From root@aspensys.com Wed Jun 21 09:39:13 1995 Date: Wed, 21 Jun 1995 12:53:12 +0500 MORBIDITY AND MORTALITY WEEKLY REPORTS Part 3 of 5 ****************************************** Centers for Disease Control and Prevention June 16, 1995 Vol. 44, No. RR-6 Make immediate epidemiologic assistance available. Rapid initiation of epidemiologic investigations might be necessary when disease surveillance or water quality data indicate that the public might be at increased risk for cryptosporidiosis. Although some states and cities could implement such investigations independently, many could not and would need technical and financial assistance. Rapid response teams based at CDC and EPA should be organized so they would be available to respond to such events. These teams also could assist states in responding to outbreaks of cryptosporidiosis. These investigations should emphasize a) assessment of the morbidity and mortality in various immunocompromised populations, b) appropriate and rapid environmental testing for Cryptosporidium oocysts, c) rapid identification and evaluation of potential sources of water contamination (e.g., sewage), and d) a thorough engineering assessment of the water utilityIs equipment and treatment processes. Epidemiologic Study Designs The ICR does not include financial or strategic support for assessing possible health risks that might be associated with the occurrence of small numbers of Cryptosporidium oocysts in source or finished water. Moreover, the ICRIs proposed laboratory method for testing water for Cryptosporidium does not include the recovery efficiency and precision necessary for conducting true dose-response-type studies. For example, the same specimen tested several times by the same laboratory could yield counts ranging from 0 to >=30 oocysts per 100 L of water. Furthermore, laboratories cannot determine reliably whether oocysts that are identified in a specimen are still living and capable of causing disease in humans. (See Work Group IV. Water Sampling Methods and Interpretation of Results.) This work group proposed the following study designs for comparing Cryptosporidium infection in exposed and unexposed groups. These suggestions were based on the assumption that a more reliable test will be available in the future or that studies could be designed without the need to quantify precisely the number of oocysts present in drinking water. Surveys of stool specimens. Studies designed to compare the prevalence of laboratory-confirmed Cryptosporidium in stool samples obtained from two populations (i.e., one group exposed to water contaminated with oocysts and the other group not exposed) or in the same population (i.e., before and after exposure to contaminated municipal drinking water) are difficult to conduct. A demographically similar control group that has not been exposed to contaminated drinking water must be identified, and an adequate number of persons must participate in the study. Because the background prevalence of cryptosporidiosis is expected to be minimal (i.e., 1%-2%) in persons unexposed to contaminated water, large sample sizes are required to detect twofold to fivefold increases in stool positivity rates in the exposed population. The sample size must be large enough to show the statistical validity of a negative result (i.e., to indicate that the health risks are below an established level). For example, if the background Cryptosporidium stool positivity rate is assumed to be 1% in persons not exposed to contaminated water, the sample size required to detect a two-fold increase in prevalence among exposed persons (at a confidence level of 95% and a power of 80%) is 4,500 persons (i.e., 2,250 persons in both the exposed and unex-posed groups). A more manageable sample size of 650 persons is calculated if the detection of a fivefold or greater increase (i.e., an increase from 1% to 5%) in stool positivity is desired. However, negative results from a study using this smaller sample size would not exclude the possibility that exposure to oocysts in the contaminated water resulted in a substantial, but lesser, number of Cryptosporidium infections (e.g., a twofold to threefold increase in the stool positivity rate). Surveys of serologic specimens. Conducting a survey of serologic specimens instead of stool specimens to detect differences in Cryptosporidium antibody prevalence rates in exposed and unexposed populations could facilitate the epidemiologic assessment of health risks attributable to waterborne transmission of oocysts. A reliable assay that could distinguish between previously and recently acquired Cryptosporidium infection would enable investigators to survey relatively large populations, especially if blood already collected for other purposes could be tested. A sample size of 625-750 persons, with 50% of the sample comprising persons exposed to contaminated water and 50% comprising persons not exposed, is needed to demonstrate that a >=10% increase in antibody prevalence in the exposed population is statistically different from the background prevalence in the unexposed population. This sample size is based on the assumption that the prevalence of anti-Cryptosporidium antibody detectable by enzyme-linked immunosorbent assay (ELISA) is 20%-30% in residents of communities that are not exposed to Cryptosporidium in drinking water. Use of a Western blot test or other tests instead of the ELISA for serologic testing could result in a different sample size calculation because of different background rates of seropositivity. High priority should be placed on pilot testing current serologic methods to better define the sensitivity and specificity of these methods for identifying Cryptosporidium infection and to review the extent to which these methods distinguish recently acquired infections from those acquired previously. Case-control studies. Case-control studies are designed to test the association be-tween a given exposure and an infection rather than establish a difference in the actual infection rate as described previously. Case-control studies require that a method be developed to a) identify persons (i.e., case-patients) who have laboratory-confirmed cryptosporidiosis, b) identify one or more groups of uninfected persons (i.e., those in the control group) who are representative of the population from which the case-patients are drawn, and c) identify (by using an epidemiologic questionnaire) the exposures to infection that are more common among case-patients than persons in the control group. Although the exposure of predominant interest is exposure to tap water, the questionnaire must be developed to enable evaluation of the relative contributions of other possible sources of exposure. The case-control study design can assess the sources of exposure to low-incidence diseases; compared with population-based studies described previously, this design usually requires a substantially smaller sample size. To exemplify these sample size requirements, it can be assumed that persons drinking tap water are at greater risk for exposure to Cryptosporidium than persons drinking only specially selected or treated bottled water. As an example, 90% of case-patients in this study design drink tap water (i.e., 10% drink only bottled water), and only 80% of controls drink tap water. A sample size of 438 persons (i.e., 219 case-patients and 219 controls) is needed to demonstrate that this 10% difference in exposure to tap water is unlikely to be caused by chance alone (confidence level=95%, power=80%). Similarly, if 95% of case-patients and 90% of controls drink tap water, the desired sample size would increase to 948 (474 case-patients and 474 controls). In most case-control studies, locating several hundred persons in a community who have laboratory-confirmed cryptosporidiosis is difficult. Theoretically, case-patients can be enrolled in a study even if their diagnosis of cryptosporidiosis was made 1-2 years previously; however, the memories of such patients could be affected by recall bias (i.e., they could have difficulty recalling when or if they had certain types of exposures to Cryptosporidium [e.g., through contaminated recreational water, contact with children who wear diapers, sexual contact, visiting a person who had diarrhea, or brief travel to other cities that have greater risk for waterborne infection]). Recall bias also can affect the memories of persons in control groups; therefore, investigators should strive to enroll in the study those persons whose illness was diagnosed recently. For patients who have AIDS, a recently diagnosed Cryptosporidium infection might not represent a recently acquired infection. A case-control study also can be conducted in communities in which most neighborhoods receive tap water from surface water sources but some neighborhoods receive well water. In this situation, users of well water could be considered unexposed. However, investigators must be able to identify persons who receive well water at their residence but who might work or attend school in an area served by surface water. Such persons should be considered as exposed to Cryptosporidium. Intervention cohort studies. In an intervention cohort (i.e., prospective) study, the researchers a) try to control, either randomly or nonrandomly, who is exposed to tap water from a surface source during a specified time period and b) monitor for the occurrence of cryptosporidiosis in the exposed and unexposed populations. The unexposed group is composed of persons who drink either well water, high-quality bottled water, or adequately filtered water. A major advantage of this study design is that researchers have greater ability to demonstrate whether the exposure is associ-ated with infection or disease. This type of study, however, is not appropriate for the investigation of low-incidence diseases (e.g., communitywide incidence of crypto-sporidiosis) because large sample sizes are needed. Study design summary. The most feasible study design to use when investigating waterborne cryptosporidiosis in nonoutbreak settings might be a cohort study that incorporates a serologic test for rapidly identifying seronegative persons. Two groups (i.e., an exposed and an unexposed group) could be retested 6-12 months after the initial test. Half the cohort of seronegative persons could be given Cryptosporidium-free water to drink, and the other half could drink tap water from a surface source. Alternatively, the cohort could contain persons residing in an area of a larger city in which some residents use municipal surface water and some use a nonsurface water source (e.g., a well). Persons who develop diarrhea could either be screened for Cryp-tosporidium infection by stool examination or evaluated serologically for infection soon after illness, or both tests could be used. Sample size considerations are the same as those for population surveys. Work Group II. Public Health Responses This work group focused on identifying methods and messages for notifying agencies, advocacy groups, and the public of potential risks for waterborne Cryptosporidium transmission and on providing guidance for public health responses when oocysts are detected in drinking water. Boil-Water Advisories A boil-water advisory is a public health measure that, if implemented promptly, can successfully reduce the risk for potentially serious diarrheal and other waterborne diseases among persons whose water supply has been contaminated by microbial pathogens. However, boil-water advisories also might be associated with adverse effects, including economic losses (e.g., increases in energy use and/or losses to the food, beverage, and tourism industries), erosion of public confidence, diversion of public health resources, and burn injuries resulting from unintentional contact with boiling water. These factors and available information regarding the level of risk for cryptosporidiosis in a community must be considered carefully before issuing a boil-water advisory. A task force should develop general guidelines for implementing and lifting boil-water advisories to assist local agencies in deciding when boil-water advisories should be implemented. A balanced approach is recommended. Finding low levels of Cryptosporidium oocysts in finished water should not be the reason for issuing a boil-water notice for the general public, unless the decision is supported by other data that suggest water quality is not acceptable. Supportive information could include raw water turbidity and fecal coliform counts, particle counts or turbidity measurements on individual filters, treatment plant effluent, and epidemiologic information confirming increases in diarrheal disease in the community. Because a low number of oocysts in treated water should not be the only reason for issuing an advisory, the continued presence or absence of oocysts should not be the sole criterion for deciding if municipal water is safe to drink. Information Dissemination and Education Public health officials, water utility officials, health-care providers, immunosup-pressed populations, and the general public should be provided information on Cryptosporidium and drinking water before the ICR is implemented. A task force should be created with representatives from federal, state, and local public health agencies, water treatment utilities, public officials, health-care providers, immunosup-pressed populations, and the general public; the goal of this task force should be to develop and distribute educational materials to explain the relationship between the parasite Cryptosporidium, drinking water, and the ICR. A high priority should be placed on educating immunosuppressed persons, who are at increased risk for severe cryptosporidiosis if they become infected. Immunosuppressed persons should be provided information about how to reduce the risk for cryptosporidiosis, regardless of the source of transmission, and about measures they can take to ensure their drinking water is safe (see Work Group III. Cryptosporidiosis in Immunosuppressed Persons). Before the ICR is implemented, local public health officials and water utility officials should develop coalitions with other groups (e.g., health-care providers and members of advocacy groups for immunosuppressed persons) to discuss the public health im-plications of the ICR. These coalitions should develop plans for communicating important public health information, and they should decide what specific action, if any, will be taken if Cryptosporidium oocysts are detected in municipal water. The coalitions should agree on the criteria for, and logistical issues relevant to, issuance of a public notification or boil-water advisory. Work Group III: Cryptosporidiosis in Immunocompromised Persons No current data indicate that immunocompromised persons are more likely than immunocompetent persons to acquire cryptosporidiosis during waterborne out-breaks. However, immunocompromised persons who have HIV/AIDS, patients receiving treatment for cancer, recipients of organ or bone marrow transplants, and persons who have congenital immunodeficiencies are at greater risk than are immu-nocompetent persons for developing severe, life-threatening cryptosporidiosis if they become infected. Therefore, all immunocompromised persons should be educated and counseled about the ways that Cryptosporidium can be transmitted (e.g., sexual practices involving fecal exposure, contact with infected adults or with infected children who wear diapers, contact with infected animals, drinking or eating contaminated water or food, and exposure to contaminated recreational water).