Sporadic Cryptosporidiosis decline after membrane filtration of public water supplies, England, 1996-2002.

The incidence of sporadic cryptosporidiosis among 106,000 residents of 2 local government districts in northwest England before and after installation of membrane filtration of public water supplies was compared to that of 59,700 residents whose public water supplies remained unchanged. A national outbreak of foot and mouth disease in livestock during 2001 was associated with a decline in sporadic human cryptosporidiosis in all regions of the United Kingdom. In a Poisson regression model, membrane filtration was associated with an estimated 79% reduction (incidence ratio 0.207, 95% confidence intervals 0.099-0.431, p < 0.0001) after adjustment for the interval of the foot and mouth disease epidemic and the water source. Despite the confounding effect of that epidemic, membrane filtration of the public water supply was effective in reducing the risk for sporadic human Cryptosporidium infection in this population.

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Cryptosporidium is a genus of enteric parasites that cause diarrhea in humans and many animal species worldwide; it is the third most common cause of nonviral infectious diarrhea reported in England and Wales (1,2). Oocysts are shed in large numbers in feces of infected humans and animals and contain highly infectious sporozoites when ingested (1,3). Disease may be prolonged and fatal in immunocompromised persons (1). Cryptosporidium hominis (previously designated C. parvum genotype 1) is found in humans but occurs naturally in livestock animals very rarely; C. parvum (previously designated C. parvum genotype 2) infects humans and livestock (4-6).

Cryptosporidium oocysts are a threat to the safety of drinking water supplies because they remain viable in water and damp soils for prolonged periods and are resistant to concentrations of disinfectants, including chlorine, used in conventional water treatment. Removal of these oocysts depends on sedimentation, coagulation, and filtration (1,7,8). We have previously reported a prospective case-control study of risk factors for sporadic cryptosporidiosis in residents of Allerdale and Copeland local government districts in North Cumbria, rural northwest England, from March 1, 1996, to February 29, 2000. That study showed a strong association with the usual daily volume of cold unboiled tap water drunk and with short visits to farms (9). We present extended observation of the population to August 31, 2002, during which time membrane filtration of public drinking water supplies was introduced for two thirds of the study population and a national outbreak of foot and mouth disease (FMD) in livestock occurred.

Materials and Methods

The study area comprises part of the Lake District National Park. The lakes act as natural reservoirs for local public water supplies and have livestock farms and open grazing land abutting them. Approximately one third of the study population receive public water supplies from Ennerdale Lake, one third from Crummock Lake, and one third from a number of smaller sources. From March 1, 1996, to February 29, 2000, water from Ennerdale and Crummock Lakes was disinfected with chlorine, but unfiltered, because the low level of particulate matter in these sources precluded chemically assisted flocculation. Membrane filtration began on March 1, 2000, at works treating water from Ennerdale and Crummock Lakes and remained active until the end of the study. The remaining third of the population received water from a number of smaller sources undergoing a variety of conventional treatments, including coagulation, filtration and chlorination, and chlorination alone. No changes in the treatment of water from these other sources occurred at any time.

FMD Epidemic in Livestock

The first FMD case in livestock was confirmed on February 21, 2001, in southeast England and the last case on September 30, 2001, in northwest England (10). Epidemic controls were enforced throughout the United Kingdom; they included culling livestock, excluding livestock from traditional pastures, limiting livestock movements, and excluding the public from the countryside. The FMD epidemic was associated with marked attenuation of the usual spring peak in human cryptosporidiosis reporting from all regions of England and Wales and with a decline predominantly of C. parvum (livestock and human species). FMD epidemic controls were applied uniformly across the Allerdale and Copeland Districts and ended on January 21, 2002.

Analysis of risk factors and laboratory' testing for Cryptosporidium were undertaken as previously described; cases with date of onset from March 1, 2000, to August 31, 2002, and associated controls were added (5,9). To determine if introduction of membrane filtration and the FMD epidemic in livestock were associated with a change in risk factors or incidence of human cryptosporidiosis, observations were divided into 5 intervals: before commissioning of membrane filtration (March 1, 1996, to February 29, 2000); membrane filtration commissioning (March 1, 2000, to July 31, 2000); established membrane filtration before the FMD epidemic (August 1, 2000, to February 20, 2001); the FMD livestock epidemic to ending of local FMD epidemic controls (February 21, 2001 to January 20, 2002); and post-FMD epidemic (January 21, 2002, to August 31, 2002).

Case Definition

Case-patients were residents of Allerdale or Copeland who had diarrhea ([greater than or equal to] 3 loose stools in a 24-hour period) with onset from March 1, 1996, to August 31, 2002; were fecal smear positive for Cryptosporidium oocysts, but feces negative for other enteric pathogens; and had spent at least 1 night within the study area in the 14 days before onset. Patients were excluded if, within 14 days of onset, they had contact with another household patient with cryptosporidiosis or any diarrhea illness, traveled outside the United Kingdom, or traveled within the United Kingdom and stayed outside the study area during the entire 14-day period before onset of illness; or if they, or a household member, had already been enrolled as a case-patient or control at any time during the study.

Control Definition

Controls were residents of Allerdale or Copeland who had no history of diarrhea (defined as [greater than or equal to] 3 loose stools in a 24-hour period) and had spent at least 1 night within the study area in the 14 days before interview. Potential controls were excluded if they had traveled outside the United Kingdom in the 14 days before the date of interview or if they had traveled within the United Kingdom and stayed outside the study area during the entire 14 day period before the date of interview. Potential controls were also excluded if they or a household member had already been enrolled as a case-patient or control at any time during the study.

The local water company provided details of the water sources, water supply zones, number of houses and residents served by each water source and water supply zone, and treatment of water to each zone. The study team and water company maintained vigilance for changes in the water supplies to the population at all stages of the study. In a minority of participants, the water source changed; these case-patients and controls were categorized as receiving mixed supplies from >1 source.

Risk Factor Analysis

Five sets of contingency tables, 1 for each interval of observation defined by introduction of membrane filtration and the FMD epidemic, were constructed for each exposure variable, and odds ratios were calculated. Main effects variables were defined as those significant at p < 0.2 in any of the 5 sets of contingency tables. These variables--interval, age, sex, and water supply zone--were put into a multivariable model. Stepwise sequential removal of variables with p > 0.05 was undertaken retaining time interval, age, sex, and water supply zone. The significance of interaction terms between time interval and the remaining main effects variables was tested in separate models with stepwise sequential removal of terms with p > 0.05.

Incidence Rates and Incident Rate Modeling

Incidence rates were determined for residents by water supply zone and modeled by Poisson regression using the number of cases as the predictor variable and the number of person-years of observation as the offset (11,12). The models had 3 predictor variables: membrane filtration (before and after), FMD epidemic (before, during, and after local FMD controls), and water source (Ennerdale, Crummock, and "other" water supplies). The interaction between these predictors was explored. The models provided estimates of the incidence rate ratio (IRR). The goodness-of-fit of the models was assessed. The species of Cryptosporidium isolates before and after membrane filtration were compared.

Results

Population and Water Supplies

Public water supplies derived from Crummock Lake served 58,295 residents; from Ennerdale Lake, 47,780 residents; and from a variety of other smaller water sources, including a few private water supplies, the remaining 59,699 residents of Allerdale and Copeland (Appendix Table 1; available from http://www.cdc.gov/ncidod/EID/ vol11no2/04-0274_app.htm). Public drinking water supplies derived from Crummock and Ennerdale Lakes before March 1, 2000, were chlorinated but not filtered (Appendix Table 1). Separate membrane filtration plants at water treatment works at Crummock and Ennerdale Lakes were commissioned from March 1, 2000, to July 31, 2000; full operation was achieved by August 1, 2000. These plants remained fully operational until the end of the study, August 31, 2002. The treatment of water derived from other sources remained unchanged for the study period. These multiple smaller sources received a variety of conventional treatments, including coagulation, filtration and chlorination, and chlorination alone. In addition, a small number of houses had private water supplies, which were untreated (Appendix Table 1).

Recruitment and Exclusion of Patients

A total of 249 patients identified as having sporadic cryptosporidiosis were ascertained during the study period; 74 (30%) were excluded, and 175 (70%) were enrolled (Table 1). Of the 175 primary cases of cryptosporidiosis enrolled, 153 (87%) had onset dates from March 1, 1996, to February 29, 2000, before the commissioning of membrane filtration at Crummock and Ennerdale Lakes; 22 (13%) patients had onset from March 1, 2000, to August 31, 2002, after the membrane filtration plants were introduced (Table 1).

Recruitment and Exclusion of Controls

A total of 929 potential controls were approached during the study; 392 (42%) were excluded, and 537 (58%) were enrolled. Two hundred and twenty one (24%) persons either refused to participate or were repeatedly unavailable for interview (Table 1). The address was not found for 3 (<1%). One hundred twelve (12%) were excluded because they did not meet the study control definition for a variety of reasons (Table 1). Fifty-six (6%) were not enrolled for administrative reasons. The study team cancelled interviews for 44 (5%) because 3 control interviews had been completed for the associated case and 9 (1%) interviews because the potential controls were found to be in the wrong age band; the reason for exclusion was not recorded for 3 potential controls (<1%). Of the 537 controls enrolled, 468 (87%) had interview dates from March 1, 1996, to February 29, 2000; and 69 (12.9%) had interviews from March 1, 2000, to August 31, 2002 (Table 1).

Study Population

Patients

Of the 175 case-patients, 150 (86%) were <16 years of age, and 96 (55%) were <6 years of age. Ninety (51%) were male (Table 2). The proportion of cases <16 years of age and the proportion who were male were lower after membrane filtration was introduced into Crummock and Ennerdale Lake water. The proportion of case-patients served by water from other sources that never received membrane filtration was higher after introduction of membrane filtration (Table 2).

In addition to diarrhea, a substantial proportion of patients had abdominal pain, vomiting, fever, loss of appetite, and weight loss (Appendix Table 2). Forty-two (24%) patients remained symptomatic at interview. Of the 133 (76%) whose symptoms had abated at interview, the median duration of illness was 9 days (range 2-21 days) (Appendix Table 2). In children <6 years of age, 14 (25%) of 55 of boys and 6 (15%) of 41 girls were admitted to hospital because of diarrhea (Appendix Table 3). The admission rates in children 6-15 years of age were 3 (11%) of 28 boys and 3 (12%) of 26 girls. Most of the patients and all male patients <6 years of age had onset dates before the membrane filtration was introduced (Appendix Table 3). Twenty-six (17%) of the 150 patients who were <16 years of age were admitted to hospital, but none over this age.

Species identification was undertaken for 68 fecal specimens from patients with onset from January 1, 1998, to February 29, 2000 (Appendix Table 4). Fifty-seven (84%) were C. parvum. Thirteen (81%) of the 16 smears derived from patients with onset dates from March 1, 2000, to August 31, 2002, were also C. parvum. Overall, 70 (83.3%) of the 84 specimens for which the species was identified were C. parvum.

Controls

The 537 controls had similar age, sex, and drinking water supplies as the 175 patients (Table 2). The time between notification of a case by a microbiology laboratory to the study-coordinating center to enrollment of the patient and his or her associated controls was a median of 2 weeks (range 1-8 weeks) and was similar before and after the introduction of membrane filtration.

Risk Factor Analysis

None of the interaction terms between the main effects variables and time intervals of observation, defined by introduction of membrane filtration and the FMD epidemic in livestock, were significant, including the term for the usual volume of cold unboiled tap water drunk per day (p = 0.12). These interaction terms were therefore excluded from the final multivariable risk factor model (Table 3). The risk for sporadic cryptosporidiosis was independently associated with the usual volume of cold unboiled tap water drunk each day, with contact with cattle farms and noncattle farms, and with feeding pets leftovers. Water supply zones, the time interval of observation, age, and gender were not independently associated with having a case (Table 3).

Incidence and Seasonality

The incidence within the populations served by public water supplies derived from Ennerdale Lake, Crummock Lake, and other water sources was similar before March 2000 at [approximately equal to] 22 cases per 100,000 person years but declined to <10 per 100,000 person years after March 1, 2000 (Table 4) (Figure 1). The decline was more marked in the populations served by water derived from treatment works at Ennerdale and Crummock Lakes, where membrane filtration plants had been installed, than in the population served by other water sources, where membrane filtration was not installed. A well-defined spring peak in cases was apparent from 1996 to 1999, but not from 2000 to 2002 (Figures 2 and 3).

[FIGURES 1-3 OMITTED]

After membrane filtration was introduced for Crummock and Ennerdale supplies, an estimated reduction in incidence of [approximately equal to] 79% occurred (IRR 0.207, 95% confidence intervals [CI] 0.099-0.431), p < 0.0001, after adjustment for the FMD epidemic interval and water source in a Poisson regression model (Table 5). The decrease attributed to the FMD interval was [approximately equal to] 60% (IRR 0.394, 95% CI 0.167-0.925), with some evidence of a residual effect after the end of local FMD epidemic controls (IRR 0.686, 95% CI 0.292-1.61). No additional effect was contributed by water source (p = 0.6). The data for this model are presented graphically in Figure 1 and detailed in Table 4. Little difference was made by modeling the intervals for commissioning and postcommissioning of membrane filtration separately, and no significant difference was seen between these rate estimates when this modeling was done (p = 0.35)

Discussion

Consumption of cold unboiled tap water from public drinking water supplies was shown to be a leading independent risk factor for sporadic cryptosporidiosis with a highly significant increase in risk with the usual volume drunk each day (Table 3). Risk was also increased by contact with cattle farms and noncattle farms and with feeding pets leftovers. Fifty five percent of patients were <6 years of age, and 31% were 6-15 years. Infection was predominantly with C. parvum (livestock and human species). The results of the risk factor analysis for the entire study period were similar to those obtained for the interval before installation of membrane filtration, when most cases arose (9). Illness was prolonged and almost one fifth of children <6 years of age required hospital admission. The excess in hospitalization in boys <6 years of age may suggest that young boys are more vulnerable to Cryptosporidium than young girls, a bias in favor of admitting young boys, or a combination of these factors.

The 2001 FMD epidemic in livestock, which occurred after membrane filtration was introduced in Allerdale and Crummock Lake water, affected all regions of the United Kingdom (10). This livestock epidemic was associated with a highly significant decline in laboratory reports of human cryptosporidiosis from all regions of England and Wales and was more marked in Northwest England. The decline in reports was most marked for C. parvum (the species infectious in humans and livestock species) than for C. hominis (infectious only in humans) (10). The FMD epidemic control measures of excluding the public from the countryside, extensively culling farm animals, and limiting animal movements probably decreased direct and indirect exposure of the human population to livestock and livestock feces.

The annual agricultural and horticultural census conducted by the U.K. Department for Environment, Food and Rural Affairs and its predecessor, the Ministry of Agriculture, Food and Fisheries showed >600,000 sheep, 300,000 lambs, 100,000 total cattle and calves, and 40,000 calves <1 year of age in each of the years 1996-2000 within the 135,000 hectares of agricultural land in Allerdale and Copeland local government districts (13,14). A substantial decline occurred in 2001 and 2002 associated with the FMD epidemic, but no evidence suggested that the decline in animal densities or change in human contact with livestock and with the countryside differed within Allerdale and Copeland, according to the sources or distribution of the public drinking water supplies (13,14). The decline in incidence attributable to the FMD epidemic effect was therefore expected for our entire study population, regardless of its household water supply. We therefore believe that the experience of the population served by other supplies provided a valid measure of the impact of the FMD epidemic in livestock, whereas the population served by water from Ennerdale and Crummock Lakes experienced the effect of both membrane filtration and the FMD epidemic. The results of the Poisson regression model indicated a marked reduction of incidence in sporadic cryptosporidiosis following introduction of membrane filtration after adjustment for the FMD epidemic interval and water source (Table 5). Despite the confounding effect of the FMD epidemic, our study provides convincing evidence that membrane filtration was highly effective in reducing the risk for sporadic cryptosporidiosis in this population; this measure was also associated with a decline in hospital admissions for cryptosporidiosis in children, especially of boys <6 years of age.

The incidence rates associated with other supplies from a number of different sources and treatment works, some using conventional flocculation and filtration, were similar from March 1996 to February 2001 to the rates in the population served by Crummock and Ennerdale Lakes, whose water was unfiltered at this time. This finding supports the notion that conventional sand filtration and flocculation may be insufficient to prevent intermittent low-level Cryptosporidium oocyst contamination of treated water. The local water company has since closed higher risk sources and substituted them with water from lower risk catchments.

Our observations strongly support recent revision of the UK drinking water regulations requiring water companies to undertake risk assessments of water sources, and where judged to be a risk, to implement continuous monitoring of Cryptosporidium oocyst concentrations in treated water (15). A minimum standard of an average of <1 oocyst per 10 L of water in any 24-hour period is required.

The substantial negative impact of waterborne cryptosporidiosis leading to potentially life-threatening diarrhea and stunting in childhood is well-recognized in developing countries (16,17). Our findings show that Cryptosporidium remains an obstacle in water and sanitation infrastructure and a threat to child health in industrialized countries as well. The scale of this effect will continue to be underestimated if adequate surveillance of cryptosporidiosis by testing diarrheal feces specimens for Cryptosporidium and collation of positive test results, especially in children, is omitted by health services (18). Although the study population was located in an area of livestock farming with high historic rates of cryptosporidiosis in England, the demonstration that public drinking water supplies were a leading independent risk factor for sporadic cryptosporidiosis and that introduction of membrane filtration at water treatment works was effective in substantially lowering this risk, may have relevance to water companies, regulators, policymakers, and consumers in other countries.

Table 1. Exclusions and recruitment and controls

                                                  n (%)

                                    Before membrane    After membrane
                                      filtration,        filtration,
                                    March 1, 1996-     March 1, 2000-
Exclusion criteria                 February 29, 2000   August 31, 2002

Case-patients
Refused to participate                  1 (0.5)             0 (0)
Could not complete adequate             1 (0.5)            1 (2.4)
interview
Did not respond to letters or           2 (1.0)             0 (0)
phone calls
Did not meet study case
definition
  No history of diarrhea                1 (0.5)            1 (2.4)
  Mixed enteric infection               1 (0.5)               0
  Secondary case                       36 (17.4)          10 (23.8)
  Travel outside UK in 14 days          8 (3.9)           8 (19.0)
  before onset
  Visitor to study area                 1 (0.5)             0 (0)
  Residence outside study area          1 (0.5)             0 (0)
  Case-patient or household             2 (1.0)             0 (0)
  member previously interviewed
  as case or control
Potential case-patients                207 (100)          42 (100)
approached
Potential cases excluded               54 (26.1)          20 (47.6)
Total case-patients enrolled          153 (73.9)          22 (52.4)

Controls
Refused or unavailable for
interview
  Refused to participate               23 (3.0)           12 (7.9)
  Unavailable at requested            125 (17.1)          23 (15.2)
  interview times
  Said interview times were not        35 (4.5)            3 (2.0)
  convenient
Address not found                       3 (0.4)             0 (0)
Did not meet study control
definition
  History of diarrhea                  46 (5.9)            6 (4.0)
  Travel outside UK in 14 days          8 (1.0)            4 (2.6)
  before interview
  Not resident in study area in         3 (0.4)            1 (0.7)
  14 days before interview
  Moved from study area                27 (3.5)            7 (4.6)
  Residence outside study area          2 (0.3)             0 (0)
  Control or household member           7 (0.9)            1 (0.7)
  already interviewed as a
  case or control
Not enrolled for administrative
reasons or reason not recorded
  Interview cancelled; 3               19 (2.4)           25 (16.6)
  controls already enrolled
  for associated case
  Interview cancelled; potential        9 (1.2)             0 (0)
  control found to be in wrong
  age group
  Reason for exclusion not              3 (0.4)             0 (0)
  recorded
Potential controls approached          778 (100)          151 (100)
Potential controls excluded           310 (39.8)          82 (54.3)
Total controls enrolled               468 (60.2)          69 (45.7)

                                         n (%)

                                   Before and after
                                       membrane
                                      filtration,
                                    March 1, 1996-
Exclusion criteria                  August 31, 2002

Case-patients
Refused to participate                  1 (0.4)
Could not complete adequate             2 (0.8)
interview
Did not respond to letters or           2 (0.8)
phone calls
Did not meet study case
definition
  No history of diarrhea                2 (0.8)
  Mixed enteric infection               1 (0.4)
  Secondary case                       46 (18.5)
  Travel outside UK in 14 days         16 (6.4)
  before onset
  Visitor to study area                 1 (0.4)
  Residence outside study area          1 (0.4)
  Case-patient or household             2 (0.8)
  member previously interviewed
  as case or control
Potential case-patients                249 (100)
approached
Potential cases excluded               74 (29.7)
Total case-patients enrolled          175 (70.3)

Controls
Refused or unavailable for
interview
  Refused to participate               35 (3.8)
  Unavailable at requested            148 (15.9)
  interview times
  Said interview times were not        38 (4.1)
  convenient
Address not found                       3 (0.3)
Did not meet study control
definition
  History of diarrhea                  52 (5.6)
  Travel outside UK in 14 days         12 (1.3)
  before interview
  Not resident in study area in         4 (0.4)
  14 days before interview
  Moved from study area                34 (3.7)
  Residence outside study area          2 (0.2)
  Control or household member           8 (0.9)
  already interviewed as a
  case or control
Not enrolled for administrative
reasons or reason not recorded
  Interview cancelled; 3               44 (4.7)
  controls already enrolled
  for associated case
  Interview cancelled; potential        9 (1.0)
  control found to be in wrong
  age group
  Reason for exclusion not              3 (0.3)
  recorded
Potential controls approached          929 (100)
Potential controls excluded           392 (42.2)
Total controls enrolled               537 (57.8)

Table 2. Baseline characteristics and controls

                                                n (%)

                                  Before membrane    After membrane
                                    filtration,        filtration,
                                  March 1, 1996-     March 1, 2000-
Characteristics                  February 29, 2000   August 31, 2002

Case-patients, total                 153 (100)          22 (100)
Sex
  Female                             70 (45.8)          15 (68.2)
  Male                               83 (54.2)          7 (31.8)
Age
  <1-5                               87 (56.9)          9 (40.9)
  6-15                               47 (30.7)          7 (31.8)
  16+                                19 (12.4)          6 (27.3)
Water sources and water supply
  zones
  Crummock Lake
    Crummock North                   37 (24.2)           2 (9.1)
    Crummock South                   19 (12.4)          4 (18.2)
  Ennerdale Lake
    Ennerdale North                  30 (19.6)           2 (9.1)
    Ennerdale South                  13 (8.5)            1 (4.5)
  Other sources
    Millom                           19 (12.4)          3 (13.6)
    Quarry Hill                      16 (10.5)          6 (27.3)
    Hausegill                         3 (2.0)               0
    Hayknott                          2 (1.3)               0
    Underscar                         1 (0.7)            2 (9.1)
    Fellside                             0                  0
    Mixed >1 source                  11 (7.2)            1 (4.5)
    Different private water           2 (1.3)            1 (4.5)
      supplies

Controls, total                      468 (100)          69 (100)
Sex
  Female                             234 (50)           31 (44.9)
  Male                               234 (50)           38 (55.1)
Age
  <1-5                              273 (58.3)          27 (39.1)
  6-15                              137 (29.3)          20 (29.0)
  16+                                58 (12.4)          12 (17.4)
Water sources and water supply
  zones
  Crummock Lake
    Crummock North                  104 (22.2)          7 (10.1)
    Crummock South                   49 (10.5)          13 (18.8)
  Ennerdale Lake
    Ennerdale North                 100 (21.4)          7 (10.1)
    Ennerdale South                  43 (9.2)            3 (4.3)
  Other sources
    Millom                           54 (11.5)          10 (14.5)
    Quarry Hill                      42 (9.0)           16 (23.2)
    Hausegill                         5 (1.1)               0
    Hayknott                          6 (1.3)            1 (1.4)
    Underscar                         3 (0.6)            6 (8.7)
    Fellside                             0               2 (2.9)
    Mixed >1 source                   1 (0.2)               0
    Different private water          51 (10.9)           4 (5.8)
      supplies
  Crummock Lake                      10 (2.1)               0

                                       n (%)

                                    Before and
                                  after membrane
                                    filtration,
                                  March 1, 1996-
Characteristics                   August 31, 2002

Case-patients, total                 175 (100)
Sex
  Female                             85 (48.6)
  Male                               90 (51.4)
Age
  <1-5                               96 (54.9)
  6-15                               54 (30.9)
  16+                                25 (14.3)
Water sources and water supply
zones
  Crummock Lake
    Crummock North                   39 (22.3)
    Crummock South                   23 (13.1)
  Ennerdale Lake
    Ennerdale North                  32 (18.3)
    Ennerdale South                  14 (8.0)
  Other sources
    Millom                           22 (12.6)
    Quarry Hill                      22 (12.6)
    Hausegill                         3 (1.7)
    Hayknott                          2 (1.1)
    Underscar                         3 (1.7)
    Fellside                             0
    Mixed >1 source                  12 (6.9)
    Different private water           3 (1.7)
    supplies

Controls, total                      537 (100)
Sex
  Female                            265 (49.3)
  Male                              272 (50.7)
Age
  <1-5                              300 (55.9)
  6-15                              157 (29.2)
  16+                                70 (13.0)
Water sources and water supply
zones
  Crummock Lake
    Crummock North                  111 (20.7)
    Crummock South                   62 (11.5)
  Ennerdale Lake
    Ennerdale North                 107 (19.9)
    Ennerdale South                  46 (8.6)
  Other sources
    Millom                           64 (11.9)
    Quarry Hill                      58 (10.8)
    Hausegill                         5 (0.9)
    Hayknott                          7 (1.3)
    Underscar                         8 (1.5)
    Fellside                          2 (0.4)
    Mixed >1 source                   1 (0.2)
    Different private water          55 (10.2)
    supplies
  Crummock Lake                      10 (1.9)

* Mixed: mixed supply derived from Ennerdale and Crummock, or from
Ennerdale and another source, or from Crummock and another source.

Table 3. Final multivariable model of risk factors for sporadic
cryptosporidiosis, Allerdale and Copeland residents,
March 1, 1996, to August 31, 2002

                                                          Adjusted odds
Risk factors                 Case-patients    Controls       ratio *

Sex
  Female                          85            265             1
  Male                            90            272            0.73
Age
  <1-5                            96            300          1.002/y
  6-15                            54            157
  16+                             25             70
Water sources and water
  supply zones
  Crummock Lake
    Crummock North                39            111             1
    Crummock South                23             62           1.262
  Ennerdale Lake
    Ennerdale North               32            107            1.25
    Ennerdale South               14             46           0.556
  Other sources
    Millom                        22             64           1.502
    Quarry Hill                   22             58           0.703
    Hausegill                      3             5            1.356
    Hayknott                       2             7            1.016
    Underscar                      3             9            0.983
    Fellside                       0             1            0.005
    Bridgend                       0             2            0.004
  Mixed public supplies           12             55           0.893
  Private water supplies           3             10            0.10
Usual daily volume of cold                                    1.543
  unboiled tap water drunk                                  per pint
at home
  <1/4 pint                       25            122
  1/4-1 pint                      78            260
  >1-2 pints                      46            106
  >2 pints                        22             42
Contact with a cattle farm
  Yes                             19             29           4.532
  No                              144           475
Contact with a noncattle
farm
  Yes                             17             24           3.809
  No                              146           471
Feed pet leftovers
  Yes                             14             19           3.746
  No                              161           515
Interval of study
  March 1, 1996-                  153           468             1
    February 29, 2000
  March 1, 2000-                   4             16           0.965
    July 31, 2000
  August 1, 2000-                  6             16           1.115
    February 20, 2001
  February 21, 2001-               6             18           0.367
    January 21, 2002
  January 11, 2002-                6             19           0.485
    August 31, 2002

                             Lower 95% CI      Upper
Risk factors                  ([dagger])       95% CI        p value

Sex
  Female                         0.45          1.184          0.202
  Male
Age
  <1-5                           0.938         1.021          0.872
  6-15
  16+
Water sources and water                                       0.556
  supply zones
  Crummock Lake
    Crummock North
    Crummock South               0.547         2.913
  Ennerdale Lake
    Ennerdale North              0.594          2.63
    Ennerdale South              0.164         1.881
  Other sources
    Millom                       0.686         3.288
    Quarry Hill                  0.273          1.81
    Hausegill                    0.22           8.34
    Hayknott                      0.1          10.29
    Underscar                     0.1           9.18
    Fellside                       0         [infinity]
    Bridgend                       0         [infinity]
  Mixed public supplies          0.32          2.494
  Private water supplies         0.007           1
Usual daily volume of cold       1.212         1.965          <0.001
  unboiled tap water drunk
at home
  <1/4 pint
  1/4-1 pint
  >1-2 pints
  >2 pints
Contact with a cattle farm
  Yes                            1.757         11.69          0.002
  No
Contact with a noncattle
farm
  Yes                            1.677         8.651          0.002
  No
Feed pet leftovers
  Yes                            1.214         11.56          0.021
  No
Interval of study                                             0.585
  March 1, 1996-
    February 29, 2000
  March 1, 2000-                 0.235         3.958
    July 31, 2000
  August 1, 2000-                0.319         3.895
    February 20, 2001
  February 21, 2001-             0.078          1.72
    January 21, 2002
  January 11, 2002-              0.138         1.701
    August 31, 2002

* Adjusted for accidentally touching animal feces, feeding pets
biscuits, feeding pets raw vegetables, contact with anyone outside
the household with a history of diarrhea, type of sewage system to
the house, consumption of mixed salad, and local authority of
residence.

([dagger]) CI, confidence interval.

Table 4. Incidence of sporadic cryptosporidiosis by water source,
March 1, 1996-August 31, 2002

                                      Membrane
                                     filtration
Water source and time intervals *       (MF)        Cases (n)

Crummock Lake
  Before MF interval                     No             56
After MF interval
  Commissioning MF                      Yes             1
  Established MF pre-FMDE               Yes             1
  Established MF and FMDE               Yes             1
  Established MF and post-FMDE          Yes             3
  Total after MF                        Yes             6
Ennerdale Lake
  Before MF interval                     No             43
After MF interval
  Commissioning MF                      Yes             0
  Established MF pre-FMDE               Yes             1
  Established MF and FMDE               Yes             2
  Established MF and post-FMDE          Yes             0
Total after MF                          Yes             3
Other sources
  Before MF interval                     No             54
After MF interval
  Commissioning MF                       No             3
  Established MF pre-FMDE                No             4
  Established MF and FMDE                No             3
  Established MF and post-FMDE           No             3
  Total after MF                         No             13

                                                     Rate per
                                                     100,000
Water source and time intervals *   Person-years   person-years

Crummock Lake
  Before MF interval                  233,623         23.97
After MF interval
  Commissioning MF                     25,726          3.89
  Established MF pre-FMDE              33,970          2.94
  Established MF and FMDE              54,902          1.82
  Established MF and post-FMDE         31,490          9.53
  Total after MF                      146,088          4.11
Ennerdale Lake
  Before MF interval                  191,053         22.51
After MF interval
  Commissioning MF                     20,258           0
  Established MF pre-FMDE              27,223          3.67
  Established MF and FMDE              46,387          4.31
  Established MF and post-FMDE         26,606           0
Total after MF                        120,474          2.49
Other sources
  Before MF interval                  238,265         22.66
After MF interval
  Commissioning MF                     24,449         12.27
  Established MF pre-FMDE              32,257          12.4
  Established MF and FMDE              51,997          5.77
  Established MF and post-FMDE         29,824         10.06
  Total after MF                      138,527          9.38

Water source and time intervals *   95% CI ([dagger])

Crummock Lake
  Before MF interval                 (18.113, 31.13)
After MF interval
  Commissioning MF                    (0.10, 21.66)
  Established MF pre-FMDE             (0.07, 16.40)
  Established MF and FMDE             (0.05, 10.15)
  Established MF and post-FMDE        (1.96, 27.84)
  Total after MF                      (1.51, 8.91)
Ennerdale Lake
  Before MF interval                 (16.29, 30.32)
After MF interval
  Commissioning MF                     (0, 18.21)
  Established MF pre-FMDE             (0.09, 20.47)
  Established MF and FMDE             (0.52, 15.57)
  Established MF and post-FMDE         (0, 13.86)
Total after MF                        (0.51, 7.28)
Other sources
  Before MF interval                 (17.03, 29.57)
After MF interval
  Commissioning MF                    (2.53, 35.86)
  Established MF pre-FMDE             (3.38, 31.75)
  Established MF and FMDE             (1.19, 16.86)
  Established MF and post-FMDE        (2.07, 29.40)
  Total after MF                      (5.00, 16.05)

* Time intervals. pre-MF (membrane filtration) March 1, 1996-
February 29, 2000; post-MF March 1, 2000-August 31, 2002. Post-MF
comprises the following: commissioning MF, March 1, 2000-July 31,
2000, established MF before foot and mouth disease epidemic (FMDE),
August 1, 2000-February 20, 2001; established MF and FMDE,
February 21, 2001-January 20, 2002; established MF and post-FMDE,
January 21, 2002-August 3l, 2002.

([dagger]) CI, confidence intervals.

Table 5. Poisson regression model of the incidence of sporadic
cryptosporidiosis *

Predictor             Category       IRR        95% CI         p

Membrane filtration      No       Reference
                         Yes        0.207     0.099-0.431   <0.0001

Foot and mouth           Pre      Reference
disease epidemic       During       0.394     0.167-0.925
                        Post        0.686     0.292-1.612    0.05

Water supply          Crummock    Reference
                      Ennerdale     0.907     0.620-1.329
                        Other       0.820     0.573-1.174    0.6

* IRR, incidence rate ratio; CI, confidence interval.
Goodness-of-fit test (chi square 10.84, 9 df, p = 0.3).

Acknowledgments

We thank colleagues in the steering group and in the many local and national agencies that contributed to this research, in particular, we thank Brian White, Vic Emmerson, Mary Cosgrove, Peter Daley, John Cain, Rachel Horton, Susan Partridge, Judith Hilton, Patrick Wall, Ros Stanwell-Smith, James Stuart, Claire Gilham, Alan Godfree, Matthew Wilkinson, Charmian Kerr, David Counter, Andrew Holliman, John Gray, Tony Lloyd, Mark Smith, David Holt, Joy Graham, Jennifer Clay, Paul Blaylock, Richard Lamb, Dennis Massey, Emma Wigginton, Kristin Elwin, and Anne Thomas.

This study was funded by the Department of Environment, Food and Rural Affairs, Department Health, United Kingdom Water Industry Research Limited and was supervised by the Drinking Water Inspectorate. The Membrane Filtration plant installed in this study was provided by Memcor Ltd. None of the authors has any financial links with Memcor Ltd. No funding was obtained from Memcor Ltd. for this study.

Dr. Goh is an honorary consultant to the Carlisle and District Primary Care Trust and was formerly the consultant in Communicable Disease Control to North Cumbria Health Authority, in northwest England. She specialized in public health medicine and developed an interest in childhood immunization, enteric infection, Cryptosporidium and water supplies.

References

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(4.) Peng MM, Xiao L, Freeman AR, Arrowood MJ, Escalante AA, Weltman AC, et al. Genetic polymorphism among Crvptosporidium parvum isolates: evidence of two distinct human transmission cycles. Emerg Infect Dis. 1997;3:567-73.

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Address for correspondence: Mark Reacher, Health Protection Agency, East of England, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge CB2 2SR, United Kingdom; fax: [phone]; email: [e-mail]

Stella Goh, * Mark Reacher, ([dagger]) David P. Casemore, ([double dagger]) Neville Q. Verlander, ([section]) Andre Charlett, ([section]) Rachel M. Chalmers, ([paragraph]) Margaret Knowles, # Anthony Pennington, * Joy Williams, * Keith Osborn,** and Sarah Richards ([dagger]) ([dagger])

* Carlisle and District Primary Care Trust, Carlisle, United Kingdom;

([dagger]) Health Protection Agency, Cambridge, United Kingdom; ([double dagger]) University of Wales, Aberystwyth, Ceredigion, Wales, United Kingdom; ([section]) Health Protection Agency Centre for Infections, Colindale, London, United Kingdom; ([paragraph]) Singleton Hospital, Swansea, Wales, United Kingdom; # Cumberland Infirmary, Carlisle, United Kingdom; ** United Utilities, Great Sankey, Warrington, United Kingdom; and ([dagger]) ([dagger]) West Cumberland Hospital, Whitehaven, United Kingdom