Measles Surveillance in the United States: An Overview

SUPPLEMENT ARTICLE Measles Surveillance in the United States: An Overview Dalya Güriş, Rafael Harpaz, Susan B. Redd, Natalie J. Smith, a and Mark J. Papania National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia The elimination of endemic measles from the United States has been a national goal since the introduction of measles vaccine, and measles surveillance has been crucial to guide the elimination efforts. The United States surveillance system is geared towards detection of measles virus transmission, rapid discovery of measles outbreaks to facilitate outbreak control, and identification of risk factors for measles. The surveillance system is a passive reporting system that, when activated by a reported case of suspected measles, triggers a search for additional cases around the reported case. Cases are typically reported by health care providers or from schools and day care centers. The sensitivity of the system is increased through reporting and investigation of all suspected measles cases by means of an inclusive case definition (generalized maculopapular rash and fever), and the specificity is increased through laboratory testing for measles of all suspected cases. The purpose of measles surveillance in the United States is to detect measles virus transmission, to discover measles outbreaks quickly to facilitate outbreak control, and to identify risk factors for measles. The information gained from measles surveillance is used to develop measles prevention strategies and to evaluate the impact of these strategies. The system has evolved gradually with the changes in the epidemiology of measles and the national strategies and goals. In the United States, reporting of measles cases to the US Public Health Service started in 1912, and by the mid-1920s, all states participated in the reporting. In the early 1900s, surveillance data documented the health burden of measles, with thousands of deaths and hundreds of thousands of cases reported each year [1]. There was a sharp decline in the case fatality rate for measles through the 1950s, which resulted in reported deaths decreasing to hundreds per year, although incidence was not decreased [2]. Early surveillance also described the age distribution of measles, the geoa Deceased. Reprints or correspondence: Dr. Dalya Güriş, Centers for Disease Control and Prevention, 1600 Clifton Rd., Mailstop E-05, Atlanta, GA 30333 (dhm5@cdc.gov). The Journal of Infectious Diseases 2004; 189(Suppl 1):S177 84 This article is in the public domain, and no copyright is claimed. 0022-1899/2004/18909S1-0027 graphic distribution, and the epidemic cycles. Although it is estimated that only 10% of actual measles cases were reported, the system was adequate to perform the above tasks. With the advent of the measles vaccine era in 1963, measles surveillance demonstrated the tremendous impact of vaccination programs, with a 95% decrease in reported measles cases by 1968 [1]. A cyclic pattern of measles resurgences was shown by the surveillance data over the next decades, with epidemic peaks much smaller and farther apart in time than the patterns seen in the prevaccine era. The elimination of endemic measles from the United States has been a national goal since the successful introduction of measles vaccine. Measles surveillance has been crucial to guide the elimination efforts. Surveillance data have been used to assess the adequacy of measles vaccination policies and the effectiveness of program implementation. The objectives of the current measles surveillance are as follows: to detect cases and small chains of transmission to prevent them from becoming larger outbreaks; to detect imported cases of measles to prevent indigenous spread; and to help document progress toward measles elimination objectives. Herein, we describe the current US measles surveillance system structure and functions. We discuss briefly the major Measles Surveillance in the United States JID 2004:189 (Suppl 1) S177

Figure 1. Measles surveillance in the United States. CDC, Centers for Disease Control and Prevention; EPO, Expanded Programme on Immunization (World Health Organization); NCID, National Center for Infectious Diseases; NIP, National Immunization Program. strengths and weaknesses of the system. Other articles in this supplement will describe more detailed assessment of the adequacy of the measles surveillance system to meet these objectives. MEASLES SURVEILLANCE: A RESPONSIVE SURVEILLANCE SYSTEM The surveillance system in the United States is a passive reporting system that, when activated by a reported case of suspected measles, triggers a search of additional cases around the reported case. On receipt of a case report, surveillance staff investigate the reported case and undertake active case finding among persons who may have infected the reported case patient or been infected by the case patient. Some health departments, such as the New York Urban Area Department of Health and the Houston Department of Health and Human Services, routinely conduct active surveillance for measles, even in the absence of previously identified cases [3]. MEASLES SURVEILLANCE: CASE DEFINITIONS AND CLASSIFICATION Clinical case definition. The following case definition for measles has been approved by the Council of State and Territorial Epidemiologists [4]. A clinical case is an illness characterized by all of the following: a generalized maculopapular rash lasting for 3 days; a temperature of 38.3 C; and at least 1 of cough, coryza, or conjunctivitis. Laboratory criteria for diagnosis. Laboratory criteria for diagnosis include the following: a positive result of serological testing for measles IgM antibody, or a significant increase in measles antibody level by any standard serological assay, or isolation of measles virus from a clinical specimen. Case classification. Cases are classified as follows. A suspected case is febrile illness accompanied by generalized maculopapular rash; a probable case is one that meets the clinical case definition, has noncontributory or no serological or virological testing, and is not epidemiologically linked to a confirmed case; a confirmed case is one that is laboratory-confirmed or that meets the clinical case definition and is epidemiologically linked to a confirmed case. A laboratory-confirmed case does not need to meet the clinical case definition. In addition, cases are classified according to the source of infection [5]. Measles cases among persons whose rash occurs within 21 days after entering the United States and whose illness cannot be linked to local transmission are classified as internationally imported cases. Cases among persons who were infected in the United States are classified as indigenous measles cases. Indigenous cases are subclassified into 3 groups: cases epidemiologically linked to importation cases that are part of a chain of transmission initiated by an internationally imported S178 JID 2004:189 (Suppl 1) Güriş etal.

Figure 2. Measles case investigation and classification flow chart. Epi-linked, epidemiologically linked. case; imported virus cases cases that are part of a chain of transmission from which an imported measles virus strain was isolated (i.e., virus with genotype not known to circulate in the United States), but a link to an internationally imported case was not identified (i.e., no travel history); and unknown-source cases no epidemiological or virological association to importation detected. Internationally imported cases, cases epidemiologically linked to importation, and imported virus cases are all considered importation-associated cases. A chain of transmission is a group of cases that are linked to each other epidemiologically. MEASLES SURVEILLANCE: THE BASIC STEPS Step 1. Patient or Parent Seeking Medical Care The first step in detection of a measles case is for the patient or the patient s parent to seek medical care (figure 1). The factors involved in the decision to seek medical care may include having health insurance, economic status of the family, or perceived severity of the disease. International visitors may be less likely to seek health care; they may be in the United States for a short period of time, may not be familiar with the health care system in the United States, or may not have appropriate documents for being in the United States. Unless the patient comes to medical attention, the case is unlikely to be reported. However, there are several alternative pathways to detection of the case. Occasionally an astute parent or patient may contact the health department directly. The staff at a school or day care center may note a patient s rash and fever and report the case directly to the health department. Rarely, airline attendants have noted rash and fever in passengers and reported the case. Finally, a case of measles in a patient who has not sought medical care may be detected through the health department s investigation of another case. Step 2. Health Care Provider Suspects Measles The second step in measles surveillance is for the health care provider to suspect measles in a patient with rash and fever. Most physicians in the United States have never seen a case of measles or have not seen a case in recent decades. The vast majority of patients with rash and fever seen by providers do not have measles, and it would be very difficult to identify the true measles cases on a clinical basis. Therefore, the current case classification system is intended to support a high index Measles Surveillance in the United States JID 2004:189 (Suppl 1) S179

Figure 3. Example of a measles case investigation and report form (source: California Department of Health Services) S180

Figure 3. (Continued.) S181

of suspicion of measles among providers and to rely on laboratory tests for confirming the specific diagnosis. Step 3. Health Care Provider Reports Suspected Measles Case to the Local Health Department All 50 states require health care providers to report measles cases to the appropriate local or state health department [6]. Some states also require reporting by hospitals, schools, clinical laboratories, or other facilities. Surveillance guidelines generally indicate that measles should be reported immediately or within 24 h of detection. However, in practice there are generally no fines or penalties for delayed reporting or failing to report. Step 4. Case Investigation Phase 1: health care provider and health department confirm the diagnosis. The next step in measles surveillance is investigation of the suspected case. The responsibility for case investigation typically rests in the local health department, although state health departments often assist in case investigations, especially in outbreak settings. In some jurisdictions, responsibility for case investigations belongs to state health departments. Suspected measles cases should be investigated immediately [7]. A flow chart depicting case investigation and classification appears in figure 2. Case investigation is conducted by use of standard case investigation forms (an example is shown in figure 3). Although case investigation forms may vary among the states, all programs collect data about a series of key variables. Identification and demographic information is collected to allow for case identification, location of the case patient in the future, and analysis of possible risk factors for disease. The clinical details (symptoms, including their description, onset date, and duration) are reviewed to determine whether the patient meets the criteria for a suspected measles case and warrants further investigation. A blood sample is collected, if not yet obtained by the health care provider. Laboratory confirmation is recommended for all cases. Although providers often collect the serum specimen, it is recommended that reporting the case to the health department not be delayed while awaiting laboratory results. On initial contact with the suspected case, health care providers and staff of health departments are also encouraged to collect a clinical specimen (urine sample, nasopharyngeal or throat swab) for virus isolation and genotypic characterization. Laboratory confirmation is primarily done by serological testing (figure 2). Tests that yield negative results within the first 72 h after rash onset should be repeated with a serum sample collected 172 h after rash onset. Clinical specimens for virus isolation should ideally be collected within 7 days of rash onset and should not be collected if 110 days have passed after rash onset. The laboratory information (serological results, date of specimen collection) is documented on the case investigation form. Rarely, a true sporadic case is discarded when laboratory evidence is absent. If a secondary case occurs that was laboratory-confirmed, the discarded case is reclassified as confirmed. To assess the impact of the vaccination program and evaluate the effectiveness of the vaccine, vaccination status (number of doses and dates of measles vaccination) is assessed. If patients or their parents cannot give a reliable vaccination history, including dates of vaccination, the vaccination provider is contacted for this information. Risk factors for disease (travel, contact with other cases, contact with travelers or immigrants) are assessed to identify potential sources of infection, to evaluate the risk of further spread, and to implement control measures. The outcomes of the measles infection, including complications, hospitalization, or death, are detailed to assist in the monitoring of the burden of disease. Phase 2: contact tracing. A crucial part of the case investigation of a suspected measles case is the identification of persons who may have been in contact with the patient during the time the patient was infected (potential source cases) or during the time the patient was infectious (potential secondary cases). Most case investigation forms include an exposure time line, which assists the investigator in establishing the probable dates of exposure and the infectious period of the case (usually considered 4 days before to 4 days after rash onset). The primary purpose of the contact tracing is to identify and vaccinate exposed persons who may be susceptible to measles. Secondary purposes include identification of additional cases and describing the patterns of transmission of measles. Contacts susceptible to measles are identified and vaccinated through the case investigation process. This may be as simple as vaccinating the unvaccinated sibling of a patient with measles while the surveillance staff is in the home investigating the case or as complicated as carrying out a campaign to vaccinate all of the undervaccinated students in an entire school or school district. In general, simple control measures, such as vaccinating siblings of patients with suspected measles, should not be delayed while awaiting the laboratory confirmation of the cases. However, major control activities, such as vaccinating students in an entire school, may be delayed pending the return of laboratory results. These results should be available as quickly as possible, usually within 24 h. Decisions for control activities are assessed on a case-by-case basis, depending on epidemiological data and on the availability of resources. Susceptible contacts who have a contraindication for measles vaccination (e.g., pregnant women) or are at high risk of severe measles (e.g., patients with AIDS) should be treated with immune globulin to prevent measles or limit the severity of the disease [8]. Health department staff searching for contacts of measles case patients also can identify additional suspected cases of S182 JID 2004:189 (Suppl 1) Güriş etal.

measles. A similar case investigation of each newly identified case is conducted. This process continues until no new cases are discovered. Step 5. The Role of the Laboratory in Measles Surveillance Laboratory testing is a major component of measles surveillance in the United States. In a setting in which true measles cases occur very rarely, the positive predictive value of clinical diagnosis of measles is low and can lead to unnecessary implementation of control measures. Therefore, current measles surveillance guidelines in the United States classify measles cases as confirmed only if confirmed by laboratory tests or epidemiological linkage to a laboratory-confirmed case. Laboratory criteria for diagnosis are as follows: positive results of serological testing for measles IgM antibody, significant increase in measles IgG antibody level by any standard serological assay, or identification of measles virus from a clinical specimen through virus culture or reverse transcriptase polymerase chain reaction. Serum specimens should be tested at either public or private laboratories by means of standard measles diagnostic tests. The test used by the Centers for Disease Control and Prevention (CDC) is IgM capture EIA, which is sensitive, specific, and has rapid performance [9]. This test configuration is now available from commercial vendors. Laboratories are required to report confirmed measles in all but 4 states (Arizona, Illinois, Maryland, and Pennsylvania) [6]. In some states, the state laboratory will routinely test specimens submitted for testing for other rash illnesses, such as rubella, for measles if the test for the suspected illness yields negative results. Also, specimens submitted because of suspected measles are often tested for rubella if the measles test yields negative results. Isolation and genetic sequencing of measles viruses detected in the United States have been very important in documenting the elimination of endemic measles viruses [10]. Urine samples or nasopharyngeal swabs are collected for this purpose. These specimens can be submitted by state health departments to the Measles Laboratory of the National Center for Infectious Diseases, CDC, for genetic sequencing. Step 6. State and National Level Reporting, Data Consolidation, and Analysis State health departments often participate directly in case investigation efforts as described above. Once states have been notified of a measles case, there are 2 basic pathways for state health departments to report to the CDC at the national level. For rapid reporting, cases are reported by telephone. Detailed reporting is done through an electronic reporting system. Rapid reporting of suspected cases under investigation to the CDC by telephone allows immediate notification of other states or countries where the case patient may have traveled during exposure or infectious period. Also, the CDC provides technical assistance with outbreak control and prevention measures, if needed. Although prompt reporting by telephone of all suspected cases is encouraged, only confirmed cases are reported to the National Notifiable Diseases Surveillance System (NNDSS), CDC. Measles is included on a list of conditions approved by the CDC and the Council of State and Territorial Epidemiologists that should be reported to the CDC s NNDSS. Ultimately, however, disease reporting by states to the CDC is voluntary. States report information to the NNDSS through the National Electronic Telecommunications System for Surveillance (NETSS) (figure 1). It is recommended that states submit information to the NETSS within 14 days of the initial report to the state or local health department. This detailed information is used for assessing long-term trends and risk factors for measles. The data have been used to guide measles vaccination policy in the United States. For example, in 1989 a seconddose measles vaccination was included into routine immunization schedule, on the basis of surveillance data from the epidemic of 1988. Step 7. Measles Surveillance Feedback CDC, State, Local Every week the number of cases reported by state health departments is published in the CDC s Morbidity and Mortality Weekly Report (MMWR) (http://www.cdc.gov/mmwr/). These data are provisional, because reports may be delayed or additional information may be gathered that may change the final classification of the case. Updated final reports are published annually in the CDC s Summary of Notifiable Diseases, United States. The CDC also routinely publishes a measles update that is distributed by mail, fax, or e-mail to all state health departments and to other interested parties. The update describes details of recent measles cases by state. In addition, data relating to measles are disseminated through publication of articles in MMWR, MMWR Surveillance Summaries, and other journals. State and local health departments have newsletters and Web sites to communicate with the local provider community and other relevant parties. CONCLUSION In summary, the US measles surveillance system is a passive reporting system that, when activated by a reported case of suspected measles, triggers a search for additional cases around the reported case. The sensitivity of the system is increased by reporting and investigation of all suspected measles cases by use of a very inclusive case definition (generalized maculopapular rash and fever). The specificity of the system is enhanced via laboratory testing for measles of all suspected case Measles Surveillance in the United States JID 2004:189 (Suppl 1) S183

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