 (7 center dot 6%) hospitalized pneumonia patients were positive for influenza A and four (5 center dot 1%) were positive for influenza B. Children < 5 years represented 19% of viral infections in outpatients and 38% of pneumonia inpatients. Conclusion Our results provide the first documentation of influenza burden among patients with febrile respiratory illness and pneumonia requiring hospitalization in Laos. Implementing laboratory-based influenza surveillance requires substantial investments in infrastructure and training. However, continuing outbreaks of avian influenza A/H5N1 in poultry and emergence of the 2009 influenza A(H1N1) pandemic strain further underscore the importance of establishing and maintaining influenza surveillance in developing countries.

We identified febrile pediatric outpatients seeking care for influenza like illness in Bangkok. Two nasal and 1 throat swab were tested using the QuickVue A+B rapid influenza kit and reverse transcription-polymerase chain reaction. Among 142 pandemic influenza A (H1N1)-positive patients, the QuickVue test identified 89 positive tests for a sensitivity of 62.7% (95% confidence interval [CI]: 54.7-70.6). Specificity was 99.2% (95% CI: 98-100). In the 0 to 2 years age group, sensitivity was 76.7% (95% CI: 61.5-91.8). Throat and nasal swabs are equally useful diagnostic specimens for reverse transcription-polymerase chain reaction diagnosis.

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.