CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

Testing early warning and response systems through a full-scale exercise in Vietnam.

BACKGROUND: Simulation exercises can functionally validate World Health Organization (WHO) International Health Regulations (IHR 2005) core capacities. In 2018, the Vietnam Ministry of Health (MOH) conducted a full-scale exercise (FSX) in response to cases of severe viral pneumonia with subsequent laboratory confirmation for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) to evaluate the country's early warning and response capabilities for high-risk events. METHODS: An exercise planning team designed a complex fictitious scenario beginning with one case of severe viral pneumonia presenting at the hospital level and developed all the materials required for the exercise. Actors, controllers and evaluators were trained. In August 2018, a 3-day exercise was conducted in Quang Ninh province and Hanoi city, with participation of public health partners at the community, district, province, regional and national levels. Immediate debriefings and an after-action review were conducted after all exercise activities. Participants assessed overall exercise design, conduction and usefulness. RESULTS: FSX findings demonstrated that the event-based surveillance component of the MOH surveillance system worked optimally at different administrative levels. Detection and reporting of signals at the community and health facility levels were appropriate. Triage, verification and risk assessment were successfully implemented to identify a high-risk event and trigger timely response. The FSX identified infection control, coordination with internal and external response partners and process documentation as response challenges. Participants positively evaluated the exercise training and design. CONCLUSIONS: This exercise documents the value of exercising surveillance capabilities as part of a real-time operational scenario before facing a true emergency. The timing of this exercise and choice of disease scenario was particularly fortuitous given the subsequent appearance of COVID-19. As a result of this exercise and subsequent improvements made by the MOH, the country may have been better able to deal with the emergence of SARS-CoV-2 and contain it.

Developing monitoring and evaluation tools for event-based surveillance: experience from Vietnam.

BACKGROUND: In 2016-2017, Vietnam's Ministry of Health (MoH) implemented an event-based surveillance (EBS) pilot project in six provinces as part of Global Health Security Agenda (GHSA) efforts. This manuscript describes development and design of tools for monitoring and evaluation (M&E) of EBS in Vietnam. METHODS: A strategic EBS framework was developed based on the EBS implementation pilot project's goals and objectives. The main process and outcome components were identified and included input, activities, outputs, and outcome indicators. M&E tools were developed to collect quantitative and qualitative data. The tools included a supervisory checklist, a desk review tool, a key informant interview guide, a focus group discussion guide, a timeliness form, and an online acceptability survey. An evaluation team conducted field visits for assessment of EBS 5-9 months after implementation. RESULTS: The quantitative data collected provided evidence on the number and type of events that were being reported, the timeliness of the system, and the event-to-signal ratio. The qualitative and subjective data collected helped to increase understanding of the system's field utility and acceptance by field staff, reasons for non-compliance with established guidelines, and other factors influencing implementation. CONCLUSIONS: The use of M&E tools for the EBS pilot project in Vietnam provided data on signals and events reported, timeliness of reporting and response, perceptions and opinions of implementers, and fidelity of EBS implementation. These data were valuable for Vietnam's MoH to understand the function of the EBS program, and the success and challenges of implementing this project in Vietnam.

Event-Based Surveillance at Community and Healthcare Facilities, Vietnam, 2016-2017.

Surveillance and outbreak reporting systems in Vietnam required improvements to function effectively as early warning and response systems. Accordingly, the Ministry of Health of Vietnam, in collaboration with the US Centers for Disease Control and Prevention, launched a pilot project in 2016 focusing on community and hospital event-based surveillance. The pilot was implemented in 4 of Vietnam's 63 provinces. The pilot demonstrated that event-based surveillance resulted in early detection and reporting of outbreaks, improved collaboration between the healthcare facilities and preventive sectors of the ministry, and increased community participation in surveillance and reporting.

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection.

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.

La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe ­ c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.

La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.

Sustainable Model for Public Health Emergency Operations Centers for Global Settings.

Capacity to receive, verify, analyze, assess, and investigate public health events is essential for epidemic intelligence. Public health Emergency Operations Centers (PHEOCs) can be epidemic intelligence hubs by 1) having the capacity to receive, analyze, and visualize multiple data streams, including surveillance and 2) maintaining a trained workforce that can analyze and interpret data from real-time emerging events. Such PHEOCs could be physically located within a ministry of health epidemiology, surveillance, or equivalent department rather than exist as a stand-alone space and serve as operational hubs during nonoutbreak times but in emergencies can scale up according to the traditional Incident Command System structure.

Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014.

Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March-November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case-control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2-4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.

The challenges of global case reporting during pandemic A(H1N1) 2009.

During the 2009 A(H1N1) influenza pandemic, the World Health Organization (WHO) asked all Member States to provide case-based data on at least the first 100 laboratory-confirmed influenza cases to generate an early understanding of the pandemic and provide appropriate guidance to affected countries. In reviewing the pandemic surveillance strategy, we evaluated the utility of case-based data collection and the challenges in interpreting these data at the global level. To do this, we assessed compliance with the surveillance recommendation and data completeness of submitted case records and described the epidemiological characteristics of up to the first 110 reported cases from each country, aggregated into regions. From April 2009 to August 2011, WHO received over 18 000 case records from 84 countries. Data reached WHO at different time intervals, in different formats and without information on collection methods. Just over half of the 18 000 records gave the date of symptom onset, which made it difficult to assess whether the cases were among the earliest to be confirmed. Descriptive epidemiological analyses were limited to summarizing age, sex and hospitalization ratios. Centralized analysis of case-based data had little value in describing key features of the pandemic. Results were difficult to interpret and would have been misleading if viewed in isolation. A better approach would be to identify critical questions, standardize data elements and methods of investigation, and create efficient channels for communication between countries and the international public health community. Regular exchange of routine surveillance data will help to consolidate these essential channels of communication.

Pendant la pandémie de grippe à virus A(H1N1) de l'année 2009, l'Organisation mondiale de la Santé (OMS) a demandé à tous les États membres de fournir les données par cas sur au moins les 100 premiers cas de grippe confirmés en laboratoire afin d'obtenir une compréhension précoce de la pandémie et de fournir les directives appropriées aux pays touchés. En examinant la stratégie de surveillance de la pandémie, nous avons évalué l'utilité de la collecte des données par cas et les défis à relever dans l'interprétation de ces données au niveau mondial. Pour ce faire, nous avons évalué le respect des recommandations en matière de surveillance et l'exhaustivité des données des dossiers des cas soumis, et nous avons décrit les caractéristiques épidémiologiques des 110 premiers cas signalés de chaque pays, regroupés en régions. Sur la période allant d'avril 2009 à août 2011, l'OMS a reçu plus de 18 000 dossiers de cas fournis par 84 pays. Les données sont parvenues à l'OMS à différents intervalles de temps, sous différents formats et sans informations sur les méthodes de collecte. À peine plus de la moitié des 18 000 dossiers a donné la date d'apparition des symptômes, ce qui ne permet pas d'évaluer si les cas reçus faisaient partie des premiers cas à être confirmés. Les analyses épidémiologiques descriptives se sont limitées à synthétiser les rapports d'âge, de masculinité et d'hospitalisation. L'analyse centralisée des données par cas n'a que très peu de valeur dans la description des principales caractéristiques de la pandémie. Les résultats sont difficiles à interpréter et pourraient induire en erreur s'ils sont pris isolément. Une meilleure approche consisterait à identifier les questions essentielles, à normaliser les éléments des données et les méthodes d'investigation, et à créer des canaux efficaces de communication entre les pays et la communauté de la santé publique internationale. Les échanges réguliers de données de surveillance de routine aideront à consolider ces canaux de communication essentiels.

Durante la pandemia de gripe A (H1N1) del año 2009, la Organización Mundial de la salud (OMS) pidió a todos los Estados miembros que proporcionaran datos de hasta los primeros 100 casos de gripe confirmados en laboratorios con objeto de comprender con rapidez la pandemia y proporcionar orientación adecuada a los países afectados. Con objeto de examinar la estrategia de vigilancia de la pandemia, hemos evaluado la utilidad de la recogida de datos sobre casos y los desafíos que supuso la interpretación de esos datos a nivel internacional. Para ello, evaluamos el cumplimiento con las recomendaciones de vigilancia y la integridad de los datos de los registros enviados y describimos las características epidemiológicas de, como mucho, los 110 primeros casos de cada país, agrupados por regiones. Entre abril de 2009 y agosto de 2011, la OMS recibió más de 18 000 registros de casos de 84 países en intervalos de tiempo y formatos distintos, y sin información alguna sobre los métodos de recogida. Solo algo más de la mitad de los 18 000 registros indicaba la fecha de aparición de los síntomas, lo que dificultó evaluar si los casos se encontraban entre los primeros que se confirmaron. Los análisis epidemiológicos descriptivos se limitaron a resumir las proporciones por edad, sexo y hospitalización. Los análisis centralizados de datos sobre casos tuvieron poco valor en la descripción de las características fundamentales de la epidemia. Fue difícil interpretar los resultados, que habrían resultado engañosos si se hubieran observado de forma aislada. Un enfoque más apropiado permitiría identificar las cuestiones críticas, estandarizar los datos y los métodos de investigación, y crear canales de comunicación entre los países y la comunidad sanitaria internacional. El intercambio regular de datos de vigilancia rutinarios ayudará a consolidar dichos canales de comunicación fundamentales.

Notifiable disease reporting among public sector physicians in Nigeria: a cross-sectional survey to evaluate possible barriers and identify best sources of information.

BACKGROUND: Since 2001, Nigeria has collected information on epidemic-prone and other diseases of public health importance through the Integrated Disease Surveillance and Response system (IDSR). Currently 23 diseases are designated as "notifiable" through IDSR, including human infection with avian influenza (AI). Following an outbreak of highly pathogenic avian influenza A(H5N1) in Nigerian poultry populations in 2006 and one laboratory confirmed human infection in 2007, a study was carried out to describe knowledge, perceptions, and practices related to infectious disease reporting through the IDSR system, physicians' preferred sources of heath information, and knowledge of AI infection in humans among public sector physicians in Nigeria. METHODS: During November to December 2008, 245 physicians in six Nigerian cities were surveyed through in-person interviews. Survey components included reporting practices for avian influenza and other notifiable diseases, perceived obstacles to disease reporting, methods for obtaining health-related information, and knowledge of avian influenza among participating physicians. RESULTS: All 245 respondents reported that they had heard of AI and that humans could become infected with AI. Two-thirds (163/245) had reported a notifiable disease. The most common perceived obstacles to reporting were lack of infrastructure/logistics or reporting system (76/245, 31%), lack of knowledge among doctors about how to report or to whom to report (64/245, 26%), and that doctors should report certain infectious diseases (60/245, 24%). Almost all participating physicians (>99%) reported having a cell phone that they currently use, and 86% reported using the internet at least weekly. CONCLUSIONS: Although the majority of physicians surveyed were knowledgeable of and had reported notifiable diseases, they identified many perceived obstacles to reporting. In order to effectively identify human AI cases and other infectious diseases through IDSR, reporting system requirements need to be clearly communicated to participating physicians, and perceived obstacles, such as lack of infrastructure, need to be addressed. Future improvements to the reporting system should account for increased utilization of the internet, as well as cell phone and email-based communication.

Global VAX: A U.S. contribution to global COVID-19 vaccination efforts, 2021-2023.

In December 2021 the U.S. Government announced a new, whole-of-government $1.8 billion effort, the Initiative for Global Vaccine Access (Global VAX) in response to the global COVID-19 pandemic. Using the foundation of decades of U.S. government investments in global health and working in close partnership with local governments and key global and multilateral organizations, Global VAX enabled the rapid acceleration of the global COVID-19 vaccine rollout in selected countries, contributing to increased COVID-19 vaccine coverage in some of the world's most vulnerable communities. Through Global VAX, the U.S. Government has supported 125 countries to scale up COVID-19 vaccine delivery and administration while strengthening primary health care systems to respond to future health crises. The progress made by Global VAX has paved the way for a stronger global recovery and improved global health security.

Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study.

BACKGROUND: Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries. METHODS AND FINDINGS: We obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012). CONCLUSIONS: We estimate that 2009 global pandemic respiratory mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons <65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary.

Trends in mortality from respiratory disease in Latin America since 1998 and the impact of the 2009 influenza pandemic.

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.

Seasonality, timing, and climate drivers of influenza activity worldwide.

BACKGROUND: Although influenza is a vaccine-preventable disease that annually causes substantial disease burden, data on virus activity in tropical countries are limited. We analyzed publicly available influenza data to better understand the global circulation of influenza viruses. METHOD: We reviewed open-source, laboratory-confirmed influenza surveillance data. For each country, we abstracted data on the percentage of samples testing positive for influenza each epidemiologic week from the annual number of samples testing positive for influenza. The start of influenza season was defined as the first week when the proportion of samples that tested positive remained above the annual mean. We assessed the relationship between percentage of samples testing positive and mean monthly temperature with use of regression models. FINDINGS: We identified data on laboratory-confirmed influenza virus infection from 85 countries. More than one influenza epidemic period per year was more common in tropical countries (41%) than in temperate countries (15%). Year-round activity (ie, influenza virus identified each week having ≥ 10 specimens submitted) occurred in 3 (7%) of 43 temperate, 1 (17%) of 6 subtropical, and 11 (37%) of 30 tropical countries with available data (P = .006). Percentage positivity was associated with low temperature (P = .001). INTERPRETATION: Annual influenza epidemics occur in consistent temporal patterns depending on climate.

Facing the future of respiratory virus surveillance: "The mosaic surveillance framework".

It is impossible to address the many complex needs of respiratory virus surveillance with a single system. Therefore, multiple surveillance systems and complementary studies must fit together as tiles in a "mosaic" to provide a complete picture of the risk, transmission, severity, and impact of respiratory viruses of epidemic and pandemic potential. Below we present a framework (WHO Mosaic Respiratory Surveillance Framework) to assist national authorities to identify priority respiratory virus surveillance objectives and the best approaches to meet them; to develop implementation plans according to national context and resources; and to prioritize and target technical assistance and financial investments to meet most pressing needs.

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.

Performance of case definitions used for influenza surveillance among hospitalized patients in a rural area of India.

OBJECTIVE: To assess case definitions for influenza in a rural community in India. METHODS: Residents of the study area who were hospitalized for any acute medical condition for at least one night between May 2009 and April 2011 were enrolled. Respiratory specimens were collected and tested for influenza viruses in a reverse-transcription polymerase chain reaction (PCR). The PCR results were taken as the "gold standard" in evaluating the performance of several case definitions. FINDINGS: Of the 3179 patients included in the final analysis, 21% (665) were PCR-positive for influenza virus, 96% reported fever and 4% reported shortness of breath. The World Health Organization (WHO) case definition for severe acute respiratory illness had a sensitivity of 11% among patients aged < 5 years and of 3% among older patients. When shortness of breath was excluded from the definition, sensitivities increased (to 69% and 70%, respectively) and corresponding specificities of 43% and 53% were recorded. Among patients aged ≥ 5 years, WHO's definition of a case of influenza-like illness had a sensitivity of 70% and a specificity of 53%. The addition of "cough and reported or measured fever" increased sensitivity to 80% but decreased specificity to 42%. CONCLUSION: The inclusion of shortness of breath in WHO's case definition for severe acute respiratory illness may grossly underestimate the burden posed by influenza in hospitals. The exclusion of shortness of breath from this definition or, alternatively, the inclusion of "cough and measured or reported fever" may improve estimates of the burden.

Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis.

BACKGROUND: Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. METHODS AND FINDINGS: Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions--Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, The Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom--to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5-14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50-64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). CONCLUSIONS: Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes. Please see later in the article for the Editors' Summary.

SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey.

INTRODUCTION: As of 26 March 2021, the Africa Centres for Disease Control and Prevention had reported 4 159 055 cases of COVID-19 and 111 357 deaths among the 55 African Union member states; however, no country has published a nationally representative serosurvey as of October 2021. Such data are vital for understanding the pandemic's progression on the continent, evaluating containment measures, and policy planning. METHODS: We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was estimated after applying sampling weights. RESULTS: The overall weighted seroprevalence was 2.6% (95% CI 1.9% to 3.4%). This was 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0% to 2.5%), and urban seropositivity was 4.2% (95% CI 2.6% to 5.7%). DISCUSSION: Overall seroprevalence was low compared with countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone). This has ramifications for the country's third wave (which started in June 2021), during which the average number of daily reported cases was 87 by the end of the month:this could potentially be on the order of 3700 actual infections per day, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant under-reporting of incidence and mortality across the continent.

SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey.

Background As of 26 March 2021, the Africa CDC had reported 4,159,055 cases of COVID-19 and 111,357 deaths among the 55 African Union Member States; however, no country has published a nationally representative serosurvey as of May 2021. Such data are vital for understanding the pandemic's progression on the continent, evaluating containment measures, and policy planning. Methods We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on socio-demographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was was estimated after applying sampling weights. Findings The overall weighted seroprevalence was 2.6% (95% CI 1.9-3.4). This is 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0-2.5), and urban seropositivity was 4.2% (95% CI 2.6-5.7). Interpretation Although overall seroprevalence was low compared to countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone), our findings indicate enormous underreporting of active cases. This has ramifications for the country's third wave (which started in June 2021), where the average number of daily reported cases was 87 by the end of the month: this could potentially be on the order of 3,700 actual infections, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant underreporting of incidence and mortality across the continent.

Strategy to enhance influenza surveillance worldwide.

The emergence of a novel strain of influenza virus A (H1N1) in April 2009 focused attention on influenza surveillance capabilities worldwide. In consultations before the 2009 outbreak of influenza subtype H1N1, the World Health Organization had concluded that the world was unprepared to respond to an influenza pandemic, due in part to inadequate global surveillance and response capacity. We describe a sentinel surveillance system that could enhance the quality of influenza epidemiologic and laboratory data and strengthen a country's capacity for seasonal, novel, and pandemic influenza detection and prevention. Such a system would 1) provide data for a better understanding of the epidemiology and extent of seasonal influenza, 2) provide a platform for the study of other acute febrile respiratory illnesses, 3) provide virus isolates for the development of vaccines, 4) inform local pandemic planning and vaccine policy, 5) monitor influenza epidemics and pandemics, and 6) provide infrastructure for an early warning system for outbreaks of new virus subtypes.