United States Environmental Protection Agency Health Effects Research Laboratory Research Triangle Park NC 27711 Research and Development EPA-600/S1-84-006 July 1984 &EPA Project Summary Retrospective Epidemiological Study of Disease Associated with Wastewater Utilization Hillel I. Shuval, Badri Fattal, and Yochanan Wax A retrospective* epidemiological study was carried out on the association between enteric disease incidence and wastewater utilization in 79 kibbutzim (cooperative agricultural settlements) in Israel having a population of 32,672. Medical records on disease incidence were collected directly from the patients' files at each kibbutz clinic. These records provided information on 24 de- fined diseases, laboratory confirmed or clinically diagnosed, half of which were enteric diseases which might possibly be transmitted by wastewater, while the other half were non-enteric diseases which served as controls. Environmental data such as the location of the sewage irrigated tracts, wind direction and source of water supply were collected for each kibbutz. The kibbutzim included in the study were divided into four categories: I. Thirty irrigating with wastewater effluent in addition to irrigating with freshwater. Population: 13,531. II. Twenty-eight not utilizing efflu- ent for any purpose, which served as a control group. Population: 11,096. III. Ten using wastewater effluent as feed-water for fish ponds. Popu- lation: 5,005. IV. Eleven which practiced two con- secutive years of effluent utiliza- tion and another two consecutive years in which no effluent was utilized for any purpose or vice versa. Population: 3,040. "Although some authorities prefer the name historical prospective for a study of this design, the term retrospective has been used for purposes of simplicity The risk of enteric disease associated with various forms of effluent utilization was estimated for different age groups using both the logistic and log linear regression models which controlled for various confounding factors including: length of irrigation period, geographic region, source of water supply, source and volume of wastewater, source of clean irrigation water, and population size. The high degree of intra- and inter- kibbutz variations of disease rate in the 68 kibbutzim in categories l-lll resulted in conflicting findings and anomalies which did not provide a basis for drawing conclusions. However, no evidence of excess risk associated with effluent irrigation was found. In the switch category (IV) a clearly significant excess risk of total enteric disease ranging from 32-112 percent was found in the 0-4 age group during those periods in which wastewater was used for irrigation as compared to the non-wastewater irrigation periods, regardless of the direction of the switch. Excess risk was not seen in other age groups. A small but significant excess risk of about 10 percent in effluent irrigating years was also found on an annual basis in each age group, as estimated by the log linear model only. None of the findings provided direct support for the hypothesis that the main pathway of pathogens transmission was aerosolized effluent resulting from sprinkler irrigation. Data from 68 kibbutzim, which were based on kibbutz clinic files, were compared with cases of salmonellosis, shigellosis and hepatitis reported to the Ministry of Health, and no serious ------- discrepancy was found between the two sources. A small, significant excess risk of total enteric disease was found during effluent irrigation periods but the present study did not confirm the extreme differences reported in a previous study of effluent irrigating kibbutzim. This Project Summary was developed by EPA's Health Effects Research Laboratory. Research Triangle Park, NC, to announce key findings of the research project that is fully documented in a separate report of the same title (see Project Report ordering information at back). Introduction Land application of wastewater serves both as an effective water pollution control measure and as a means of conserving water through recycling in areas suffering from shortages of water resources. In the United States, the U.S. Environ- mental Protection Agency (EPA) has been assigned the task of evaluating the technological feasibility and potential health effects of land application of wastewater as a major water pollution control strategy. In Israel, wastewater re- use in agriculture is part of the national water resources management policy in- tended to help close the gap between the limited amounts of renewable fresh water resources and the growing water demand associated with increasing populations. This policy has resulted in the establishment of some 250 wastewa- ter utilization projects, 90 percent of which practice sprinkler irrigation with oxidation pond effluent. By the year 2000, it has been estimated that Israel will be utilizing some 300-400 million cubic meters of effluent per year, primarily for agricultural purposes. The goal is that 80 percent of all municipal wastewater will be recycled in this manner. The most prominent form of wastewa- ter reuse in agriculture is by sprinkler irrigation. This results in the aerosoliza- tion of 0.1-1 percent of the effluent applied to the land. In the United States, sprinkler irrigation is also one of the most feasible modes of land application of wastewater. There has been concern that the extensive use of sprinkler irrigation with effluent may present a potential health hazard for field workers and the popula- tion adjacent to the fields. Humans may be infected by aerosols containing patho- genic bacteria or viruses by inhalation of particles of 0.5-5.0 nm which can enter the respiratory system. The larger droplets, however, can be trapped in the upper respiratory system including the nose and larynx, and from there they may reach the digestive tract. Other modes of transport of pathogens from areas irrigated with wastewater are by direct contact with irrigation workers, contami- nated crops and fomites. In 1975 investigators reported that pathogenic bacteria may be transported in aerosols from sewage to humans. A later survey emphasized the potential risk to sewage workers of enteric diseases from occupational exposure. Earlier studies also showed that microorganisms were isolated from aerosols at a distance of 1200 m downwind from a sewage treatment plant. However, there is little evidence of the degree of health risk from aerosolized sewage. A recent review of health effect studies of wastewater aerosols is contained in the proceedings of the EPA Symposium on Wastewater Aerosols and Disease. The studies reviewed did not provide clear- cut evidence as to the health risks, if any, associated with wastewater treatment or reuse. The Environmental Health Laboratory of the Hebrew University-Hadassah Medical School has succeeded in isolating coliforms at a distance of 350m, salmonella at a distance of 60m and enteroviruses at 100m downwind from the wastewater irrigated field. One of the first retrospective epidemic- logical studies on the possible health risks associated with sprinkler irrigation of wastewater was carried out in Israel. In this study, the data suggested that in 77 kibbutzim (cooperative agricultural settle- ments) practicing mainly sprinkler irriga- tion with undisinfected oxidation pond effluent, the incidence of typhoid fever, salmonellosis, shigellosis and infectious hepatitis was two to four times higher than in 130 control kibbutzim not practicing any form of effluent irrigation. Then investigators concluded that these findings "provide some epidemiological evidence for increased risk of enteric communicable diseases" among users of partially treated, non-disinfected wastewater for irrigation. The researchers themselves pointed out that from this study they could not provide definite proof that the suggested added health risk in effluent-utilizing kibbutzim was associated with the dispersion of pathogenic microorganisms by aerosols. This conclusion was drawn because a number of pathways of infection other than aerosols existed, such as direct personal contact via clothing or skin, of sewage irrigation and fish pond workers, or exposure to the crops, and fish grown in ponds using effluent. This preliminary survey also had serious methodological constraints in that investigators based their findings solely on official communicable disease reports which were submitted to the Ministry of Health as required by law. These require- ments do not include the listing of all relevant diseases, indicating serious reporting deficiencies. The comprehen- siveness of kibbutz reporting to the Ministry of Health is not known. Other methodological deficiencies existed also. For example, the irrigation period, as defined in that study, was arbitrarily set as April to November, rather than the actual irrigation period which varies from 3 to 12 months per year. The effluent irrigation status of the kibbutzim were determined according to the Ministry of Agriculture report of 1975 and assumed that the status was correct for the entire study period, while the disease data covered a period of from 2 to 13 years. In a check of the Ministry of Agriculture reports for available years 1971, 1975 and 1978, it was found, for example, that in the above-mentioned seven-year reporting period, there was an increase of about 35 percent in the number of kubbutzim irrigating with wastewater, while about 10 percent of the kibbutzim ceased wastewater irrigation. Thus about 45 percent of kibbutzum changed their wastewater irrigation status during the study period. Detailed data on the changes in category during the 13 years of the study are not available, but it can be assumed from the available data that a similar trend of changes in status may have occurred. In addition, a field check on the accuracy of the Ministry of Agriculture reports on wastewater irrigation status indicated that some 16 percent were incorrectly categorized. Moreover, in that study, communicable disease data for different diseases were based on varying periods of time—from two years for influenza, up to 13 years for typhoid fever—leading to difficulties in interpre- ting the epidemiological implications due to such factors as disease cycles and epidemic periods. For the above reasons, conclusive findings should not be based on that study. The World Bank monograph on appro- priate technology for water supply and sanitation states that the "Data on the health effects of night soil or sewage ------- upon sanitation or agricultural workers are inconclusive, although the risk is self- evident." This statement illustrates the ambiguous situation that exists in this area and which may lead to overly restrictive policies concerning wastewa- ter reuse - especially in those areas suffering from water shortages. What are required are carefully designed studies that can provide accurate data to assess the real nature of the risks involved in sewage reuse and can serve as a basis for developing a sound public health policy. In light of all the above problems, new research based on primary medical and environmental data collected at each kibbutz was carried out by this project to confirm or rebut the findings of the initial retrospective study of wastewater irriga- tion in kibbutzim. The full report covers a study of the health records during the years 1974-77. These were taken directly from the clinic files of 32,672 persons in 79 kibbutzim in the following categories: I. Thirty practicing sprinkler irriga- tion with wastewater and exposed to wastewater aerosols. II. Twenty-eight not exposed to waste- water aerosols, nor practicing any form of wastewater irrigation or utilization. This category served as the control group for categories I and III. III. Ten not exposed to wastewater aerosols by utilizing wastewater as feed water for fish ponds. IV. Eleven that switched from non- wastewater use to wastewater use or vice versa, thus serving as controls for themselves. In most cases, the method of wastewa- ter treatment prior to utilization was oxidation ponds, with 5-10 day detention periods. Coliform concentrations in efflu- ent were very high and usually ranged from 106~7/100 ml while enteric virus concentrations in effluent ranged from 102-103 PFU/100 ml. High concentra- tions of Salmonella organisms are commonly detected in municipal waste- water in Israel. These concentrations of enteric microorganisms were consider- ably higher than those at comparable land application sites in the United States. Thus, this project in Israel represents what may be considered a "worst case" of population exposure to wastewater land application practice in general, and aerosolized pathogens of sewage origin in particular. If little or no health risks can be detected under such extreme condi- tions of environmental exposure to pathogens, the risk associated with land application projects using significantly higher quality effluent may be negligible or nonexistent. If, however, some health risks are detected under the extreme conditions of this study, it will provide some indication of the type and degree of additional prophylactic measures which should be introduced to prevent or reduce the risks to an acceptable level. Conclusions 1. Based on simplified analyses, no excess of total enteric disease was observed in effluent irrigating (category I) kibbutzim (collective agricultural settle- ments) over non-effluent utilizing kibbut- zim (category II) during the irrigation period or on an annual basis. An excess of total enteric disease rates was observed in kibbutzim utilizing effluent as feed water for fish ponds (category III) over both categories I and II during the irrigation period and on an annual basis. Due to the numerous and complex confounding factors not controlled for in a simple comparison of crude rates, no attempt at drawing conclusions from these observations was made. It was concluded that a regression type analysis by the logistic and log linear models was required to control for con- founding factors in order to estimate the risk of enteric disease, if any, associated with the various wastewater utilization practices in the kibbutzim included in this study. 2. Not all distributional assumptions which underlie both the logistic and log linear models could be examined by the data. Those that were examined were found to be reasonably satisfied. The log linear model succeeded in explaining about 50 percent of the mtra- and inter-kibbutz variation of the enteric disease rates (R2 = .50) based on episodes culled from kibbutz clinic files. However, much of this apparently good fit is due to an artifact associated with the high correlation between enteric and control diseases, which might reflect differences in quality of reporting in the kibbutzim. Thus the fit, due to the mam variables under study, is considerably less. The fit for the logistic model was about the same as that of the log linear, after considering the effect of the quality of the reporting. The above conclusions concerning the basic assumptions and fit of the two models apply to the analysis of the risk of enteric disease for the 68 kibbutzim in which a comparison was made between 30 effluent irrigation kibbutzim (category I) as against the 28 control kibbutzim, in which only non-effluent was used for irrigation (category II) and the 10 kibbutzim using effluent as feed water for fish ponds (category III). The two models showed a far better fit for the data in the switch category (IV) design (11 kibbutzim that irrigated two years with non-effluent and switched to two years of effluent irrigation or vice versa). The coefficient of determination for the fit of the log linear model was very high (R2 = .94), with an equivalently good fit for the logistic model. It was concluded that, despite the numerous co-vanates entered into both models for the analysis of effluent vs. non- effluent utilization categories (the 68 kibbutzim), insufficient control of inter- kibbutz variations was obtained. On the other hand, these very same kibbutz- specific confounding factors were almost completely controlled for in the switch category. This was due to its block-type design with each community serving as its own control. Thus, the switch category provided a far superior design on which the conclusions of this study are mainly based 3. Both the logistic and log linear models used to estimate the risk of becoming ill with any of the 12 enteric diseases (total enteric) in association with various wastewater utilization practices in the study of the 68 kibbutzim in categories l-lll produced results which were often highly conflicting and full of anomalies, to the extent that is was not possible to draw clear and significant conclusions from most portions of the analysis of the data set. However, on an annual basis it could not be concluded from the study of the 68 kibbutzim that there was evidence of an excess risk of enteric disease in effluent irrigating kibbutzim (category I) over non-effluent irrigating kibbutzim (category II). The results did suggest that there might be an excess risk of enteric disease in effluent irrigating kibbutzim (category I) over non-effluent irrigating kibbutzim (category II) during the "period of exposure" to effluent (i.e., the actual months of irrigation as recorded for each individual kibbutz) with a deficit during the non-irrigation period, and no excess risk at all on an annual basis. There was also evidence pointing to an excess risk of enteric disease in both seasons and on an annual basis in kibbutzim utilizing effluent as feed water for fish ponds (category III) over category II. Caution should be used in evaluating these possible trends, particularly in relation to fish ponds, since this study did ------- not include a control group of non- effluent utilizing fish ponds. 4. Within category I, no correlation was found between crude enteric disease rates and the aerosol exposure index used, which included the following parameters: distance; wind direction and velocity; size of effluent irrigated field; and length of irrigation period. 5. The results of the study for the 68 kibbutzim, based on crude rates of specific diseases (shigellosis, salmonel- losis and infectious hepatitis) culled from both the kibbutz clinic files and from the Ministry of Health records of reported cases of communicable disease, did not confirm the findings of a previous study, which indicated an excess of 2.0-4.3 times for the above specific enteric diseases in effluent irrigating vs. non- effluent irrigating kibbutzim. Based on kibbutz clinic files, the shigellosis rates were found to be about 26 percent greater in effluent irrigation kibbutzim during the irrigation season as compared to non-effluent irrigating kibbutzim, but no excess for salmonellosis or infectious hepatitis was found, nor was there any excess risk of total enteric disease on an annual basis. 6. In the switch category (IV), the analysis by both the logistic and log linear models showed a significant increase in risk of enteric disease in the irrigation period during the effluent irrigating years over the non-effluent irrigating years for the 0-4 age group, regardless of whether the switch was from non-effluent to effluent or vice versa. The estimated excess in enteric disease ranged from 70 percent to 112 percent by the odds ratio (O.R.) as estimated by the logistic model and was about 30 percent according to the relative risk (R.R.) as estimated by the log linear model. There was also a significant excess risk of enteric disease in the other age groups during effluent irrigation periods, how- ever, without the same degree of uniform- ity as found in 0-4. The estimated excess ranged from 7-25 percent by O.R. and R.R. On an annual basis there was a signifi- cant excess risk of about 10 percent in eachage group separately and all ages by the log linear model, which was not found in the analysis by the logistic model. The findings by the logistic model analysis do not necessarily negate those of the log linear model. Thus, it was concluded that a small but significant excess risk of enteric disease on an annual basis did exist during the effluent irrigation years in the switch category. The finding of a significant excess risk of enteric disease in the irrigation season during the effluent irrigation years before the switch to non-effluent irrigation supports the suggestion that the risk associated with exposure to effluent is long term and not only associated with the introduction of wastewater irrigation into a previously unexposed community. 7. The findings in the switch category of an excess risk of enteric disease during the effluent irrigation months, but with little or no excess on an annual basis, can be explained, in part, by the results of the analysis of the annual cycles of crude enteric disease rates in the study of the 68 kibbutzim. The monthly crude rates for effluent irrigating kibbutzim (category I) were observed to increase rapidly shortly after initiation of irrigation. Monthly enteric disease rates for May-July were higher in I compared to II, dropping to a lower level for most of the remaining months of the year. This held for the 0-4 and the all ages groups. The annual crude rate of enteric disease in both I and II were the same. The control diseases showed the known inverse cyclical pattern peaking in December and January, with lows during the summer months. No differences in the annual cycle for control diseases between I and II were observed. The annual cycle of enteric disease suggests that, in category I, there may indeed be increased transmission of enteric disease on the initiation of wastewater irrigation in the spring, but that, in the unique kibbutz situation with intimate communal living including a common dining hall, there are continuous multiple exposures to enteric pathogens, which result in a certain annual satura- tion level of enteric disease, regardless of wastewater utilization practices. The annual appearance of lower enteric disease rates late in the irrigation period and after it, during the winter in category I as compared with category II, suggests that some form of short-term immunity may have developed in a portion of the exposed population. 8. Despite the evidence that there was an excess risk of total enteric disease in kibbutzim during the period of exposure to effluent (i.e., the effluent irrigation period), the annual excess risk for all ages was nil or quite small, thus indicating that the overall risk of enteric disease resulting from effluent irrigation in kibbutzim in Israel is not a public health problem in general, but might become one during epidemic periods. Many of these findings are related to the unique kibbutz lifestyle. Whether or not a similar degree of exposure of typical U.S. families in private homes in a non-communal situation, to enteric disease pathogens associated with wastewater effluent irrigation of similar quality would result in an excess risk of enteric disease on a seasonal or an annual basis cannot be determined from this study. 9. Extrapolation of these findings to situations of wastewater utilization in agriculture and/or land application in the United States must take into considera- tion the fact that, in general, the effluent used for irrigation at kibbutzim in Israel was only minimally treated in oxidation ponds with detention periods of 5-10 days. It was generally of poor microbial quality, having coliform concentrations of about 106/100 ml and enteric virus concentrations ranging from 102-103 PFU/ 100 ml. Whether or not the same degree of risk of enteric disease associ- ated with wastewater utilization found in this study would exist if better treated ef- fluents, typical of those from convention- al biological treatment plants or their equivalent, had been used was not eval- uated. 10. Caution must be used in the interpretation and application of all of the above conclusions in light of the many methodological problems associated with this retrospective study. Recommendations 1. In light of the finding that a significant risk of enteric disease during irrigation periods was associated with irrigation with effluent from short detention period oxidation ponds having low efficiency in the removal of enteric microorganisms in kibbutzim in Israel, it is recommended that a higher degree of effluent treatment be provided as a prudent public health measure. Even though the excess risk on an annual basis is nil or small, the higher level of treatment can be justified as a safety factor particularly to reduce possible increased disease transmission during epidemic periods. 2. Despite the numerous methodologi- cal problems revealed in estimating the risk of enteric disease associated with the use of similar quality effluent as feed water in fish ponds, the evidence points to the presence of an excess risk in this group of kibbutzim in Israel, which justifies taking precautionary measures. It is recommended that a higher level of treatment, assuring more efficient re- moval of enteric microorganisms, be provided prior to discharge of effluent to fish ponds or that effluent use be avoided. 4 ------- 3. In Israel and other countries suffer- ing from serious water shortages, where effluent reuse and/or land application has become a matter of national water planning policy, society should provide long-term health monitoring programs to achieve an unambiguous evaluation of the risk to the public and to determine the type of preventative action required where significant excess risk is revealed. This applies in particular to areas where previously unexposed populations will be involved in effluent irrigation and/or land application programs for the first time. 4. Due to the serious methodological problems revealed in this retrospective study, it is recommended that the pro- spective investigations be conducted to gather more conclusive data concerning potential health risks associated with land application of wastewater. 5. It is recommended that special emphasis be given to improving the comprehensiveness and consistency of medical recording and that all sources be utilized, including the nurses' and doctors' daily logs. Investigation of outbreaks and special studies on the highly susceptible groups of volunteers should be included. Of critical importance is the sampling of blood and stools in children, effluent workers and volunteers so as to determine infectivity rates and immunity in relation to effluent exposure. These cannot be readily detected by recording cases of clinical disease. 6. Further research should study the apparent association between effluent utilization and the excess of control diseases such as streptococcal throat infections observed in this study. This study was carried out at the Environmental Health Laboratory of the School of Public Health and Community Medicine, Hebrew University - Hadassah Medical School, Jerusalem, Israel under U.S. Environmental Protection Agency Grant No. R-805174. The study was initiated in October 1977 and completed March 1, 1982. Project Officer Comment - The main reason for support of this research was to follow up on the report in Science, 194 (1976) that there was a marked health hazard from wastewater spray irrigation. The authors could not confirm that earlier finding, and, in fact, discovered serious deficiencies in the data used in that study. They also imply that the data base provided by the kibbutzim is inadequate for a conclusive study and that caution should be exercised in interpreting the report due to the study's many methodo- logical problems. Neither the numerator nor denominator could be reliably deter- mined to calculate illness rates and ratios. A complex statistical analysis was necessary as an attempt to control for the inadequacies of the data as well as to adjust for differenes in influential factors. A clear understanding of the methods used for data analysis is necessary in order to interpret the results and evaluate the findings of the study. H. I. Shuval. B. Fattal, and Y. Wax are with the Hebrew University—Hadassah Medical School, Jerusalem, Israel 9 WOO. Walter Jakubowski is the EPA Project Officer (see below). The complete report, entitled "Retrospective Epidemiological Study of Disease Associated with Wastewater Utilization." (Order No. PB 84-190 727; Cost: $14.50, subject to change) will be available only from: National Technical Information Service 5285 Port Royal Road Springfield, VA22161 Telephone: 703-487-4650 The EPA Project Officer can be contacted at: Health Effects Research Laboratory U.S. Environmental Protection Agency Research Triangle Park, NC 27711 . S. 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