BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.

Background: In 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults. Methods: We used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6 horizontal line 24months) and older adults (aged >/=60years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013-December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults. Results: We included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: -16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: -40%, 54%) against influenza B viruses. Conclusions: Our results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.

BACKGROUND: Despite having influenza vaccination policies and programs, countries in the Americas underutilize seasonal influenza vaccine, in part because of insufficient evidence about severe influenza burden. We aimed to estimate the annual burden of influenza-associated respiratory hospitalizations in the Americas. METHODS: Thirty-five countries in the Americas with national influenza surveillance were invited to provide monthly laboratory data and hospital discharges for respiratory illness (International Classification of Diseases 10th edition J codes 0-99) during 2010-2015. In three age-strata (<5, 5-64, and >/=65 years), we estimated the influenza-associated hospitalizations rate by multiplying the monthly number of respiratory hospitalizations by the monthly proportion of influenza-positive samples and dividing by the census population. We used random effects meta-analyses to pool age-group specific rates and extrapolated to countries that did not contribute data, using pooled rates stratified by age group and country characteristics found to be associated with rates. RESULTS: Sixteen of 35 countries (46%) contributed primary data to the analyses, representing 79% of the America's population. The average pooled rate of influenza-associated respiratory hospitalization was 90/100,000 population (95% confidence interval 61-132) among children aged <5 years, 21/100,000 population (13-32) among persons aged 5-64 years, and 141/100,000 population (95-211) among persons aged >/=65 years. We estimated the average annual number of influenza-associated respiratory hospitalizations in the Americas to be 772,000 (95% credible interval 716,000-829,000). CONCLUSIONS: Influenza-associated respiratory hospitalizations impose a heavy burden on health systems in the Americas. Countries in the Americas should use this information to justify investments in seasonal influenza vaccination-especially among young children and the elderly.

INTRODUCTION: Within-country differences in the timing of RSV and influenza epidemics have not been assessed in Argentina, the eighth largest country in the world by area. We compared seasonality for RSV and influenza both nationally and in each of the five regions to inform Argentina's prevention and treatment guidelines. METHOD: The Argentine National Laboratories and Health Institutes Administration collected respiratory specimens from clinical practices, outbreak investigations, and respiratory virus surveillance in 2007-2016; these were tested using immunofluorescence or RT-PCR techniques. We calculated weekly percent positive (PP) and defined season onset as >2 consecutive weeks when PP exceeded the annual mean for the respective year and region. Median season measures (onset, offset and peak) and the established mean method were calculated for each virus. RESULTS: An annual median 59,396 specimens were tested for RSV and 60,931 for influenza; 21-29% tested positive for RSV and 2-7% for influenza. National RSV activity began in April; region-specific start weeks varied by 7 weeks. Duration of RSV activity did not vary widely by region (16-18 weeks in duration). National influenza activity started in June; region-specific start weeks varied by 3 weeks. Duration of influenza epidemic activity varied more by region than that of RSV (7-13 weeks in duration). CONCLUSION: In Argentina, RSV and influenza activity overlapped during the winter months. RSV season tended to begin prior to the influenza season, and showed more variation in start week by region. Influenza seasons tended to vary more in duration than RSV seasons. This article is protected by copyright. All rights reserved.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and >/=75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0.1 to 6.4 per 100 000 individuals for people younger than 65 years, 2.9 to 44.0 per 100 000 individuals for people aged between 65 and 74 years, and 17.9 to 223.5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4.0-8.8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2.8-16.5 per 100 000 individuals), southeast Asia (3.5-9.2 per 100 000 individuals), and among people aged 75 years or older (51.3-99.4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING: None.

BACKGROUND: Despite widespread utilization of influenza vaccines, effectiveness (VE) has not been routinely measured in Latin America. METHODS: We used a case test-negative control design to estimate trivalent inactivated influenza VE against laboratory-confirmed influenza among hospitalized children aged 6months-5years and adults aged ≥60years which are age-groups targeted for vaccination. We sought persons with severe acute respiratory infections (SARI), hospitalized at 71 sentinel hospitals in Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Honduras, Panama, and Paraguay during January-December 2013. Cases had an influenza virus infection confirmed by real-time reverse transcription PCR (rRT-PCR); controls had a negative rRT-PCR result for influenza viruses. We used a two-stage random effects model to estimate pooled VE per target age-group, adjusting for the month of illness onset, age and preexisting medical conditions. RESULTS: We identified 2620 SARI patients across sites: 246 influenza cases and 720 influenza-negative controls aged ≤5years and 448 cases and 1206 controls aged ≥60years. The most commonly identified subtype among participants (48%) was the influenza A(H1N1)pdm09 virus followed by influenza A(H3N2) (34%) and influenza B (18%) viruses. Among children, the adjusted VE of full vaccination (one dose for previously vaccinated or two if vaccine naive) against any influenza virus SARI was 47% (95% confidence interval [CI]: 14-71%); VE was 58% (95% CI: 16-79%) against influenza A(H1N1)pdm09, and 65% (95% CI: -9; 89%) against influenza A(H3N2) viruses associated SARI. Crude VE of full vaccination against influenza B viruses associated SARI among children was 3% (95% CI: -150; 63). Among adults aged ≥60years, adjusted VE against any influenza SARI was 48% (95% CI: 34-60%); VE was 54% (95% CI: 37-69%) against influenza A(H1N1)pdm09, 43% (95% CI: 18-61%) against influenza A(H3N2) and 34% (95% CI: -4; 58%) against B viruses associated SARI. CONCLUSION: Influenza vaccine provided moderate protection against severe influenza illness among fully vaccinated young children and older adults, supporting current vaccination strategies.

Influenza is a preventable disease whose burden should be well documented, a necessary step in mobilizing vaccine program staff, providers and influenza vaccine target groups. We estimate the incidence of influenza hospitalizations from five Central America countries. We performed a meta-analysis of influenza-associated hospitalizations and in-hospital deaths. The highest annual incidence was observed among children aged <5 years (136 influenza-associated hospitalizations per 100,000 persons). Annually 7,625-11,289 influenza-associated hospitalizations and 352-594 deaths occurred in the sub-region. Our results suggest that a substantive number of persons are annually hospitalized because of influenza. Health officials should estimate how many illnesses could be averted through increased influenza vaccination.

BACKGROUND: Influenza-associated illness results in increased morbidity and mortality in the Americas. These effects can be mitigated with an appropriately chosen and timed influenza vaccination campaign. To provide guidance in choosing the most suitable vaccine formulation and timing of administration, it is necessary to understand the timing of influenza seasonal epidemics. OBJECTIVES: Our main objective was to determine if influenza occurs in seasonal patterns in the American tropics, and when these patterns occurred. METHODS: Publicly available, monthly seasonal influenza data from the Pan American Health Organization and WHO, from countries in the American tropics were obtained during 2002-2008 and 2011-2014 (excluding unseasonal pandemic activity during 2009-2010). For each country, we calculated the monthly proportion of samples that tested positive for influenza. We applied the monthly proportion data to a logistic regression model for each country. RESULTS: We analyzed 2002-2008 and 2011-2014 influenza surveillance data from the American tropics and identified 13 (81%) of 16 countries with influenza epidemics that, on average, started during May and lasted 4 months. CONCLUSIONS: The majority of countries in the American tropics have seasonal epidemics that start in May. Officials in these countries should consider the impact of vaccinating persons during April with the Southern Hemisphere formulation.

Seasonal influenza affects a considerable proportion of the global population each year. We assessed the association between subnational influenza activity and temperature, specific humidity and rainfall in three Central America countries, i.e. Costa Rica, Honduras and Nicaragua. Using virologic data from each country's national influenza centre, rainfall from the Tropical Rainfall Measuring Mission and air temperature and specific humidity data from the Global Land Data Assimilation System, we applied logistic regression methods for each of the five sub-national locations studied. Influenza activity was represented by the weekly proportion of respiratory specimens that tested positive for influenza. The models were adjusted for the potentially confounding co-circulating respiratory viruses, seasonality and previous weeks' influenza activity. We found that influenza activity was proportionally associated (P&lt;0.05) with specific humidity in all locations [odds ratio (OR) 1.21-1.56 per g/kg], while associations with temperature (OR 0.69-0.81 per degrees C) and rainfall (OR 1.01-1.06 per mm/day) were location-dependent. Among the meteorological parameters, specific humidity had the highest contribution (~3-15%) to the model in all but one location. As model validation, we estimated influenza activity for periods, in which the data was not used in training the models. The correlation coefficients between the estimates and the observed were ≤0.1 in 2 locations and between 0.6-0.86 in three others. In conclusion, our study revealed a proportional association between influenza activity and specific humidity in selected areas from the three Central America countries.

BACKGROUND: Influenza disease is a vaccine-preventable cause of morbidity and mortality. The Pan American Health Organization (PAHO) region has invested in influenza vaccines, but few estimates of influenza burden exist to justify these investments. We estimated influenza-associated deaths for 35 PAHO countries during 2002-2008. METHODS: Annually, PAHO countries report registered deaths. We used respiratory and circulatory (R&C) codes from seven countries with distinct influenza seasonality and high-quality mortality data to estimate influenza-associated mortality rates by age group (0-64, 65-74, and ≥75 years) with a Serfling regression model or a negative binomial model. We calculated the percent of all R&C deaths attributable to influenza by age group in these countries (etiologic fraction) and applied it to the age-specific mortality in 13 countries with good mortality data but poorly defined seasonality. Lastly, we grouped the remaining 15 countries into WHO mortality strata and applied the age and mortality stratum-specific rate of influenza mortality calculated from the 20 countries. We summed each country's estimate to arrive at an average total annual number and rate of influenza deaths in the Americas. RESULTS: For the 35 PAHO countries, we estimated an annual mean influenza-associated mortality rate of 2.1/100 000 among <65-year olds, 31.9/100 000 among those 65-74 years, and 161.8/100 000 among those ≥75 years. We estimated that annually between 40 880 and 160 270 persons (mean, 85 100) die of influenza illness in the PAHO region. CONCLUSION: Influenza remains an important cause of mortality in the Americas.

BACKGROUND: The demographic characteristics of pandemic influenza decedents among middle and low-income tropical countries are poorly understood. We explored the demographics of persons who died with influenza A (H1N1)pdm09 infection during 2009-2010, in seven countries in the American tropics. METHODS: We used hospital-based surveillance to identify laboratory-confirmed influenza deaths in Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, Panama and Dominican Republic. An influenza death was defined as a person who died within two weeks of a severe acute respiratory infection (SARI) defined as sudden onset of fever >38 degrees C, cough or sore-throat, and shortness of breath, or difficulty breathing requiring hospitalization, and who tested positive for influenza A (H1N1)pdm09 virus by real time polymerase chain reaction. We abstracted the demographic and clinical characteristics of the deceased from their medical records. RESULTS: During May 2009-June 2010, we identified 183 influenza deaths. Their median age was 32 years (IQR 18-46 years). One-hundred and one (55 %) were female of which 20 (20 %) were pregnant and 7 (7 %) were in postpartum. One-hundred and twelve decedents (61 %) had pre-existing medical conditions, (15 % had obesity, 13 % diabetes, 11 % asthma, 8 % metabolic disorders, 5 % chronic obstructive pulmonary disease, and 10 % neurological disorders). 65 % received oseltamivir but only 5 % received it within 48 h of symptoms onset. CONCLUSIONS: The pandemic killed young adults, pregnant women and those with pre-existing medical conditions. Most sought care too late to fully benefit from oseltamivir. We recommend countries review antiviral treatment policies for people at high risk of developing complications.

During 2001-2014, predominant influenza A(H1N1) and A(H3N2) strains in South America predominated in all or most subsequent influenza seasons in Central and North America. Predominant A(H1N1) and A(H3N2) strains in North America predominated in most subsequent seasons in Central and South America. Sharing data between these subregions may improve influenza season preparedness.

Data needed to guide influenza vaccine policies are lacking in tropical countries. We multiplied the number of severe acute respiratory infections by the proportion testing positive for influenza. There were approximately 6,699 influenza hospitalizations and 803 deaths in Costa Rica during 2009-2012, supporting continuation of a national influenza vaccine program.

OBJECTIVE: To determine trends in mortality from respiratory disease in several areas of Latin America between 1998 and 2009. METHODS: The numbers of deaths attributed to respiratory disease between 1998 and 2009 were extracted from mortality data from Argentina, southern Brazil, Chile, Costa Rica, Ecuador, Mexico and Paraguay. Robust linear models were then fitted to the rates of mortality from respiratory disease recorded between 2003 and 2009. FINDINGS: Between 1998 and 2008, rates of mortality from respiratory disease gradually decreased in all age groups in most of the study areas. Among children younger than 5 years, for example, the annual rates of such mortality - across all seven study areas - fell from 56.9 deaths per 100 000 in 1998 to 26.6 deaths per 100 000 in 2008. Over this period, rates of mortality from respiratory disease were generally highest among adults older than 65 years and lowest among individuals aged 5 to 49 years. In 2009, mortality from respiratory disease was either similar to that recorded in 2008 or showed an increase - significant increases were seen among children younger than 5 years in Paraguay, among those aged 5 to 49 years in southern Brazil, Mexico and Paraguay and among adults aged 50 to 64 years in Mexico and Paraguay. CONCLUSION: In much of Latin America, mortality from respiratory disease gradually fell between 1998 and 2008. However, this downward trend came to a halt in 2009, probably as a result of the (H1N1) 2009 pandemic.

BACKGROUND: In 2008, Rwanda established an influenza sentinel surveillance (ISS) system to describe the epidemiology of influenza and monitor for the emergence of novel influenza A viruses. We report surveillance results from August 2008 to July 2010. METHODS: We conducted ISS by monitoring patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) at 6 hospitals. For each case, demographic and clinical data, 1 nasopharyngeal specimen, and 1 oropharyngeal specimen were collected. Specimens were tested by real-time reverse-transcription polymerase chain reaction for influenza A and B viruses at the National Reference Laboratory in Rwanda. RESULTS: A total of 1916 cases (945 ILI and 971 SARI) were identified. Of these, 29.2% (n = 276) of ILI and 10.4% (n = 101) of SARI cases tested positive for influenza. Of the total influenza-positive cases (n = 377), 71.8% (n = 271) were A(H1N1) pdm09, 5.6% (n = 21) influenza A(H1), 7.7% (n = 29) influenza A(H3), 1.6% (n = 6) influenza A (unsubtyped), and 13.3% (n = 50) influenza B. The percentage of positivity for influenza viruses was highest in October-November and February-March, during peaks in rainfall. CONCLUSIONS: The implementation of ISS enabled characterization of the epidemiology and seasonality of influenza in Rwanda for the first time. Future efforts should determine the population-based influenza burden to inform interventions such as targeted vaccination.

BACKGROUND: We estimated rates of influenza-associated deaths and hospitalizations in Argentina, a country that recommends annual influenza vaccination for persons at high risk of complications from influenza illness. METHODS: We identified hospitalized persons and deaths in persons diagnosed with pneumonia and influenza (P&I, ICD-10 codes J10-J18) and respiratory and circulatory illness (R&C, codes I00-I99 and J00-J99). We defined the influenza season as the months when the proportion of samples that tested positive for influenza exceeded the annual median. We used hospitalizations and deaths during the influenza off-season to estimate, using linear regression, the number of excess deaths that occurred during the influenza season. To explore whether excess mortality varied by sex and whether people were age <65 or ≥65 years, we used Poisson regression of the influenza-associated rates. RESULTS: During 2002-2009, 2411 P&I and 8527 R&C mean excess deaths occurred annually from May to October. If all of these excess deaths were associated with influenza, the influenza-associated mortality rate was 6/100 000 person-years (95% CI 4-8/100,000 person-years for P&I and 21/100,000 person-years (95% CI 12-31/100,000 person-years) for R&C. During 2005-2008, we identified an average of 7868 P&I excess hospitalizations and 22,994 R&C hospitalizations per year, resulting in an influenza-associated hospitalization rate of 2/10,000 person-years (95% CI 1-3/10,000 person-years) for P&I and 6/10,000 person-years (95% CI 3-8/10 000 person-years) for R&C. CONCLUSION: Our findings suggest that annual rates of influenza-associated hospitalizations and death in Argentina were substantial and similar to neighboring Brazil.

In 2007 the Maryland Medical Examiner noted a potential cluster of fatal vascular access hemorrhages among hemodialysis patients, many of whom died outside of a health-care setting. To examine the epidemiology of fatal vascular access hemorrhages, we conducted a retrospective case review in District of Columbia, Maryland, and Virginia from January 2000 to July 2007 and a case-control study. Records from the Medical Examiner and Centers for Medicare and Medicaid Services were reviewed, from which 88 patients were identified as fatal vascular access hemorrhage cases. To assess risk factors, a subset of 20 cases from Maryland was compared to 38 controls randomly selected among hemodialysis patients who died from non-vascular access hemorrhage causes at the same Maryland facilities. Of the 88 confirmed cases, 55% hemorrhaged from arteriovenous grafts, 24% from arteriovenous fistulas, and 21% from central venous catheters. Of 82 case-patients with known location of hemorrhage, 78% occurred at home or in a nursing home. In the case-control analysis, statistically significant risk factors included the presence of an arteriovenous graft, access-related complications within 6 months of death, and hypertension; presence of a central venous catheter was significantly protective. Psychosocial factors and anticoagulant medications were not significant risk factors. Effective strategies to control vascular access hemorrhage in the home and further delineation of warning signs are needed. (Kidney International advance online publication, 13 June 2012; doi:10.1038/ki.2012.185.)

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 log10 TCID50/mL respectively. Overall, shedding duration in children and adults were similar to seasonal influenza viruses.

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. Additioanl study is warranted to determine the effectiveness of school closure during outbreaks.

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.

Hantaviruses are rodent-borne viruses capable of causing human disease. The Seoul virus is a hantavirus that causes hemorrhagic fever with renal syndrome in East Asia. To our knowledge, we report the first domestically acquired case of hemorrhagic fever with renal syndrome caused by the Seoul virus, confirmed by serology testing, reverse-transcriptase polymerase chain reaction, and nucleotide sequence analysis. The patient presented with myalgias and fever, and developed acute renal failure.