Influenza Surveillance Worldwide | CDC EID

Volume 15, Number 8–August 2009
Policy Review
Strategy to Enhance Influenza Surveillance Worldwide1
Justin R. Ortiz, Viviana Sotomayor, Osvaldo C. Uez, Otavio Oliva, Deborah Bettels, Margaret McCarron, Joseph S. Bresee, and Anthony W. Mounts
Author affiliations: University of Washington, Seattle, Washington, USA (J.R. Ortiz); Ministerio de Salud, Santiago, Chile (V. Sotomayor); Instituto Nacional de Epidemiología, Mar del Plata, Argentina (O.C. Uez); Pan American Health Organization, Washington, DC, USA (O. Oliva); and Centers for Disease Control and Prevention, Atlanta, Georgia, USA (D. Bettels, M. McCarron, J.S. Bresee, A.W. Mounts)

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Abstract
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.

The emergence of a novel strain of influenza virus A (H1N1) in April 2009 and its subsequent rapid global spread have focused attention on influenza surveillance capabilities worldwide (1). A consultation convened by the World Health Organization (WHO) in 2005 had previously concluded that the world was unprepared to respond to an influenza pandemic, due in part to inadequate global surveillance and response capacity (2). The International Health Regulations 2005 call for strengthened surveillance for all events that may constitute a "public health emergency of international concern"; such events include individual human cases of influenza caused by a new subtype of influenza virus A (3). As part of the International Health Regulations 2005 core surveillance and response capacity requirements, each Member State must develop and maintain capabilities to detect, assess, and report disease events nationally and internationally to WHO within 48 hours of confirmation. However, reviews of national pandemic planning indicate that surveillance systems are often inadequate to support current preparedness strategies (4–8). WHO has existing surveillance guidelines to help Member States implement universal surveillance for novel and pandemic influenza (9), but the guidelines lack the specificity that would enable many countries to establish operational surveillance plans.

Quality influenza surveillance systems are needed to enable countries to better understand influenza epidemiology, including disease incidence and severity, and help them implement appropriate prevention strategies. The challenges experienced by the United States and Mexico to rapidly determine the extent and severity of illness of the 2009 novel influenza A (H1N1) outbreak highlighted the need for systems that can reliably produce these estimates. Furthermore, global strategies to address other vaccine-preventable diseases have acknowledged the importance of establishing local disease burden (effects, severity, amount of illness, and costs) as a first step toward decisions about the introduction of vaccines into new countries. We describe a generic guideline for collecting data on severe acute respiratory infection (SARI), influenza-like illness (ILI), and laboratory-confirmed influenza that can be implemented in limited-resource settings.

Current Situation
Global Influenza Surveillance
For 60 years, the WHO Global Influenza Surveillance Network (GISN) has provided virologic information used in the biannual process of selecting strains for the Northern and Southern Hemisphere influenza vaccine formulations. However, its capacity to provide epidemiologic data or an alert of an emerging pandemic is limited. GISN currently comprises 122 National Influenza Centers in 87 countries and 4 WHO Collaborating Centers for Reference and Research on Influenza (10). Although this system has proven to be valuable, tropical and resource-limited countries (particularly in Africa) are underrepresented (11).

Influenza in Developing Countries
Virus transmission or clinical presentation may be altered by differences in cultural practices, the environment, geography, human genetics, and social structures. Enhanced influenza surveillance can permit assessment of a number of factors that may affect disease activity: population density, differences in prevalence and spectrum of chronic illness, proximity of the young and elderly, low proportion of elderly in the population, low school attendance, and school schedules that may not correspond with peak transmissibility season. The effectiveness of control measures such as social distancing and vaccination may differ between developed and developing settings because of these factors.

Available epidemiologic evidence suggests that influenza is common in tropical regions and contributes substantially to disability and use of healthcare resources (12–16). Data describing the seasonality and epidemiology of influenza in tropical areas are limited; however, some tropical countries report year-round human influenza activity (12), unlike in temperate regions where transmission occurs with marked seasonality. Because of these limited data, most of the understanding of seasonal influenza is derived from epidemiologic data collected in western Europe and North America. Nevertheless, estimates of a pandemic impact indicate that most deaths will be in developing countries and that more than half will occur in southern Asia and sub-Saharan Africa (17). A better understanding of the epidemiology of influenza in these areas would facilitate country-appropriate pandemic planning and vaccine policy development.

Objectives
The most efficient process for producing high-quality epidemiologic data for influenza-associated illness is sentinel surveillance. The primary limitation of most existing influenza sentinel-site networks that track ILIs has been that they often provide little epidemiologic data, do not produce data on disease incidence, and are focused on mild disease, which supports the notion that influenza is a benign disease. We propose that influenza surveillance should capture severe influenza outcomes as a primary measure. Hospital-based sentinel surveillance is the most efficient way to collect clinical data and laboratory specimens from persons with a prevalent and severe infectious disease.

Carefully placed sentinel sites can provide adequate information on the epidemiology of influenza without the need for comprehensive national case ascertainment or reporting. Placing surveillance sites where population data are known would permit calculation of population-based estimates of disease rates according to age and other demographic variables. In addition, collection of clinical specimens from persons from whom epidemiologic data are also collected would ensure virus strain surveillance and provide isolates that can be used for vaccine development.

A sentinel surveillance system can be used to monitor >1 disease, can be sustainable, and can integrate with and build upon existing systems. The system objectives are 1) describe the disease impact and epidemiology of severe, acute, febrile respiratory illness and define the proportion that is associated with influenza; 2) provide influenza virus isolates for monitoring changes in viral antigens and development of new vaccines; 3) contribute data for local pandemic planning and making decisions regarding vaccine policy; 4) provide infrastructure for an early warning system for outbreaks of new subtypes of influenza A viruses and new strains of existing subtypes; and 5) serve as a monitoring tool for pandemic influenza.

Components and Processes
Case Definitions
These surveillance guidelines use the existing WHO case definition for ILI and incorporate WHO guidance to define SARI in adults and children (Table 1). The case definitions fit within the existing framework for pandemic early warning, use existing definitions for ease of adoption, and rely on physical examination findings that do not require laboratory or radiographic criteria. In addition, SARI definitions may capture a broad spectrum of severe influenza-associated illness, including exacerbations of asthma, chronic obstructive pulmonary disease, and decompensated congestive heart failure, which may account for ≈75% of hospitalized influenza patients (16,20,21).

Sentinel Site Selection
Ideally, sites should represent a wide cross-section of ethnic and socioeconomic groups and should be in different climatic regions. Placement of sites in areas where the population denominator can be ascertained or estimated will facilitate incidence estimates. Ultimately, the choice of sentinel hospitals will often be based on practical issues such as human resources, communication infrastructure, and availability of specimen transport and testing. There is no ideal number of surveillance sites; the number chosen by a particular country will depend in part on sustainability and resources available.

Data Collection
Minimum data elements are outlined in Table 2. Data collected should be adequate for routine public health surveillance and description of key epidemiologic features of disease. Data can be broadened to include clinical signs and symptoms, potential exposures, laboratory data, and therapies.

Specimen Collection
Respiratory specimens should be collected early from all SARI patients, following established protocols (24). If resources do not allow collection from all patients, an unbiased systematic sampling scheme should be established. To develop quality estimates of incidence and severity, data and specimens from all or most SARI patients from a few facilities would be preferred over a small sample of SARI patients from multiple facilities.

Because seasonality, attack rates, and public health priorities differ from country to country, there is no generic number of specimens to be collected by each site. The number must be determined by the primary surveillance objective (e.g., understanding of seasonality, risk factor analysis, or determination of clinical outcomes) and must represent climatic and geographic regions. For example, a country with coastal, mountainous, and tropical regions may have different influenza activity in each region and may thus require more surveillance sites and increased specimen collection than neighbors or similarly sized countries. Therefore, the number of specimens collected must be approached on a case-by-case basis and depends on objectives of a country, country-specific geographic and climatic issues, and public health priorities.

Integration into National Reporting Systems
In countries with established national disease reporting systems, such as the Integrated Disease Surveillance Reporting system used in Africa (25), sentinel surveillance for SARI can be incorporated into the existing system. Because Integrated Disease Surveillance Reporting is generally a passive surveillance program, a few select sites should serve as embedded sentinel sites; intensive training and close follow-up should be conducted to ensure the quality of the reported data.

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