Modes of Transmission of Influenza B Virus in Households

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.published_or_final_versio

Reconstructing unseen transmission events to infer dengue dynamics from viral sequences.

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens

Standardized Interpretation of Chest Radiographs in Cases of Pediatric Pneumonia From the PERCH Study.

BACKGROUND.: Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials. METHODS.: The Pneumonia Etiology Research for Child Health (PERCH) study enrolled children aged 1-59 months hospitalized with WHO-defined severe and very severe pneumonia from 7 low- and middle-income countries. An interpretation process categorized each CXR into 1 of 5 conclusions: consolidation, other infiltrate, both consolidation and other infiltrate, normal, or uninterpretable. Two members of a 14-person reading panel, who had undertaken training and standardization in CXR interpretation, interpreted each CXR. Two members of an arbitration panel provided additional independent reviews of CXRs with discordant interpretations at the primary reading, blinded to previous reports. Further discordance was resolved with consensus discussion. RESULTS.: A total of 4172 CXRs were obtained from 4232 cases. Observed agreement for detecting consolidation (with or without other infiltrate) between primary readers was 78% (κ = 0.50) and between arbitrators was 84% (κ = 0.61); agreement for primary readers and arbitrators across 5 conclusion categories was 43.5% (κ = 0.25) and 48.5% (κ = 0.32), respectively. Disagreement was most frequent between conclusions of other infiltrate and normal for both the reading panel and the arbitration panel (32% and 30% of discordant CXRs, respectively). CONCLUSIONS.: Agreement was similar to that of previous evaluations using the WHO methodology for detecting consolidation, but poor for other infiltrates despite attempts at a rigorous standardization process

Optimal Design of Intervention Studies to Prevent Influenza in Healthy Cohorts

Background: Influenza cohort studies, in which participants are monitored for infection over an epidemic period, are invaluable in assessing the effectiveness of control measures such as vaccination, antiviral prophylaxis and nonpharmaceutical interventions (NPIs). Influenza infections and illnesses can be identified through a number of approaches with different costs and logistical requirements. Methodology and Principal Findings: In the context of a randomized controlled trial of an NPI with a constrained budget, we used a simulation approach to examine which approaches to measuring outcomes could provide greater statistical power to identify an effective intervention against confirmed influenza. We found that for a short epidemic season, the optimal design was to collect respiratory specimens at biweekly intervals, as well as following report of acute respiratory illness (ARI), for virologic testing by reverse transcription polymerase chain reaction (RT-PCR). Collection of respiratory specimens only from individuals reporting ARI was also an efficient design particularly for studies in settings with longer periods of influenza activity. Collection of specimens only from individuals reporting a febrile ARI was less efficient. Collection and testing of sera before and after influenza activity appeared to be inferior to collection of respiratory specimens for RT-PCR confirmation of acute infections. The performance of RT-PCR was robust to uncertainty in the costs and diagnostic performance of RT-PCR and serological tests

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines