Paho-Cdc Generic Protocol Influenza Surveillance
Paho-Cdc Generic Protocol Influenza Surveillance
Paho-Cdc Generic Protocol Influenza Surveillance
Influenza Surveillance
PAHO Health Surveillance and Disease Management Area
Communicable Disease Unit Viral Disease Team
15 December 2006
Table of Contents
1. Preface............................................................................................................................. 1 2. Background ..................................................................................................................... 2 2.1. General..................................................................................................................... 2 2.2. Pandemic Influenza.................................................................................................. 3 2.3. Influenza Surveillance ............................................................................................. 3 3. Justification for a Surveillance System........................................................................... 4 4. Objectives of an Influenza Surveillance System ............................................................ 5 4.1. Sentinel Surveillance System................................................................................... 6 4.2. Enhanced Nationwide Notifiable Disease Surveillance System.............................. 7 5. Sentinel Surveillance ...................................................................................................... 8 5. 1. Introduction............................................................................................................. 8 5.2. Case Definitions....................................................................................................... 8 5.3. Surveillance of Influenza-Like Illness (ILI) in Ambulatory Patients ...................... 9 5.4. Surveillance of Severe Acute Respiratory Infection (SARI) in Hospitalized Patients.......................................................................................................................... 10 5.5. Specific Objectives ................................................................................................ 11 5.6. Selection of Sentinel Sites ..................................................................................... 11 5.7. Organization of Surveillance Facilities.................................................................. 12 5. 8. Implementation ..................................................................................................... 14 5.9. Surveillance Data Collection and Flow ................................................................. 14 5.10. Processing Respiratory Samples .......................................................................... 15 5.11. Data Analysis ....................................................................................................... 17 5.12. Sentinel Surveillance Performance Indicators ..................................................... 18 6. Enhanced Nationwide Notifiable Disease Surveillance ............................................... 20 6.1. Introduction............................................................................................................ 20 6.2. Objectives .............................................................................................................. 21 6.3. Triggers for Outbreak Investigations ..................................................................... 21 6.4. Nationwide Surveillance System Organization ..................................................... 23 6.5. Nationwide Surveillance System Education and Awareness................................. 23 6.6. Nationwide Surveillance System Reporting .......................................................... 24 6.7. Rapid Response to Investigation Triggers ............................................................. 24 6.8. Nationwide Surveillance Responsibilities ............................................................. 26 6.9. Nationwide Surveillance System Performance Indicators..................................... 28 8. References..................................................................................................................... 28 9. Annexes......................................................................................................................... 32 Annex 1: Surveillance Data Collection and Flow, Registry Instruments ..................... 32 Annex 2: Techniques for Respiratory Sampling........................................................... 41 Annex 2: Techniques for Respiratory Sampling........................................................... 42 Annex 3: IMCI case definitions:................................................................................... 43
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1. Preface
Despite the substantial contribution of human influenza to morbidity and mortality, surveillance for the disease has not been standardized worldwide, and the epidemiology of the illness in tropical, subtropical, and developing regions is not as well understood as it is in other parts of the world. In addition, the current epizootic of avian influenza A (H5N1) among poultry and wild birds, and the concomitant risk to human health highlight the necessity for surveillance systems capable of detecting influenza viruses with pandemic potential. In 2005, at the 58th World Health Assembly, the World Health Organization (WHO) formally adopted the revised International Health Regulations (IHR 2005) as a key global instrument against the international spread of disease (1). The Assembly also adopted a resolution entitled Strengthening Pandemic Influenza Preparedness and Response (2), which calls for WHO and its Member States to fortify and coordinate national strategies to prepare for an influenza pandemic. The following year, WHO adopted a resolution, Application of the International Health Regulations (2005), to address the pandemic threat from human cases of avian influenza (3). The resolution urges Member States to immediately comply on a voluntary basis with the revised IHR 2005 and to follow all mechanisms and procedures set out therein for any disease that might constitute a public health emergency of international concern. The document also urges the application of Part II of the IHR 2005 pertaining to surveillance, information-sharing, consultation, verification, and public health response with regard to any new influenza subtype with pandemic potential. Surveillance is the foundation of all efforts to understand and control influenza. The monitoring of epidemic influenza disease patterns is essential for yearly planning of prevention and response activities, for the identification of groups at high risk for complications, and for estimating the burden of influenza in terms of both health and economic impact (4). Influenza surveillance is essential for early detection and for the antigenic and genetic evaluation of new variants or subtypes of the influenza virus, including any strains with pandemic potential. The purpose of this generic protocol is to provide support for Pan American Health Organization (PAHO) Member States to improve influenza surveillance by integrating epidemiologic and laboratory components into a single system. To that end, the protocol proposes strengthening the national capacity of PAHO Member States by developing a sentinel surveillance system and an influenza notifiable disease surveillance system, both of which will complement existing structures whenever present. An expected result of this activity is that the new surveillance system, which will be implemented with standardized methodologies and procedures, will allow for the assessment of influenza activity throughout the Region of the Americas and will enable the comparison of circulating influenza strains -- and the number of patients meeting case definitions for infectious respiratory disease -- with other WHO Regions with other sub-regions of the Americas, and between PAHO Member States.
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The development of this generic protocol constitutes a collaborative effort by the PAHO, WHO Regional Office for the Americas, the Centers for Disease Control and Prevention of the United States (CDC), and representatives of PAHO Member States.
2. Background
2.1. General
Influenza is an acute contagious viral respiratory disease characterized by fever, headache, myalgia, prostration, coryza, sore throat, and cough (5, 6). Symptoms and signs differ according to the age of those infected (5). Hospitalization and deaths occur mainly in high-risk groups: children in their first two years of life, the elderly, and the chronically ill (7, 8). The influenza virus spreads rapidly around the world in seasonal epidemics (9). In temperate regions, seasonal influenza typically occurs every year in the late fall or winter (9). In tropical and subtropical regions, the seasonality of influenza is less clearly defined, with background activity occurring year-round (10). The disease causes a considerable economic burden in relation to health care costs and lost productivity in temperate regions (8). Moreover, there is increasing evidence that the burden of influenza disease in tropical and subtropical countries may be substantial (10). Influenza infection is caused by RNA viruses belonging to the Orthomyxoviridae family. There are three types of influenza viruses, A, B, and C, and humans can be infected with all three types (9). Influenza A and B viruses cause epidemic disease in humans and type C viruses usually cause a mild, cold-like illness. Influenza A viruses are further designated by subtype according to their surface proteins: hemagglutinin and neuraminidase (9). To date, 16 hemagglutinin and 9 neuraminidase subtypes have been identified (11). Influenza A infects multiple species, including humans, other mammals, and wild and domestic birds (9).The current human influenza A subtypes in circulation are H1N1 and H3N2 (12). Frequent changes occur in the genetic makeup of influenza A viruses, and these changes constitute the basis for epidemics and pandemics (9). Minor genetic changes are called antigenic drift and result in immunologically significant alterations to virus surface antigens. Drift is an ongoing process that results in the appearance of new antigenic variants requiring yearly updates to the strain composition of the influenza vaccine (6). Major genetic changes are called antigenic shift and represent a more radical change that refers to the appearance of an influenza virus bearing either a novel hemagglutinin or a novel combination of hemagglutinin and neuraminidase. Antigenic shift may occur as a result of mutation or genetic reassortment of human and animal influenza A viruses (9). Antigenic shifts can lead to pandemics, but only if the new virus is sufficiently transmissible among humans to maintain epidemic activity and is capable of causing disease (9). Yearly vaccination is recommended for those at highest risk of morbidity and mortality (7). Influenza antiviral therapy is an important adjunct to the annual influenza vaccination for the treatment and prevention of influenza. Influenza antiviral drugs are effective in preventing infection, and they reduce the symptoms of infection when started during the early stages of the
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disease and can decrease influenza-associated complications (7). There are two classes of antiviral medications with activity against influenza viruses: the adamantanes, including amantadine and rimantadine; and the neuraminidase inhibitors, including oseltamivir and zanamivir. The adamantane class, which only has activity against influenza A viruses, has been in use for decades; however, high rates of adamantane resistance have been reported recently in the United States, Canada, and Asia (13, 14). Given the resistance of human influenza to the adamantane class of antiviral drugs, the neuraminidase inhibitors oseltamivir and zanamivir are recommended by WHO for the treatment and prophylaxis of human influenza virus infection (15).
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In the Region of the Americas, there are 25 National Influenza Centers connected to the WHO Collaborating Center for Reference and Research of Influenza at CDC in Atlanta, Georgia, USA (20). Increased participation by each PAHO Member State in the surveillance for influenza viruses will enhance each country's ability to monitor the following: viral respiratory diseases including influenza, influenza-like illness (ILI), and severe acute respiratory infection (SARI); develop vaccine policy; and help build global and regional strategies for the prevention and control of influenza.
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In the current context of avian influenza outbreaks in humans and the consequent risk of pandemic influenza, PAHO is carrying out different activities to strengthen influenza surveillance. Epidemiologic surveillance is a fundamental tool for evaluating disease burden, and with it, countries can evaluate the impact of preparedness and control measures should a new virus subtype with pandemic potential be detected.
Current epidemiologic data are limited in some countries, such as those in tropical regions where influenza seasonality is not fully characterized, making it difficult to select vaccine strains and to determine the appropriate timing for vaccination. In addition, the existing surveillance systems have low sensitivity for detecting new influenza strains, and they are not integrated with animalhealth surveillance. Moreover, there is a need to develop practical support for local, intermediate, and national health teams to enable them to organize and implement an influenza surveillance system representative of the geographic and demographic makeup of a country. Such a system would need to integrate surveillance of circulating influenza strains and influenza-associated morbidity and mortality to meet surveillance objectives.
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verification, and investigation of influenza-related events in a timely manner and for the adoption of the necessary control measures. The Sentinel Surveillance and Enhanced National Notifiable Disease Surveillance systems are further described below, and implementation protocols for influenza surveillance and reporting follow in Sections 5 and 6, respectively.
ILI Surveillance: Ambulatory clinic-based sentinel surveillance for illnesses that meet the case definition of ILI. SARI Surveillance: Hospital-based sentinel surveillance for illnesses and deaths that meet the case definition for SARI.
Ideally, both of these components will be implemented within a country, and the resulting information will be used to meet the established surveillance objectives. However, if a countrys resources and technical capacity cannot support both components, SARI surveillance in sentinel hospitals is recommended as a minimum standard.
The Sentinel Surveillance System components
Surveillance System This includes all surveillance activities including Enhanced Nationwide Notifiable Disease Surveillance, Sentinel Surveillance, and other surveillance enhancements.
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Sentinel Surveillance Respiratory infection surveillance based in select surveillance hospitals and clinics that uses a clinical case definition and systematic sampling of a subset of cases for laboratory confirmation. Sentinel Unit This is the most basic level of the Surveillance System. The Sentinel Unit is comprised of a Local Epidemiology Office, Sentinel Hospital(s), Sentinel Clinic(s), and a Local Sentinel Laboratory. Local Epidemiology Office This is the office that oversees the most basic level of the Surveillance System and integrates surveillance data in the area under its responsibility. Sentinel Hospital This is a component of the Sentinel Unit. Cases meeting the definition of Severe Acute Respiratory Infection are recorded in Sentinel Hospitals. Sentinel Clinic This is a component of the Sentinel Unit. Cases meeting the definition of Influenza-like Illness are recorded in Sentinel Clinics. Sentinel Laboratory This is the laboratory component of most Sentinel Units. National Reference Laboratory This is the reference laboratory for the entire Surveillance System. Often, it will be a National Influenza Center. It receives clinical specimens from Local Sentinel Laboratories for confirmation and other tests. Intermediate Level Epidemiology Office This office within the Surveillance System is one level above the Sentinel Unit. In many countries, this will be a Provincial Health Department. The role of the Intermediate Epidemiology Office will be to collect, aggregate, analyze, and disseminate Sentinel Unit surveillance data from the area under its responsibility. Small countries and countries with few Sentinel Units may choose not to have this level of organization. National Level Epidemiology Office This is the highest level of the Surveillance System above the Intermediate Level Epidemiology Offices. In many countries, this will be the National Ministry of Health. The role of the National Level Epidemiology Office will be to collect, aggregate, analyze, and disseminate all surveillance data from within the country.
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about unusual or unexpected respiratory diseases will initiate public health inquiries and, if necessary, outbreak investigations. Respiratory infections associated with epidemiologic triggers (e.g., clusters of unusual severity, related to travel, or exposure to sick animals) should initiate outbreak investigations.
5. Sentinel Surveillance
5. 1. Introduction
A Sentinel Unit comprises a network of health care facilities and a local laboratory. These establishments integrate morbidity, mortality, and laboratory data, and they generate highquality, timely information. A Sentinel Unit would comprise a Sentinel Hospital or a Sentinel Clinic, or both. Ideally, the patient populations served by the Sentinel Unit would be well characterized, and therefore allow for the calculation of attack rates (cases per service population over time). In most cases, however, the size of the population served by sentinel sites may be difficult to determine, and surveillance data will be presented as a proportion of cases per total clinic consultations or total hospitalizations. Surveillance for ILI among ambulatory patients is conducted in sentinel clinics, and surveillance for SARI-associated morbidity and mortality is conducted in sentinel hospitals. In both cases, laboratory confirmation of a subset is obtained by testing a determined number of systematically chosen cases. Local Sentinel Laboratories test the samples for influenza and other respiratory viruses, and those with results positive for influenza are then characterized at the National Reference Laboratory or at a WHO-affiliated National Influenza Center. Epidemiologic, clinical, and laboratory data are analyzed in Local Epidemiology Offices and then sent to epidemiology offices at the national level for consolidation and nation-wide analyses. PAHO will analyze regional information to determine the impact of influenza outbreaks and to contribute to the evaluation and implementation of disease-control interventions.
1. Influenza-like illness (ILI) is used by Sentinel Clinics. ILI is defined according to WHO criteria (27): Sudden onset of a fever over 38C, AND Cough or sore throat, AND An absence of other diagnoses.
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2. Severe Acute Respiratory Infections (SARI) is used by Sentinel Hospitals and as part of Nationwide Surveillance. The definition for SARI is adapted from the WHO protocol on rapid response (28). For persons 5 years old: Sudden onset of fever over 38C, AND Cough or sore throat, AND Shortness of breath or difficulty breathing, AND Requiring hospital admission The SARI definition for children <5 years old is adapted from the program for Integrated Management of Childhood Illness (29): Any child <5 years old clinically suspected of having Pneumonia or Severe/very Severe Pneumonia (see annex), and requiring hospital admission. A confirmed case of influenza is defined as any case with laboratory test results positive for influenza virus.
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Substantial data regarding the epidemiology and burden of viral respiratory infections can be obtained from a minimal number of well-run Sentinel Clinics. It is recommended that a country prioritize the collection of quality surveillance data from a minimal number of Sentinel Clinics over the early implementation of numerous sites. Adequate piloting and evaluation should be performed before any new Sentinel Clinics are added.
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to comply with this last criterion, its specimens should be processed by a different laboratory with appropriately trained staff or by the National Reference Laboratory. The Sentinel Site should have its own coordinator, preferably the person overseeing hospital epidemiology or a representative of the local or Intermediate Epidemiology Office. The Sentinel Site should have the capacity and staff to obtain patient samples at the Sentinel Hospital or Sentinel Clinic and be capable of processing them.
Monitor system implementation Collect data in a timely fashion Process, analyze, and report the data at the local level, integrating laboratory results Make weekly reports to the intermediate or national level.
Record SARI or ILI cases by age group using standardized data collection forms, including any cases of SARI associated deaths. Obtain and transport respiratory specimens according to established criteria and complete the data collection forms.
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Process respiratory specimens for influenza A and B and other respiratory viruses (adenovirus, parainfluenza, and respiratory syncytial virus), by immunofluorescence testing under adequate biosafety conditions as defined by WHO. Communicate laboratory results in a timely manner to the originating practitioner. Make weekly reports of test results to the Epidemiology Office (local or intermediate, depending on the organization of the sentinel unit) and to the National Reference Laboratory. Send all specimens with results positive for influenza and a proportion of negative results to the National Reference Laboratory for further testing.
Provide support to the surveillance system under its responsibility Train hospital and outpatient health care staff. Consolidate and analyze information from the Sentinel Sites under its responsibility. Make influenza epidemiologic situation reports to local and national authorities on a regular basis. Ensure the proper collection of patient information and clinical samples at Sentinel Sites and ensure that samples are properly transported to the National Reference Laboratory.
Coordinate the implementation of the surveillance system. Provide resources for operation of the system. Consolidate information forwarded from the intermediate levels. Analyze information on the weekly epidemiologic situation Set up national and international public health alerts in the event of influenza outbreaks or other situations of concern. Disseminate information and results via periodic reports (e.g., e-mail, website, periodic epidemiologic bulletins) to the public, the surveillance system, and stakeholders
It is recommended that the National Epidemiology Office define strategies (e.g., training, certificates of appreciation, periodic reminders) to stimulate and reinforce the effective operation of the system at the local and intermediate levels.
National Reference Laboratory
Train and supervise surveillance laboratories in immunofluorescence testing and in biosafety practices. Isolate and characterize influenza virus from positive samples according to WHO-defined biosafety conditions Evaluate a percentage of negative samples sent by the local level. Isolate and characterize novel viruses.
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Consolidate and analyze national laboratory data and prepare reports on a weekly basis. Send virologic surveillance reports to Sentinel Sites, states or provinces, and to the Ministry of Health. Report results to PAHO/WHO via FluNet.
5. 8. Implementation
The implementation of surveillance is a responsibility of the national level of public health, in conjunction with the intermediate and local levels, and will depend on the public health organization in each country. The number of persons under surveillance will depend on the number of Sentinel Hospitals and Sentinel Clinics and the size of their patient populations. Prior to surveillance implementation, the total number of weekly admissions during the prior year for pneumonia and influenza should be determined by chart review. This will aid in the determination of the systematic sampling strategy and will provide a SARI baseline estimate. The number of patients sampled for laboratory testing will depend on the Surveillance Laboratorys ability to process, test, and ship specimens; the number of epidemiologists who can oversee data collection and analysis; and the method by which cases are chosen for testing. In general, broad population coverage by the surveillance system is less important than the efficient collection of quality data by a few Sentinel Hospitals and Sentinel Clinics. Consideration should be given to resources needed for the operation of Sentinel Hospitals and Sentinel Clinics, including necessary training, evaluation, and supervision. Health care staff should have training in the use of case definitions and data collection forms, epidemiologic information flow, and sample collection and transport. The National Reference Laboratory will train surveillance laboratories in immunofluorescence testing and biosafety measures. The Laboratory should coordinate with the national level regarding required supplies and human resources. PAHO/WHO and CDC will provide support for national-level training workshops.
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forms provided for collecting aggregate data on ILI and SARI cases. Depending on a countrys ability to collect data, optional information (e.g., sex of the patient) may be reported to the Epidemiology Office.
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Taking a sample within 72 hours after onset of symptoms will improve the accuracy of immunofluorescence. The frequency of false negative immunofluorescence tests will increase over the course of influenza infection as viral shedding decreases. A case that has any Nationwide Surveillance investigation trigger will be counted, but must initiate outbreak response mechanisms outlined in Section 6. Evaluation of such cases will be according to Nationwide Surveillance protocols. If a case is chosen for testing by the systematic sampling process, but that case does not meet the sampling criteria, the patient declines testing, or the patient is not tested for any other reason, the next patient with SARI or ILI should be tested. 5.10.2. Sampling Logistics It is recommended that any cases that meet the sampling criteria defined above have clinical specimens taken as soon as possible during the course of their hospitalization. This may occur when they are assessed for admission in an emergency room or after their admission to the hospital. Ambulatory cases that meet these sampling criteria should have clinical specimens taken while they are still in the Sentinel Clinic. Samples from ILI and SARI cases will be taken by doctors or trained medical personnel, in accordance with the procedures established in each country. In cases involving ILI, a nasal swab should be taken from adults, and for children under five a nasopharyngeal swab or aspirate is recommended. For SARI cases, a nasopharyngeal swab or aspirate is recommended. These specimens should be kept refrigerated in transport media and should be sent as soon as possible to the Sentinel Laboratory along with the data collection form. Commercial transport media or media developed at the lab can be used in accordance with WHO guidelines (see Annex 2). At the Surveillance Laboratory, specimens testing positive for the influenza virus should be stored in transport media at a temperature of 4C and sent within one week to the National Reference Laboratory. 5.10.3. Processing and Testing Specimens will be processed and tested at the Surveillance laboratory for the presence of viral antigens (Adenovirus, Influenza A and B, Parainfluenza, and Respiratory syncytial virus) using the Immunofluorescence Antibody test. Ideally, this technique should be carried out using Biosafety Level 2 (BSL2) practices (30). However, in suspected cases of avian influenza, unusual or unexpected cases or outbreaks of ILI/SARI, they should be processed under BSL2 conditions, using Biosafety Level 3 (BSL3) practices, at the National Reference Laboratory (31).
Specimen Flow at Surveillance Laboratories
Optimally, all of the specimens testing positive for influenza will be sent to the National Reference Laboratory within one week for confirmation and further analyses. If this is not
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feasible, through agreement with the National Reference Laboratory, a representative sample of the positive laboratory tests can be sent for further testing. There may be times during epidemic periods when the National Reference Laboratory is unable to process all positive specimens. In these instances, a majority of positive specimens should be randomly chosen and sent to the National Reference Laboratory Among specimens testing negative for influenza, 10% should be randomly chosen monthly for confirmation by the National Reference Laboratory. During epidemics a representative sample may be processed if the capacity of the National Reference Laboratory is exceeded.
Isolate/Specimen Flow at the National Reference Laboratory
The National Reference Laboratory should perform preliminary antigenic and, if possible, genetic characterization on the virus isolates grown at the facility. The National Reference Laboratory should then send representative virus isolates and lowreacting viruses to the CDC WHO Collaborating Centers for Influenza at least once a month during the surveillance period. If any viruses cannot be subtyped using the WHO reagent kit, the National Reference Laboratory should notify WHO and CDC and immediately send the virus isolate to the CDC WHO Collaborating Centers for Influenza for analysis.
Sentinel Hospital surveillance analyses by epidemiologic week Proportion of SARI cases per total hospitalizations
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Proportion of SARI cases per total hospitalizations by age category If possible, population-based incidence of SARI in aggregate and by age category (when size of service population is known) Proportion of SARI cases testing positive for influenza and other respiratory viruses per the total number of cases tested Proportion of deaths among SARI cases per the total number of hospitalizations. Proportion of deaths among SARI cases per the total number of hospital deaths If possible, population-based incidence of SARI associated deaths in aggregate and by age category (when size of service population is known)
Based on information from five years of surveillance, weekly baselines can be calculated for the above analyses. In the case of the proportion of SARI associated hospitalizations and deaths, baselines can be determined using retrospective information from hospital records. Comparison with previous years using mobile averages can also be performed. These data will aid in the determination of influenza seasonality. Intermediate level data analysis will depend on the number of Sentinel Sites within an area of responsibility. Such data analysis will be consolidations of all Sentinel Site data according to the same parameters as those outlined for local-level data analysis. National-level data analysis will use the same parameters as local-level data but may include consolidation of all collected data and the comparison of data collected by intermediate- and local-levels. Analysis will assess the burden of disease on the national health care system and characterize disease rates across the country. National data consolidation will permit comparisons between countries as well as for an assessment of regional trends throughout the PAHO coverage area.
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The process and outcome indicators are presented in the following table and will allow for system evaluation in accordance with the specific objectives of the Sentinel Surveillance system: Specific Objectives
Determine weekly proportions of ILI among clinic visits Provide epidemiologic and clinical characteristics of confirmed Influenza cases among ambulatory patients with ILI and those hospitalized with SARI Determine the proportion of cases of influenza and other select respiratory viruses confirmed as positive among all ILI and SARI cases.
Process Indicators
Outcome Indicators
Number of ILI case reports made within one Number of ILI case reports made week per number of surveillance weeks. Goal (including zero reports) per number of >80% surveillance weeks. Goal >95% Number of ILI and SARI cases sampled for testing per number of ILI and SARI cases counted. Goal for ILI cases >2%. Goal for SARI cases >50% Number of ILI and SARI cases sampled for testing that has a completed clinical-epidemiologic form per number of ILI and SARI cases sampled for testing. Goal >80% Number of samples tested for ILI and SARI cases per total number of samples taken. Goal >95% Number of samples with positive test results per total number of samples taken Number of weekly laboratory reports per number of surveillance weeks. Goal >95%
Number of samples taken from SARI cases within one day of hospital admission per total number of samples taken. Goal >80%
Proportion of laboratory reports made within Describe the frequency, one week per number of surveillance weeks. temporal trends, seasonality, Goal >80% and geographical distribution of the influenza virus and other respiratory viruses among samples taken from patients with ILI and SARI Determine the percentage of patients hospitalized who died from SARI out of the total number of those hospitalized Number of SARI associated death reports made within one week per total number of surveillance weeks. Goal >80%
Number of SARI associated death reports (including zero reports) per total number of surveillance weeks. Goal >95%
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Specific Objectives
Process Indicators
Outcome Indicators
Number of characterized viruses sent to CDC per total number of viruses characterized. Goal >50%
Isolation and antigenic Weeks reported to FluNet out of total number of surveillance weeks. Goal >80% characterization of influenza viruses for vaccine selection in the National Influenza Centers and identification of new subtypes the influenza virus Rapid identification of subtypes incapable of being characterized or avian subtype strains, confirmation for speedy provision to WHO Collaborating Center Number of reports to PAHO/WHO made within 48 hours of results on cases where subtyping could not be done or where there are new subtypes per total number of such reports. Goal >80%
Number of reports of test results made within 48 hours by WHO Collaborating Centers of samples shipped for rapid subtyping per total number of samples shipped for rapid subtyping. Goal >80%
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Regular reminders, inquiries, and training of reporters will enhance the system and improve system sensitivity. The focus on Nationwide Surveillance should be the investigation and the outbreak response to notifiable events as indicated and defined in the revised International Health Regulations (IHR) and in the WHO pandemic influenza draft protocol for rapid response and containment (28, 32)
6.2. Objectives
Detect outbreaks of SARI in a timely manner Detect cases or outbreaks of ILI or SARI among groups at risk of infection by H5N1 and atypical viruses in a timely manner Detect outbreaks of respiratory infections with pandemic potential in a timely manner Initiate outbreak investigations and implement control measures in a timely manner
Excess Number of SARI Cases An outbreak investigation should be initiated by an increased number of SARI cases over an established threshold, either in a geographically defined area or over a short period of time. The investigation can be initiated anywhere in the country by the existing public health structures.
Clusters of SARI For the purpose of influenza outbreak detection, a cluster is defined as three or more persons geospatially or socially linked with onset of SARI within 10 days of each other (28). Such events may be evidence of efficient and sustained human-to-human transmission of H5N1 or the emergence of a novel respiratory virus.
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Atypical SARI Cases Illnesses that meet the above definitions should be investigated immediately when found among the following: SARI among health care workers or other occupational exposure SARI among travelers to high-risk areas Outbreaks involving two or more family members
Investigation should be initiated prior to laboratory confirmation of etiologic agent. Countries that do not have adequate capacity to establish a probable diagnosis within 48 hours of atypical SARI case identification should request immediate support from WHO. Such events may be evidence of efficient and sustained human-to-human transmission of H5N1 or the emergence of a novel respiratory virus. Unofficial Reported Information Surveillance This involves inquiry into unofficial reports of respiratory infections identified from media reports, the public, professional groups, laboratories, ProMed, or persons in the influenza surveillance network. It may involve a single case, for example, reports of ILI in a poultry worker with contact to suspected H5N1-infected poultry, or an unusual or unexpected outbreak of ILI or SARI. Unofficial reported information surveillance has been shown to be an important aspect of surveillance in recent cases of Avian Influenza A/H5N1 in Southeast Asia (33). Suspected human cases of influenza related to animal exposure To date, cases of human infection with the avian influenza A viruses have been sporadic and rare events, even in areas where the virus is widespread among poultry. Any transition in the behavior and epidemiology of the currently circulating virus may indicate increased transmissibility between humans and will most likely result in an event sufficiently unusual to be detected by alert clinicians or by the public health system. Suspected human cases of influenza related to animal exposure include situations where at least one case with ILI or SARI exhibits a history strongly suggesting potential exposure to the avian influenza A virus, within seven days prior to symptom onset, such as: Travel to or residence in an area affected by influenza outbreaks in birds or other animals. Direct contact with dead or diseased birds or other animals in an affected area. Close contact with human cases of avian influenza virus infection (living or deceased) or with a person who has unexplained SARI. Cases involving possible occupational exposure, including employment as an animal culler, veterinarian, laboratory worker, or health care worker
In an effort to capture novel emerging infections in addition to potential H5N1 virus infection, these criteria are intentionally broader than existing WHO reporting criteria for suspected human cases of H5N1 virus infection (34).
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Additionally, surveillance system staff should make regular reminders of notifiable events to potential reporters and inquire about cases meeting notification triggers that may have gone unreported.
A local inquiry may be all that is necessary if a reported case is of low severity without clinical or epidemiologic features associated with avian influenza or other novel viral infections. RRT investigation may be initiated if there are epidemiologic or clinical characteristics associated with novel virus infections. For example, a local investigation would be appropriate for a primary school outbreak of mild, febrile respiratory illness without recent travel or exposure to sick animals. A RRT investigation would be appropriate for an outbreak of a febrile respiratory disease among poultry workers with exposure to sick birds.
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National Level Integrate outbreak information at the national level. Ensure coordination with other actors involved in the outbreak (laboratory, environmental health, animal health). Provide technical support to outbreak investigation and assure the implementation of control measures. Coordinate with the National IHR focal point. Alert the national network of the outbreak. Make recommendations for corrective measures and follow up their implementation once the outbreak has been controlled. Support RRT equipment and training
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The process and outcome indicators are presented in the following table and will allow for system evaluation in accordance with the specific objectives of Nationwide Surveillance:
Specific Objectives
Timely detection of unusual or unexpected SARI outbreaks. Investigation by the health care system of any reports of unusual or unexpected cases of SARI stemming from any source and, when appropriate, as well as initiation of outbreak investigations. Timely detection and verification of ILI or SARI outbreaks in groups at risk of infection by the avian influence virus or by emerging viruses. Timely detection of outbreaks of viruses of pandemic potential.
Process Indicators
Number of SARI outbreaks reported within 48 hours of onset per total number of outbreaks investigated.
Outcome Indicators
Number of SARI outbreaks verified per total number of SARI alerts made.
Number of SARI outbreaks investigated within 48 hours of onset per total number of outbreaks investigated.
Number of outbreaks investigated per total number of outbreaks reported. Goal >90%
Number of SARI outbreaks investigated where control measures were recommended within 48 hours of onset per total number of outbreaks investigated.
Number of SARI outbreaks investigated where control measures were taken within 48 hours of onset per total number of outbreaks investigated.
8. References
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1. World Health Organization. Resolution WHA 58.3: Revision of the International Health Regulations. [cited 22 November 2006], from http://www.who.int/ipcs/publications/wha/ihr_resolution.pdf 2. World Health Organization. Resolution WHA 58.5: Strengthening Pandemic Influenza Preparedness and Response. 2005 3. World Health Organization. Resolution WHA 59.2: Application of the International Health Regulations. 2005 4. World Health Organization. WHO Influenza Laboratory Guidelines. Vol. 2006. Geneva, Switzerland: World Health Organization, in press 5. Harper S, Klimov A, Uyeki T and Fukuda K. Influenza. Clin Lab Med 2002;22:863-82, vi 6. Heyman D. Control of Communicable Diseases Manual. 18 ed. Washington, DC: American Public Health Association, 2004 7. Smith NM, S. BJ, Shay DK, Uyeki TM, Cox NJ and A. SR. Prevention and Control of Influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55:1-42 8. World Health Organization. Influenza Fact Sheet. 2003 [cited 21 November 2006], from http://www.who.int/mediacentre/factsheets/fs211/en/index.html 9. Cox NJ, Subbarao K. Influenza. Lancet 1999;354:1277-82 10. Viboud C, Alonso WJ and Simonsen L. Influenza in tropical regions. PLoS Med 2006;3:e89 11. Fouchier RA, Munster V, Wallensten A, Bestebroer TM, Herfst S, Smith D, et al. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from blackheaded gulls. J Virol 2005;79:2814-22 12. Centers for Disease Control and Prevention. Update: influenza activity--United States and worldwide, 2005-06 season, and composition of the 2006-07 influenza vaccine. MMWR Morb Mortal Wkly Rep 2006;55:648-53 13. Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 2005;366:1175-81 14. Bright RA, Shay DK, Shu B, Cox NJ and Klimov AI. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. Jama 2006;295:891-4 15. World Health Organization. Advice on Use of Oseltamivir. 2006 [cited 21 November 2006], from http://www.who.int/csr/disease/avian_influenza/guidelines/useofoseltamivir2006_03_17A.pdf 16. World Health Organization. Ten things you need to know about pandemic influenza. [cited 22 November 2006], from http://www.who.int/csr/disease/influenza/pandemic10things/en/index.html 17. World Organisation for Animal Health (OIE). Update on Avian Influenza in Animals (Type H5) 2006 [cited 4 November 2006], from http://www.oie.int/downld/AVIAN%20INFLUENZA/A_AI-Asia.htm 18. World Health Organization. Situation updates - Avian influenza. 2006 [cited 27 November 2006], from http://www.who.int/csr/disease/avian_influenza/updates/en/index.html 19. World Health Organization. WHO Guidelines for Global influenza surveillance 2004;2006 [cited 22 November 2006], 2006, from http://www.who.int/csr/disease/influenza/influenzanetwork/en/index.html 20. Pan American Health Organization. PAHO Strategic and Operational Plan for Responding to Pandemic Influenza (draft). 2005 [cited 22 November 2006], from http://www.paho.org/English/AD/DPC/CD/vir-flu-PAHO-Plan-9-05.pdf
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21. Ministerio de Salud GdC. Sistema de Vigilancia Centinela de Influenza. 2002 [cited 15 December 2006], from http://epi.minsal.cl/epi/html/normas/circul/sist-vig-influ.pdf 22. Ministry of Health and Environment of the Nation. Epidemiological Bulletin. 2005 [cited 21 November 2006], from http://www.msal.gov.ar/htm/site/sala_situacion/PANELES/boletines/boletin_23-2005.pdf 23. Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005;352:333-40 24. Ministry of Health of Chile. Influenza Surveillance System in Chile. 2002 [cited 21 November 2006], from http://epi.minsal.cl/epi/html/frames/frame8.htm 25. Uez O, Savy V, Cordeiro OR, Del Mnaco R, Fidani JL and Rolla MN. Implementacin de Unidades Centinela de Influenza [Spanish]: Argentina Ministry of Health and Environment of the Nation, 2002 26. World Health Organization. Resolution WHA 58.3: Revision of the International Health Regulations. 2005 [cited 15 December 2006], from http://www.who.int/csr/ihr/IHRWHA58_3en.pdf 27. World Health Organization. WHO Recommended Surveillance Standards. Second edition. 1999;2006 [cited 27 November 2006], 2006, from http://www.who.int/csr/resources/publications/surveillance/WHO_CDS_CSR_ISR_99_2_EN/en/ 28. World Health Organization. WHO pandemic influenza draft protocol for rapid response and containment. 2006;2006 [cited 27 November 2006], 2006, from http://www.who.int/csr/disease/avian_influenza/guidelines/draftprotocol/en/index.html 29. World Health Organization. Chapter 7: Cough or Difficulty Breathing. Handbook IMCI Integrated management of childhood illness. Geneva, Switzerland: World Heatlh Organization, 2005:23 30. World Health Organization. Manual de Bioseguridad en el Laboratorio (3rd ed.). 2005 [cited 27 November 2006], from http://www.who.int/csr/resources/publications/biosafety/CDS_CSR_LYO_2004_11SP.pdf 31. World Health Organization. WHO laboratory biosafety guidelines for handling specimens suspected of containing avian influenza A virus. 2005 [cited 27 November 2006], from http://www.who.int/csr/disease/avian_influenza/guidelines/handlingspecimens/en/print.html 32. World Health Organization. Resolution WHA 58.3: Revision of the International Health Regulations. 2005 [cited 21 November 2006], from http://www.who.int/ipcs/publications/wha/ihr_resolution.pdf 33. Samaan G, Patel M, Olowokure B, Roces MC and Oshitani H. Rumor surveillance and avian influenza H5N1. Emerg Infect Dis 2005;11:463-6 34. World Health Organization. WHO case definitions for human infections with influenza A (H5N1) virus. 2006 [cited 27 November 2006], from http://www.who.int/csr/disease/avian_influenza/guidelines/case_definition2006_08_29/en/index. html 35. World Health Organization. Recommended laboratory tests to identify avian influenza A virus in specimens from humans. 2005 [cited 27 November 2006], from http://www.who.int/csr/disease/avian_influenza/guidelines/avian_labtests2.pdf 36. World Health Organization. Collecting, preserving and shipping specimens for the diagnosis of avian influenza A(H5N1) virus infection. Guide for field operations. 2006 [cited 27 November 2006], from http://www.who.int/csr/resources/publications/surveillance/WHO_CDS_EPR_ARO_2006_1/en/i ndex.html
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37. World Health Organization. WHO pandemic influenza draft protocol for rapid response and containment.2006 [cited May 30, 2006], 2006, from http://www.who.int/csr/disease/avian_influenza/guidelines/protocolfinal30_05_06a.pdf 38. World Health Organization. WHO guidelines for investigation of human cases of avian influenza A(H5N1). 2006 [cited 27 November 2006], from http://www.who.int/csr/resources/publications/influenza/WHO_CDS_EPR_GIP_2006_4/en/inde x.html 39. World Health Organization. WHO guidelines for investigation of human cases of avian influenza A (H5N1). 2006 [cited 20 November 2006], from http://www.who.int/csr/disease/avian_influenza/guidelines/en/index.html 40. World Health Organization. WHO Outbreak communication guidelines. 2005;2006 [cited 27 November 2006], 2006, from http://www.who.int/csr/resources/publications/WHO_CDS_2005_28en.pdf
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9. Annexes
Annex 1: Surveillance Data Collection and Flow, Registry Instruments
Data-Collection Responsibilities Those who form the clinical team at the Sentinel Clinic or Hospital should register cases of ILI or SARI by age group on a daily basis and should send the resultant report to the Epidemiology Coordinator once a week. In cases where health care providers use their own registry instruments, the Coordinator of Epidemiology should collect the data and transfer it to the forms used for its consolidation. In both cases, data should ideally be entered into an electronic database, where the person in charge of local laboratories will also be entering laboratory data. Minimal Data Elements to Be Collected
1. Sentinel Ambulatory Clinics shall minimally record the following data:
Influenza by epidemiologic week Number of ILI consultations by age group Number of consultations by age group Number of individuals tested for respiratory viruses by age group, linked to medical record / surveillance number.
Influenza by epidemiologic week Number of patients admitted who have received care for SARI by age group Number of admissions by age group Number of patients who died from SARI by age group Number of individuals tested for respiratory viruses by age group, linked to medical record / surveillance number.
3. Sentinel Ambulatory Clinics and Hospitals shall additionally record the following data for all individuals tested for respiratory viruses:
Hospital / ambulatory clinic data o Patients name o Patients age o Patients sex o Medical record / surveillance number o Date of onset o Date of sampling o Vaccination status during a given time period o Travel information o Contact with disease and/or outbreak (community or institutional) o Treatment provided
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Clinical data
Number and type of viruses detected in ambulatory patients per epidemiologic week by age group and linked to medical record / surveillance number Number and type of viruses detected in hospitalized patients per epidemiologic week by age group and linked to medical record / surveillance number Number of specimens received from Sentinel Clinics, linked to medical record / surveillance number Number of specimens received from Sentinel Hospitals, linked to medical record / surveillance number
5. Surveillance Laboratory shall minimally record the following data elements for each respiratory specimen received:
Medical record / surveillance number Specimen date Patients age Patients city, state or province of origin
6. Reference Laboratories shall minimally record the following data elements for each respiratory specimen received:
Laboratory number Specimen date Patients age Patients city, state or province of origin Type
Information Generated by the National Reference Laboratory Laboratory number Specimen date Patients age Patients city, state or province of origin Isolation system Type Subtype Isolate designation Similarity to reference strain (Yes/No) Whether further identification is in progress (Yes/No) Dissemination of Data Collected from the Influenza Surveillance System
The Local Epidemiology Office shall disseminate the following information to Sentinel Clinics and Hospitals, staff in surveillance offices, and the Surveillance Laboratory on a weekly basis:
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Number of new cases of SARI and total number of hospitalized cases Number of deaths from SARI and total number of all hospitalized or deceased cases Number of hospitalized cases where samples have been sent for laboratory testing Number of cases in clinics where samples have been sent for laboratory testing Number of laboratory tests among SARI cases with positive results Number of laboratory tests among ILI cases with positive results
The Intermediate Level Epidemiology Office will disseminate the following information to all Sentinel Sites located within the state/province, on a weekly basis:
Aggregate the number of new cases of ILI and the total number of patient consultations in clinics within the state/province. Aggregate the number of new cases of SARI and the total number of hospitalized cases within the state/province. Aggregate the number of deaths from SARI and the total number of all patients hospitalized or deceased cases within the state/province. Aggregate the number of hospitalized cases where samples have been sent for laboratory testing within the state/province. Aggregate number of cases in clinics where samples have been sent for laboratory testing within the state/province Aggregate the number of laboratory tests among SARI cases with positive results within the state/province. Aggregate the number of laboratory tests among ILI cases with positive results within the state/province.
Consolidate and analyze all national data. Prepare weekly reports based on national surveillance data, to be periodically disseminated in accordance with existing processes, e.g. via fax, e-mail, Internet, bulletins, or other methods. At least every week, send a report to each level of the surveillance system, using the most expeditious means possible.
Report on the characterization of the influenza viruses received from each local laboratory. Consolidate the information received from these laboratories at the regional or national level.
Registry Instrument We recommend using a form to record this information, ideally directly into a computer or onto a computational system spreadsheet.
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When filling out this form, the customary care registries are to be used where health care providers have recorded cases of a patients initial consultation for ILI. Every week total figures will be compiled for consultations from all causes. Additionally recorded will be the number of cases where diagnostic care was provided by age group (under 6 months, 623 months, 24 years, 514 years, 1549 years, 5064 years, and over 65 years of age) and by epidemiologic weekin addition to the total number of cases where comprehensive care has been provided out of the total number of cases involving care.
2. Weekly Collection Form for Aggregate SARI Case Data
When filling out the form, customary care registries are to be used where health care providers have recorded cases of hospitalization for SARI. Every week total figures will be compiled for hospitalizations from all causes. The number of cases where diagnostic care was provided will be recorded by age group (under 6 months, 623 months, 24 years, 514 years, 1549 years, 5064 years, and over 65 years of age) and by epidemiologic weekin addition to the total number of cases of where comprehensive care has been provided out of the total number of cases involving care.
3. Weekly Collection Form for Fatal SARI Cases
When filling out the form, death certificates will be used where health care providers have registered the primary cause as death by SARI. The number of deaths will be recorded by diagnosis and age group (under 6 months, 623 months, 24 years, 514 years, 1549 years, 5064 years, and over 65 years of age), as well as epidemiologic week.
4. Epidemiologic Data Form for ILI and SARI Cases and Sample Shipment (Clinical Epidemiologic Record)
For cases studied utilizing respiratory samples, we recommend using a specific form, ideally a spreadsheet that is part of a computerized system. Baseline data will be included for identification (patients name, age, sex, and record number), date of sampling, clinical and epidemiologic data (previous vaccinations, isolated case or [community or institutional] outbreak, and treatment). This form will make it possible to describe detected cases of influenza and other respiratory viruses in epidemiologic terms. The latter should be used when sending the sample to the laboratory.
5. Form for Reporting Weekly Laboratory Results from ILI and SARI Cases
The laboratory will individually report to hospital services the results of any samples they send out. The laboratory will make weekly reports on the number of cases and specimens tested, on positive cases by age, and on the number of negative cases. This report will be sent to the Epidemiology Coordinator using the Laboratory Results Form. The laboratory can also add the distribution of the number of samples by age group in order to monitor the representation of all age groups.
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Under 6 months
Total Visits # ILI
623 months
Total Visits # ILI
Under 2
Total Visits # ILI
2-4 years
Total Visits # ILI
5-14 years
Total Visits # ILI
15-49 years
Total Visits # ILI
50-64 years
Total Visits # ILI
Over 65
Total Visits # ILI
Monday Tuesday Wednesday Thursday Friday Saturday Sunday Total for Week Population Incidence Rate (per 100,000)
Surveillance Coordinator:
Signature
15 December 2006
Weekly Data Collection Form for Severe Acute Respiratory Infection (SARI) Hospitalizations
Health Service, Department of Health, Region Sentinel Hospital Epidemiologic Week # Date of Report
Under 6 months
Total hospitalized # SARI
623 months
Total hospitalized # SARI
24 years
Total hospitalized # SARI
514 years
Total hospitalized # SARI
1549 years
Total hospitalized # SARI
5064 years
Total hospitalized # SARI
Over 65
Total hospitalized # SARI
Surveillance Coordinator:
Signature
37
15 December 2006
Under 6 months
623 months
24 years
514 years
1549 years
5064 years
Over 65
# dead from # dead from # dead from # dead from # dead from # dead from # dead from # dead from Total # dead Total # dead Total # dead Total # dead Total # dead Total # dead Total # dead SARI SARI SARI SARI SARI SARI SARI SARI
Surveillance Coordinator:
Signature:
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ILI
SARI
..............................................................
Case ID #.................................................................................................................................. Last Name, First Name............................................................................................................. Date of Birth: ....../....../....................... Age: .......................... Sex:....................
Date of Onset of Illness: ....../....../.............. Epidemiologic Week # .............................. Date Sample Taken: ....../....../............. Flu Shot: Yes No Date of Vaccination: ......../........./................
Clinical Profile
Yes Fever over 38C Rhinorrhea Pharyngitis Conjuntivitis Otitis Bronchitis Bronchiolitis Pneumonia Cough Shortness of Breath No Adenopathies Asthenia Headaches Myalgia Vomiting Diarrhea Rashes Sporadic case Symptom onset during outbreak Yes No
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Total SARI
24 years SARI
Over 65 SARI
Total ILI
24 years ILI
Over 65 ILI
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o o o o
Nasopharyngeal aspiration kit Test tube rack, ice bath Vacuum pump Container with disinfectant solution
Method
o Break open the envelope containing the aspiration kit and connect the end of the tube that is smaller in diameter to the aspiration tube. o Connect the other end of greater diameter to the vacuum pump. o Insert the feeding tube to the patients nostril. o Remove the tube by rotating it smoothly, then repeat the procedure with the other nostril. o Aspirate a volume of about 810 ml of cold tampon solution, pH 7.2, through the collector tube to drag out the whole secretion. o Change the cover of the collector tube and identify it with the patients data. o Send the sample to the laboratory immediately, along with the sample shipment form, ensuring that it remains in an ice bath until the time of its arrival at the laboratory.
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General signs of danger: o o o o Child unable to drink or be breastfeed Child is lethargic or unconscious. Child vomits everything Convulsions
Difficult breathing:
o If the child is: 2 months up to 12 months Fast breathing is: 50 breaths per minute or more o the child is: 12 months up to 5 years Fast breathing is: 40 breaths per minute or more)
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