Achuyt Bhattarai

Role of social networks in shaping disease transmission during a community outbreak of 2009 H1N1 pandemic influenza

Evaluating the impact of different social networks on the spread of respiratory diseases has been limited by a lack of detailed data on transmission outside the household setting as well as appropriate statistical methods. Here, from data collected during a H1N1 pandemic (pdm) influenza outbreak that started in an elementary school and spread in a semirural community in Pennsylvania, we quantify how transmission of influenza is affected by social networks. We set up a transmission model for which parameters are estimated from the data via Markov chain Monte Carlo sampling. Sitting next to a case or being the playmate of a case did not significantly increase the risk of infection; but the structuring of the school into classes and grades strongly affected spread. There was evidence that boys were more likely to transmit influenza to other boys than to girls (and vice versa), which mimicked the observed assortative mixing among playmates. We also investigated the presence of abnormally high transmission occurring on specific days of the outbreak. Late closure of the school (i.e., when 27% of students already had symptoms) had no significant impact on spread. School-aged individuals (6–18 y) facilitated the introduction and spread of influenza in households, but only about one in five cases aged >18 y was infected by a school-aged household member. This analysis shows the extent to which clearly defined social networks affect influenza transmission, revealing strong between-place interactions with back-and-forth waves of transmission between the school, the community, and the household.

Viral Shedding Duration of Pandemic Influenza A H1N1 Virus during an Elementary School Outbreak—Pennsylvania, May–June 2009

We report shedding duration of 2009 pandemic influenza A (pH1N1) virus from a school-associated outbreak in Pennsylvania during May through June 2009. Outbreak-associated students or household contacts with influenza-like illness (ILI) onset within 7 days of interview were recruited. Nasopharyngeal specimens, collected every 48 hours until 2 consecutive nonpositive tests, underwent real-time reverse transcriptase polymerase chain reaction (rRT-PCR) and culture for pH1N1 virus. Culture-positive specimens underwent virus titrations. Twenty-six (median age, 8 years) rRT-PCR-positive persons, for pH1N1 virus, were included in analysis. Median shedding duration from fever onset by rRT-PCR was 6 days (range, 1-13) and 5 days (range, 1-7) by culture. Following fever resolution virus was isolated for a median of 2 days (range, 0-5). Highest and lowest virus titers detected, 2 and 5 days following fever onset, were 3.2 and 1.2 log(10) TCID(50)/mL respectively. Overall, shedding duration in children and adults were similar to seasonal influenza viruses.

Household effects of school closure during pandemic (H1N1) 2009, Pennsylvania, USA.

To determine the effects of school closure, we surveyed 214 households after a 1-week elementary school closure because of pandemic (H1N1) 2009. Students spent 77% of the closure days at home, 69% of students visited at least 1 other location, and 79% of households reported that adults missed no days of work to watch children.

An Outbreak of 2009 Pandemic Influenza A (H1N1) Virus Infection in an Elementary School in Pennsylvania

In May 2009, one of the earliest outbreaks of 2009 pandemic influenza A virus (pH1N1) infection resulted in the closure of a semi-rural Pennsylvania elementary school. Two sequential telephone surveys were administered to 1345 students (85% of the students enrolled in the school) and household members in 313 households to collect data on influenza-like illness (ILI). A total of 167 persons (12.4%) among those in the surveyed households, including 93 (24.0%) of the School A students, reported ILI. Students were 3.1 times more likely than were other household members to develop ILI (95% confidence interval [CI], 2.3-4.1). Fourth-grade students were more likely to be affected than were students in other grades (relative risk, 2.2; 95% CI, 1.2-3.9). pH1N1 was confirmed in 26 (72.2%) of the individuals tested by real-time reverse-transcriptase polymerase chain reaction. The outbreak did not resume upon the reopening of the school after the 7-day closure. This investigation found that pH1N1 outbreaks at schools can have substantial attack rates; however, grades and classrooms are affected variably. Additional study is warranted to determine the effectiveness of school closure during outbreaks.

New global estimates of malaria deaths

www.thelancet.com Vol 380 August 11, 2012 559 Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/ 4 Kahama-Maro J, D’Acremont V, Mtasiwa D, Genton B, Lengeler C. Low quality of routine microscopy for malaria at diff erent levels of the health system in Dar es Salaam. Malaria J 2011; 10: 332. 5 Makani J, Matuja W, Liyombo E, Snow RW, Marsh K, Warrell DA. Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description. QJM 2003; 96: 355–62. New global estimates of malaria deaths

Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999–2010

Background Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period. Methods Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL) prevalence (SAP) among children 6–59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM. Results Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7–65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6–28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6–59 months declined 50% between 2005 (11.1%; 95% CI, 10.0–12.3%) and 2010 (5.5%; 95% CI, 4.7–6.4%) and U5CM declined by 45% between baseline (1995–9) and endpoint (2005–9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1–23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains. Conclusion Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1–24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival.

Investigating 2009 Pandemic Influenza A (H1N1) in US Schools: What Have We Learned?

US investigations of school-based outbreaks of 2009 pandemic influenza A (H1N1) virus infection characterized influenza-like illness (ILI) attack rates, transmission risk factors, and adherence to nonpharmaceutical interventions. We summarize seven school-based investigations conducted during April-June 2009 to determine what questions might be answered by future investigations. Surveys were administered 5-28 days after identification of the outbreaks, and participation rates varied among households (39-86%) and individuals (24-49%). Compared with adults (4%-10%) and children aged <4 years (2%-7%), elementary through university students had higher ILI attack rates (4%-32%). Large gatherings or close contact with sick persons were identified as transmission risk factors. More participants reported adherence to hygiene measures, but fewer reported adherence to isolation measures. Challenges included low participation and delays in survey initiation that potentially introduced bias. Although school-based investigations can increase our understanding of epidemiology and prevention strategy effectiveness, investigators should decide which objectives are most feasible, given timing and design constraints.

Framework for evaluating the health impact of the scale-up of malaria control interventions on all-cause child mortality in Sub-Saharan Africa

Abstract. Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malarias Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality.

Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005-2013.

BACKGROUND Improved understanding of the asymptomatic malaria parasite reservoir is a prerequisite to pursue malaria elimination efforts. We therefore characterised temporal trends and transporter polymorphisms in asymptomatic Plasmodium infections during the transition from high to low transmission in Zanzibar. METHODS Healthy individuals participating in cross-sectional surveys conducted 2005-2013 were screened for asymptomatic malaria by PCR. Complexity/diversity of infection and transporter polymorphisms were assessed in Plasmodium falciparum positive samples. Symptomatic samples were included for comparison of polymorphisms in 2013. RESULTS PCR-determined parasite prevalence declined from 21.1% (CI95% 17.4-24.9) to 2.3% (CI95% 1.7-2.9) from 2005 to 2013. P. falciparum remained the predominant species; prevalence was highest in children and young adults aged 5-25 years. Parasite densities and complexity of infection, but not population genetic diversity of P. falciparum, decreased from 2005-2009. pfcrt 76T (99.2-64.7%, p < 0.001) and pfmdr1 86Y frequencies (89.4-66.7%, p = 0.03) decreased over time. Pfmdr1 (a.a.86,184,1246) YYY and YYD haplotypes were more frequent in asymptomatic than symptomatic infections in 2013 (p < 0.001). CONCLUSIONS There is a declining, albeit persistent, reservoir of parasites present at low-densities in asymptomatic individuals in Zanzibar. This study revealed important characteristics of the remaining parasite population, including intriguing temporal trends in molecular markers associated with antimalarial resistance, which need to be further investigated.

Impact of Insecticide-Treated Net Ownership on All-Cause Child Mortality in Malawi, 2006-2010.

Abstract. Insecticide-treated nets (ITNs) have been shown to be highly effective at reducing malaria morbidity and mortality in children. However, there are limited studies that assess the association between increasing ITN coverage and child mortality over time, at the national level, and under programmatic conditions. Two analytic approaches were used to examine this association: a retrospective cohort analysis of individual children and a district-level ecologic analysis. To evaluate the association between household ITN ownership and all-cause child mortality (ACCM) at the individual level, data from the 2010 Demographic and Health Survey (DHS) were modeled in a Cox proportional hazards framework while controlling for numerous environmental, household, and individual confounders through the use of exact matching. To evaluate population-level association between ITN ownership and ACCM between 2006 and 2010, program ITN distribution data and mortality data from the 2006 Multiple Indicator Cluster Survey and the 2010 DHS were aggregated at the district level and modeled using negative binomial regression. In the Cox model controlling for household, child and maternal health factors, children between 1 and 59 months in households owning an ITN had significantly lower mortality compared with those without an ITN (hazard ratio = 0.75, 95% confidence interval [CI] = 0.62–90). In the district-level model, higher ITN ownership was significantly associated with lower ACCM (incidence rate ratio = 0.77; 95% CI = 0.60–0.98). These findings suggest that increasing ITN ownership may have contributed to the decline in ACCM during 2006–2010 in Malawi and represent a novel use of district-level data from nationally representative surveys.