A Massive Outbreak in Milwaukee of Cryptosporidium Infection Transmitted through the Public Water Supply
William R. Mac Kenzie, Neil J. Hoxie, Mary E. Proctor, M. Stephen
Gradus, Kathleen A. Blair, Dan E. Peterson, James J. Kazmierczak, David
G. Addiss, Kim R. Fox, Joan B. Rose, and Jeffrey P. Davis
Background Early in the spring of 1993 there was a widespreadoutbreak of acute watery diarrhea among the residents of Milwaukee.
Methods We investigated the two Milwaukee water-treatment plants,gathered data from clinical laboratories on the results of testsfor enteric pathogens, and examined ice made during the timeof the outbreak for cryptosporidium oocysts. We surveyed residentswith confirmed cryptosporidium infection and a sample of thosewith acute watery diarrhea consistent with cryptosporidium infection.To estimate the magnitude of the outbreak, we also conducteda survey using randomly selected telephone numbers in Milwaukeeand four surrounding counties.
Results There were marked increases in the turbidity of treatedwater at the city's southern water-treatment plant from March23 until April 9, when the plant was shut down. Cryptosporidiumoocysts were identified in water from ice made in southern Milwaukeeduring these weeks. The rates of isolation of other entericpathogens remained stable, but there was more than a 100-foldincrease in the rate of isolation of cryptosporidium. The medianduration of illness was 9 days (range, 1 to 55). The medianmaximal number of stools per day was 12 (range, 1 to 90). Among285 people surveyed who had laboratory-confirmed cryptosporidiosis,the clinical manifestations included watery diarrhea (in 93percent), abdominal cramps (in 84 percent), fever (in 57 percent),and vomiting (in 48 percent). We estimate that 403,000 peoplehad watery diarrhea attributable to this outbreak.
Conclusions This massive outbreak of watery diarrhea was causedby cryptosporidium oocysts that passed through the filtrationsystem of one of the city's water-treatment plants. Water-qualitystandards and the testing of patients for cryptosporidium werenot adequate to detect this outbreak.
Human infection with cryptosporidium was first documented in19761,2. Since that time, cryptosporidium has been recognizedas a cause of gastrointestinal illness in both immunocompetent3,4,5,6and immunodeficient people6,7. Infection with cryptosporidiumresults in watery diarrhea associated with varying frequenciesof abdominal cramping, nausea, vomiting, and fever. In immunocompetentpeople, cryptosporidiosis is a self-limited illness, but inthose who are immunocompromised, infection can be unrelentingand fatal5,8. Infection occurs in a variety of settings8,9,10,11;waterborne outbreaks of cryptosporidium infection have beendocumented in association with drinking water from a contaminatedartesian well,12 untreated surface water,13 and filtered publicwater supplies14,15,16. We report our investigation of the largestdocumented outbreak of waterborne disease in the United States.
On April 5, 1993, the Wisconsin Division of Health was contactedby the Milwaukee Department of Health after reports of numerouscases of gastrointestinal illness that had resulted in widespreadabsenteeism among hospital employees, students, and schoolteachers.Little information was available about the nature of the illnessor the results of laboratory tests of stool specimens from thosewho were ill. On April 7, two laboratories identified cryptosporidiumoocysts in stool samples from seven adult residents of the Milwaukeearea; none of the laboratories surveyed had found evidence ofincreased or unusual patterns of isolation of any other entericpathogen.
The Milwaukee Water Works (MWW), which obtains water from LakeMichigan, supplies treated water to residences and businessesin the City of Milwaukee and nine surrounding municipalitiesin Milwaukee County. Either of two water-treatment plants, onelocated in the northern part of the city, and the other in thesouthern part, can supply water to the entire district; however,when both plants are in operation, the southern plant predominantlyserves the southern portion of the district.
Examination of the two plants' records on the quality of untreatedwater (intake) and treated water (that supplied to customers)revealed an increase in the turbidity of treated water fromthe southern plant, beginning approximately on March 21, withincreases to unprecedented levels of turbidity from March 23through April 5. These findings pointed to the water supplyas the likely source of infection and led to the institution,on the evening of April 7, of an advisory to MWW customers toboil their water. The southern plant was temporarily closedon April 9.
Methods
Investigation of Water-Treatment Plants
The policies, procedures, and physical plant of the southernMWW facility were reviewed and inspected in April 1993. Dataon the monthly maximal turbidity of untreated and treated waterfrom both plants were reviewed and analyzed for the period fromJanuary 1983 through April 1993. Data on the daily maximal turbidityand coliform count in untreated and treated water, as well asthe pH and temperature of untreated water, were analyzed forthe period from February through April 1993.
Examination of Ice Made during the Outbreak
Water that had been frozen and stored by a southern Milwaukeecompany in 213-liter blocks on March 25 and April 9, 1993, wasmelted and examined. From ice produced on each of those dates,three aliquots of water totaling 639 liters (three melted blocks)were filtered with peristaltic pumps and two types of filter:spun-polypropylene cartridge filters with a nominal porosityof 1 microm (approximate flow rate, 4 liters per minute), and29.2-cm Millipore filters with a porosity of 0.45 microm (approximateflow rate, 2 liters per minute). The filters were eluted, theeluates centrifuged, and the pellets resuspended with the useof a standard procedure; the suspensions were examined for cryptosporidiumoocysts with an immunofluorescent technique17.
Laboratory Surveillance
On April 7, surveillance for enteric pathogens was begun among14 clinical laboratories in Milwaukee County. The laboratoriesreported the retrospective (March 1 through April 6, 1993) andprospective (April 7 through 16, 1993) test results for allstool specimens submitted for bacterial or viral culture andexamination for ova and parasites. All 14 laboratories routinelytested all stool specimens submitted for bacterial culture forsalmonella, shigella, and campylobacter, at a minimum. At ourrequest, the laboratories reported, both retrospectively andprospectively, all positive tests for cryptosporidium from March1 through May 30. Before April 7, 12 of the 14 laboratoriestested for cryptosporidium only at the request of a physician;beginning on April 7, these 12 laboratories began to test allstool specimens for this coccidian protozoan. Cryptosporidiumtesting was performed according to standard concentration techniqueswith either modified acid-fast staining18 (13 laboratories)or direct fluorescent antibody staining19 (1 laboratory).
Examination for Enteric Infection
On April 13, stool specimens were solicited from 11 Milwaukeeresidents with gastrointestinal illness that had begun withinthe previous 48 hours. Stool specimens from these residentswere tested for enteric pathogens with the use of routine proceduresfor enteric bacterial and viral culture, examination for ovaand parasites, and modified acid-fast staining after formalin-ethersedimentation. The stool specimens were examined by electronmicroscopy. Serum samples obtained during the acute and convalescentphases of illness in 8 of the 11 residents were tested for antibodyto the Norwalk virus20.
Laboratory-Confirmed Cryptosporidium Infection
A total of 739 people were found to have cryptosporidium instool samples tested by the 14 participating laboratories betweenMarch 1 and May 30. Telephone numbers were available for 567(77 percent) of these 739 people with laboratory-confirmed cryptosporidiuminfection, and 312 (55 percent) were interviewed by telephone.Of these 312 people, 285 (91 percent) reported an onset of illnessbetween March 1 and May 15, 1993, and were considered case patients;the other 27 people were excluded from the study because theirillnesses had begun before March 1. Telephone interviews werecompleted during two periods: from April 9 through April 13(phase 1), 101 case patients were interviewed; and from April17 through June 2 (phase 2), 200 were interviewed, including16 of those who had been interviewed during phase 1. The samequestionnaire was used in both phases to collect informationon demographic characteristics and clinical illness. Duringthe second phase, however, additional questions were asked aboutpreexisting chronic diseases, weight loss, recurrent diarrhea,and length of hospital stay. People were considered to be immunocompromisedif they reported having had a positive test for the human immunodeficiencyvirus or if they were being treated with immunosuppressive drugs,cancer chemotherapy, radiation therapy, or renal dialysis.
Clinical Cryptosporidium Infection in the MWW Service Area
To determine representative clinical characteristics of illnessamong the people affected by the outbreak, a telephone surveywas conducted on April 9, 10, and 12 with the use of randomlyselected telephone numbers from the MWW service area. The firstadult ( 18 years of age) to answer the telephone was interviewedwith the same questionnaire used in phase 1 to collect demographicand clinical information from the people with laboratory-confirmedcryptosporidiosis. Survey respondents were identified as havingclinical cryptosporidium infection if they reported the occurrenceof watery diarrhea between March 1, 1993, and the time of theinterview.
Survey of Households in the Greater Milwaukee Area
To determine the extent of the outbreak, we conducted a telephonesurvey of households in the greater Milwaukee area (MilwaukeeCounty and the four surrounding counties) with the use of arandom-digit dialing method21,22. Households in the sample werecontacted by interviewers from the Wisconsin Survey ResearchLaboratory during the period from April 28 through May 2. Foreach household, the interviewer asked to speak with the personmost knowledgeable about the health of all members of the household.For each household member, this person provided informationabout demographic characteristics; employment or school attendanceoutside the home; the ZIP Code of the residence and workplaceor school; the occurrence of diarrhea since March 1, 1993; andthe onset, duration, and character of the diarrhea. We defineda case of probable cryptosporidium infection as the onset ofwatery diarrhea during the period from March 1 through April28, 1993.
The residential ZIP Code was used to assign each person in thesurvey to one of four regions. The southern region was definedas the region that received water predominantly from the southernwater-treatment plant, the northern region as that receivingwater predominantly from the northern plant, and the middlezone as that receiving water from either plant, depending onsupply and demand. In our analysis, all three of these regionswere considered part of the MWW service area. All surveyed areasnot receiving MWW water were considered in aggregate as thenon-MWW region.
Results
Investigation of Water-Treatment Plants
At the time of the outbreak, both MWW plants treated water byadding chlorine and polyaluminum chloride (a coagulant to enhancethe formation of larger particulates), rapid mixing, mechanicalflocculation (which promotes the aggregation of particulatesto form floc), sedimentation, and rapid sand filtration. Afterfiltration, the effluent (treated water) was stored in a largeclear well until it was supplied to customers. Filters werecleaned by backwashing them with water, which was then recycledthrough the treatment process.
From January 1983 through January 1993, the turbidity of treatedwater at the southern plant did not exceed 0.4 nephelometricturbidity unit (NTU). During the period from February throughApril 1993, the turbidity of treated water at the southern plantdid not exceed 0.25 NTU until March 18, when it increased to0.35 NTU. From March 23 to April 1, the maximal daily turbidityof treated water was consistently 0.45 NTU or higher, with peaksof 1.7 NTU on March 28 and 30, despite an adjustment of thedose of polyaluminum chloride (Figure 1). Although marked improvementin the turbidity of treated water had been achieved by April1 with the use of polyaluminum chloride, on April 2 the southernplant began to use alum instead of polyaluminum chloride asa coagulant. On April 5, the turbidity of treated water increasedto 1.5 NTU. During the period from February through April 1993,the turbidity of treated water at the northern plant did notexceed 0.45 NTU. There was no correlation between the turbidityof treated water and the turbidity or temperature of untreatedwater.
Figure 1. Maximal Turbidity of Treated Water
in the Northern and Southern Water-Treatment Plants of the Milwaukee
Water Works from March 1 through April 28, 1993.
NTU denotes nephelometric turbidity units.
Throughout the period from February to April 1993, samples oftreated water from both plants were negative for coliforms andwere within the limits set by the Wisconsin Department of NaturalResources for water quality. Inspection of the southern plantrevealed that a streaming-current monitor, which can aid plantoperators in adjusting the dose of coagulant, had been incorrectlyinstalled and thus was not in use. In addition, monitors designedfor continuous measurement of the turbidity of filtered waterwere not in operation. Turbidity was monitored once every eighthours.
Examination of Ice Made during the Outbreak
Water obtained by melting ice blocks produced on March 25 andApril 9, 1993, contained cryptosporidium in concentrations of13.2 and 6.7 oocysts per 100 liters, respectively, when filteredthrough a membrane filter with an absolute porosity of 0.45microm and 2.6 and 0.7 oocysts per 100 liters, respectively,when filtered through a polypropylene cartridge filter witha nominal porosity of 1 microm.
Laboratory Surveillance
During the period from March 1 through April 16, 1993, a totalof 2300 stool specimens were submitted to the 14 clinical laboratoriesin the Milwaukee vicinity for routine culture for bacterialenteric pathogens. Twenty specimens (0.9 percent) were positivefor salmonella, 10 (0.4 percent) for shigella, and 11 (0.5 percent)for campylobacter; 1 of 80 specimens (1.3 percent) culturedfor yersinia and 1 of 73 (1.4 percent) cultured for aeromonaswere positive. During the same period, 14 of 1744 stool specimensexamined for ova and parasites (0.8 percent) were found to havegiardia, and 5 of 266 specimens cultured for enteric viruses(2 percent) were positive. An enzyme immunoassay kit for rotaviruswas used to test 96 specimens, 3 of which (3 percent) were positive.From March 1 through April 6, 12 of 42 stool specimens (29 percent)tested for cryptosporidium were positive; from April 8 throughApril 16, 331 of 1009 specimens (33 percent) were positive.We found no evidence of cyclospora infection. Oocysts examinedby the Centers for Disease Control and Prevention were 4 to6 microm in diameter and were positive for cryptosporidium withmonoclonal-antibody staining.
Examination for Enteric Infection
Cryptosporidium was identified in stool specimens from 8 ofthe 11 people with gastrointestinal illness (73 percent) whosespecimens were obtained within 48 hours after the onset of illness.Stool cultures for enteric bacterial and viral pathogens, electronmicroscopical studies, and stool examination for other ova andparasites, including cyclospora and microsporida, were negative.None of the pairs of serum samples (obtained during the acuteand convalescent phases of illness) had a fourfold rise in antibodyto the Norwalk virus.
Laboratory-Confirmed Cryptosporidium Infection
Of the 285 patients with laboratory-confirmed cryptosporidiuminfection, 170 (60 percent) were female, 130 (46 percent) werehospitalized during the course of their illness, and 48 (17percent) were immunocompromised; their mean age was 41 years(range, 2 months to 93 years). All 285 patients had diarrhea,and 265 (93 percent) characterized it as watery (Table 1). Themedian duration of diarrhea was 9 days (range, 1 to 55), witha median reported maximum of 12 stools per day (range, 1 to90). Among people with fever, the median reported maximal temperaturewas 38.3 °C (101 °F) (range, 37.2 to 40.5 °C [99to 105 °F]). The date of the onset of illness was availablefor 254 confirmed cases with an onset during the period fromMarch 1 through April 15 (Figure 2, upper panel).
Figure 2. Reported Date of the Onset of
Illness in Cases of Laboratory-Confirmed or Clinically Defined
Cryptosporidium Infection during the Period from March 1 through April
15, 1993.
The clinically defined cases were identified during a telephone survey
begun on April 9 of residents in the area served by the Milwaukee Water
Works.
Of the 200 patients with laboratory-confirmed infection whowere interviewed with the longer questionnaire, 150 (75 percent)reported weight loss, with a median loss of 4.5 kg (10 lb) (range,0.45 to 18 kg [1 to 40 lb]), and 81 (41 percent) were hospitalizedwith cryptosporidium infection for a median of 5 days (range,1 to 55). Seventy-seven patients (39 percent) reported a recurrenceof diarrhea after at least 2 days of normal stools, with a medianinterval of 2 days of normal stools (range, 2 to 14) beforethe diarrhea recurred. Recurrence of diarrhea after at leastfive days of normal stools was reported by 11 (6 percent) ofthe patients.
In general, the frequencies of signs and symptoms of illnesswere similar in immunocompromised and immunocompetent patients.However, the immunocompromised patients had more diarrheal stoolsper day (mean, 15 vs. 12; P = 0.08 by the Kruskal-Wallis test),were more likely to be hospitalized (odds ratio, 1.9; 95 percentconfidence interval, 0.95 to 3.9; P = 0.07), and were less likelyto have a recurrence of diarrhea after at least two days ofnormal stools (odds ratio, 0.5; 95 percent confidence interval,0.2 to 1.1; P = 0.09).
Clinical Cryptosporidium Infection in the MWW Service Area
Of the 482 respondents to the telephone survey of the MWW servicearea, 235 (49 percent) reported having had diarrhea since March1, 1993; 201 of the 235 (86 percent) had watery diarrhea andthus met our case definition of clinical cryptosporidiosis.The mean age of the people with clinical cryptosporidiosis was45 years (range, 18 to 84), and 138 (69 percent) were women.The rate of watery diarrhea was similar among men and women.Table 1 shows the clinical characteristics of the people withclinical cryptosporidiosis, as compared with those of the peoplewith laboratory-confirmed cryptosporidium infection. Those withlaboratory-confirmed infection had a significantly longer durationof diarrhea and more stools per day; the frequency of fever,fatigue, nausea, vomiting, and loss of appetite was also higherin this group. Among people with clinical cryptosporidiosis,the median duration of watery diarrhea was 3 days (range, 1to 38), with a median reported maximum of 5 stools per day (range,1 to 60). Among people with fever, the median reported maximaltemperature was 37.7 °C (range, 37.2 to 40.0 °C). Thirteenpeople with clinical cryptosporidiosis (6.5 percent) reportedhaving visited a physician because of their illness. The datesof the onset of illness in those with clinical cryptosporidiuminfection are shown in Figure 2, lower panel.
Survey of Households in the Greater Milwaukee Area
Illness in the Survey Sample
Interviews were completed for 613 of the 840 households thatwere contacted (73 percent). The surveyed households were verysimilar to the 601,458 households reported in the 1990 Census,in terms of the sex, age, and geographic distributions of peoplein the greater Milwaukee area and the number of members perhousehold. Among the 1663 household members surveyed, 493 (30percent) were reported to have had diarrhea beginning duringthe period from March 1 through April 28, 1993, and in 436 thediarrhea was characterized as watery. Among these 436 people,the median duration of diarrhea was 3 days (range, 1 to 45).The occurrence of diarrhea among survey participants peakedfrom April 3 through April 5, and by April 16 it had decreasedto the level before the outbreak (Figure 3). The attack ratewas similar for males and females and was highest among householdmembers who were 30 to 39 years of age (Table 2).
Figure 3. Reported Date of the Onset of Watery
Diarrhea during the Period from March 1 through April 28, 1993, in 436
Cases of Infection Identified by a Random-Digit Telephone Survey of the
Greater Milwaukee Area.
Table 2. Rate of Watery Diarrhea from March 1
through April 28, 1993, among Respondents in a Random-Digit Telephone
Survey of Households in the Greater Milwaukee Area, According to Sex,
Age, and Water Works Region.
The rate of watery diarrhea was highest among the residentsof the MWW southern region (52 percent), less high in the middlezone (33 percent) and northern region (26 percent), and lowestoutside the MWW service area (15 percent) (Table 2). The riskof watery diarrhea was higher among residents of the MWW servicearea than among residents of areas outside the MWW region (relativerisk, 2.7; 95 percent confidence interval, 2.2 to 3.2; P<0.001).As compared with the risk of watery diarrhea among people livingoutside the MWW service area, the risk was more than three timeshigher among residents of the MWW southern region (relativerisk, 3.6; 95 percent confidence interval, 3.0 to 4.3; P<0.001),more than two times higher among those in the middle zone (relativerisk, 2.4; 95 percent confidence interval, 1.8 to 3.3; P<0.001),and almost two times higher among those in the northern region(relative risk, 1.8; 95 percent confidence interval, 1.39 to2.3; P<0.001). Among the 644 people who resided outside theMWW service area and worked outside the home, 11 of the 28 (39percent) who worked in the southern region had watery diarrhea,as compared with 94 of the 616 (15 percent) who worked outsidethe southern region (relative risk, 2.6; 95 percent confidenceinterval, 1.6 to 4.2; P = 0.002).
Estimate of the Magnitude of the Outbreak
By applying the rate of watery diarrhea among the survey participants(26 percent) to the total population of the greater Milwaukeearea (1,610,000 people), we estimated that 419,000 people (95percent confidence interval, 386,000 to 451,000) in this areahad watery diarrhea during the survey period. Using a backgroundrate of 0.5 percent per month for cases of watery diarrhea amongresidents, we estimated that 16,000 cases of watery diarrheaunrelated to the waterborne outbreak could have been expectedduring March and April 1993 (unpublished data). Thus, an estimated403,000 people had watery diarrhea that could be attributedto this outbreak.
Discussion
A massive outbreak of waterborne cryptosporidium infection occurredin the greater Milwaukee area during late March and early April1993. We estimate that more than 400,000 people were affectedduring this outbreak; however, by limiting the case definitionto watery diarrhea in our survey, we may have underestimatedthe size of the affected population. Cryptosporidium infectionwas confirmed in more than 600 people with gastrointestinalillness in association with this outbreak, and despite intensiveinvestigation, no other enteric pathogen could be found to accountfor the illness.
More than half the people who received residential drinkingwater predominantly from the MWW's southern water-treatmentplant became ill, which was twice the rate of illness amongpeople whose residential drinking water came mainly from theMWW's northern water-treatment plant. The intermediate attackrate among residents of the middle zone was expected, sincethe MWW distribution system, adjusting for variations in flow,would have intermittently allowed water from the southern plantto reach their residences. Diarrhea among people not livingin the MWW service area may have resulted from consumption ofwater while they were working in or visiting the area. Amongnursing home residents in the northern region, who were unlikelyto travel, there was no increase in diarrheal illness associatedwith the outbreak, whereas among nursing home residents in thesouthern region, there was a marked increase in the prevalenceof diarrhea (unpublished data).
Our findings demonstrate a wide range in the duration and severityof illness caused by cryptosporidium infection. As expected,people with laboratory-confirmed cryptosporidiosis had diarrheaof significantly longer duration and more frequent bowel movements,vomiting, fever, and fatigue than those with clinical cryptosporidiosiswho were identified through the telephone survey. The epidemiologicfeatures and dates of onset of illness among the people withlaboratory-confirmed cryptosporidium infection were similarto those among the people interviewed by telephone who reportedhaving watery diarrhea, supporting our hypothesis that the lattergroup had clinical cryptosporidiosis.
Despite communitywide increases in diarrheal illness in Milwaukee,the recognition of cryptosporidium infection as the cause ofthis outbreak was delayed for several reasons. The constellationof gastrointestinal symptoms (e.g., diarrhea, abdominal cramping,and nausea) and constitutional signs and symptoms (e.g., fatigue,low-grade fever, muscle aches, and headaches) reported by Milwaukee-arearesidents led many physicians to diagnose viral gastroenteritisor "intestinal flu," without further investigation. Our findingssuggest that people with diarrhea seek health care infrequently,do so only when the illness is severe or prolonged, and areunlikely to be tested for cryptosporidium infection. Unlikethe detection of other intestinal parasites, which are identifiedby means of a standard examination for ova and parasites, thedetection of cryptosporidium requires special testing. Infrequenttesting for cryptosporidium in patients with diarrhea may bedue to misconceptions about the incidence and severity of thisinfection among immunocompetent patients. A large, multicenter,laboratory-based study of patients with acute infectious diarrheain England found that infection with cryptosporidium was almostas common as salmonella infection and nearly three times morecommon than shigella infection23. Although clinicians may questionthe value of testing when infection is self-limited in immunocompetenthosts and no effective treatment is available, testing allowsthe education of patients, facilitates the recognition of anoutbreak, and may lead to the institution of measures to preventthe spread of infection15,16,24.
In the Milwaukee outbreak, cryptosporidium oocysts in untreatedwater from Lake Michigan apparently entered the southern water-treatmentplant and were then inadequately removed by the coagulationand filtration process. Cryptosporidium oocysts have often beenfound in untreated surface water used for public water suppliesin the United States25,26. The source of the oocysts leadingto the outbreak in Milwaukee and the timing of their entranceinto Lake Michigan remain speculative. Possible sources includecattle along two rivers that flow into the Milwaukee harbor,slaughterhouses, and human sewage. Rivers that were swelledby spring rains and snow runoff may have transported oocystsinto Lake Michigan and from there to the intake of the MWW southernplant.
As in previous cryptosporidium outbreaks in the United Statesassociated with filtered water supplies, water-quality measurementsat the MWW southern plant were within the required limits; however,unlike the plants involved in the previous outbreaks, the MWWplant had no evident mechanical breakdown of its flocculatorsor filters14,27. The reason for the plant's failure to maintaintreated water at low turbidity is unclear and continues to beinvestigated. Difficulty in determining the appropriate amountsof polyaluminum chloride and alum may have been a contributingfactor in the failure to maintain low turbidity; the MWW hascorrectly reinstalled the streaming-current monitor, which nowaids in determining the amount of coagulant. The recycling offilter backwash water may increase the concentration of oocystsin water passing through filters; therefore, this practice hasbeen discontinued. Decreased turbidity and removal of particlesunder 15 microm in diameter from water have been shown to correlatesignificantly with the detection of cryptosporidium in water28.The MWW therefore has installed continuous turbidity monitorson each filter bed, with an alarm sounded and the system automaticallyshut down if the turbidity of filtered water exceeds 0.3 NTU,and has instituted frequent measurement of particles in untreatedand treated water.
Because some visitors to the MWW service area who drank verysmall amounts of water ( 240 ml [8 oz]) had laboratory-confirmedcryptosporidiosis (unpublished data), the peak concentrationof oocysts in the water probably far exceeded one oocyst perliter. Thus, we believe the concentration of cryptosporidiumoocysts found in the tested ice vastly underestimates the peaklevel in water from the southern plant. The lower-than-expectedconcentration of oocysts may have been due in part to the timingof the specimen collection (i.e., the freezing of ice blocks),losses during the freeze-thaw process, and insensitivity oftesting procedures29.
The number of both laboratory-confirmed and clinically definedcases of cryptosporidium infection with an onset of illnessbefore March 23, when the turbidity of treated water increased,was higher than expected, suggesting that cryptosporidium oocystshad entered the water supply before the increase in turbiditywas apparent. This occurrence would not be without precedent.In England a waterborne outbreak of cryptosporidium infectionassociated with a filtered water supply occurred while the turbidityof treated water remained less than 0.5 NTU30. Surveillancein the United Kingdom has uncovered sudden, irregular, communitywideincreases in cryptosporidiosis that were unlikely to have beentransmitted by the fecal-oral route, suggesting that some sporadiccases of cryptosporidiosis may be waterborne23.
Cryptosporidiosis is an underdiagnosed condition, and outbreaksare likely to be underrecognized8,18. Our findings have implicationsfor standards of water quality, public health surveillance,and recognition of cryptosporidium outbreaks in the United States.Until an inexpensive, rapid, and sensitive means of detectingand quantifying cryptosporidium in treated water is available,we believe that water-treatment plants should consider institutingcontinuous monitoring of treated water for turbidity, particularlyof filter effluent, and particle size. Plant design and water-treatmentprocedures should be improved to maintain the qaulity of treatedwater at a level that will make the presence of oocysts unlikely(e.g., a goal of turbidity 0.1 NTU). We recommend that cliniciansand laboratories consider performing routine stool tests forcryptosporidium in people with watery diarrhea and that publichealth officials make cryptosporidium infection a reportablecondition. In the United Kingdom, water and health officialshave already developed an extensive strategy to investigatethe clinical importance of cryptosporidium found in water supplies31.Intensive efforts and cooperation between the medical communityand those who provide and regulate drinking water in the UnitedStates will be required to prevent future waterborne outbreakscaused by this emerging pathogen and ensure the safety of drinkingwater for all citizens.
We are indebted to the following people for their contributionsto this study: Walter Powers, A.J. Henry, and Richard R. Regent,Milwaukee Water Works; the infection-control practitioners atparticipating nursing homes and hospitals in the Milwaukee area;the directors and parasitologists at the 14 participating clinicallaboratories in the Milwaukee vicinity; Hon. John Norquist,mayor of the City of Milwaukee; Paul Nannis, director, ThomasSchlenker, M.D., and the staff of public health nurses and administrators,Milwaukee Health Department; Wendy L. Schell, M.A., Helen North,R.N., Jackie Kowalski, R.N., John Chapin, Ivan Imm, and AnnHaney, Wisconsin Division of Health; Ron Tursky and the staffof the Milwaukee STD Program; Carol Graham, R.N., and the volunteerpublic health nurses of the Greater Milwaukee area; Gerald Sedmak,Ph.D., Ajaib Singh, Ph.D., and the staff of the Milwaukee Bureauof Laboratories; Paul Biedrzycki and the staff of the EnvironmentalHealth Section, Milwaukee Health Department; Dennis Juranek,D.V.M., Division of Parasitic Diseases, Center for InfectiousDiseases; Roger Glass, M.D., M.P.H., Ph.D., Stephan S. Monroe,Ph.D., Charles Humphries, Ph.D., and Sara Stine, Centers forDisease Control and Prevention (CDC) Viral GastroenterologyLaboratory; Margaret Hurd and the staff of the CDC ParasitologyLaboratory; the staff of the Wisconsin State Laboratory of Hygiene;the staff of the Survey Research Laboratory, University of WisconsinExtension; Darren Lytle, P.E., U.S. Environmental ProtectionAgency; and Ava Navin, Epidemiology Program Office, CDC.
Source Information
From the Bureau of Public Health, Wisconsin Division of Health, Madison
(W.R.M., N.J.H., M.E.P., J.J.K., J.P.D.); the Epidemiology Program
Office, Division of Field Epidemiology (W.R.M., D.E.P.), Epidemic
Intelligence Service (W.R.M.), Division of Parasitic Diseases, National
Center for Infectious Diseases (D.G.A.), Centers for Disease Control
and Prevention, Atlanta; the City of Milwaukee Department of Health
(K.A.B.) and Bureau of Laboratories (M.S.G.), Milwaukee; the U.S.
Environmental Protection Agency, Cincinnati (K.R.F.); and the
University of South Florida, Tampa (J.B.R.).
Address reprint requests to Dr.
Davis at the Wisconsin Division of Health, Bureau of Public Health,
1400 E. Washington Ave., Rm. 241, Madison, WI 53703.
References
Nime FA, Burek JD, Page DL, Holscher MA, Yardley JH.
Acute enterocolitis in a human being infected with the protozoan
Cryptosporidium. Gastroenterology 1976;70:592-598. [Medline]
Meisel JL, Perera DR, Meligro C, Rubin CE.
Overwhelming watery diarrhea associated with a cryptosporidium in an
immunosuppressed patient. Gastroenterology 1976;70:1156-1160. [Medline]
Jokipii L, Jokipii AMM. Timing of symptoms and oocyst excretion in human cryptosporidiosis. N Engl J Med 1986;315:1643-1647. [Abstract]
Wolfson JS, Richter JM, Waldron MA, Weber DJ,
McCarthy DM, Hopkins CC. Cryptosporidiosis in immunocompetent patients.
N Engl J Med 1985;312:1278-1282. [Abstract]
Fayer R, Ungar BLP. Cryptosporidium spp. and cryptosporidiosis. Microbiol Rev 1986;50:458-483. [Free Full Text]
Current WL, Reese NC, Ernst JV, Bailey WS, Heyman
MB, Weinstein WM. Human cryptosporidiosis in immunocompetent and
immunodeficient persons: studies of an outbreak and experimental
transmission. N Engl J Med 1983;308:1252-1257. [Abstract]
Current WL, Garcia LS. Cryptosporidiosis. Clin Microbiol Rev 1991;4:325-358. [Free Full Text]
Koch KL, Phillips DJ, Aber RC, Current WL.
Cryptosporidiosis in hospital personnel: evidence for person-to-person
transmission. Ann Intern Med 1985;102:593-596.
Alpert G, Bell LM, Kirkpatrick CE, et al. Outbreak of cryptosporidiosis in a day-care center. Pediatrics 1986;77:152-157. [Free Full Text]
Jokipii L, Pohjola S, Jokipii AM.
Cryptosporidiosis associated with traveling and giardiasis.
Gastroenterology 1985;89:838-842. [Medline]
D'Antonio RG, Winn RE, Taylor JP, et al. A
waterborne outbreak of cryptosporidiosis in normal hosts. Ann Intern
Med 1985;103:886-888.
Gallaher MM, Herndon JL, Nims LJ, Sterling CR,
Grabowski DJ, Hull HF. Cryptosporidiosis and surface water. Am J Public
Health 1989;79:39-42. [Free Full Text]
Hayes EB, Matte TD, O'Brien TR, et al. Large
community outbreak of cryptosporidiosis due to contamination of a
filtered public water supply. N Engl J Med 1989;320:1372-1376. [Abstract]
Richardson AJ, Frankenberg RA, Buck AC, et al. An
outbreak of waterborne cryptosporidiosis in Swindon and Oxfordshire.
Epidemiol Infect 1991;107:485-495. [Medline]
Joseph C, Hamilton G, O'Connor M, et al.
Cryptosporidiosis in the Isle of Thanet: an outbreak associated with
local drinking water. Epidemiol Infect 1991;107:509-519. [Medline]
Rose JB, Landeen LK, Riley KR, Gerba CP.
Evaluation of immunofluorescence techniques for detection of
Cryptosporidium oocysts and Giardia cysts from environmental samples.
Appl Environ Microbiol 1989;55:3189-3196. [Free Full Text]
Ma P, Soave R. Three-step stool examination for
cryptosporidiosis in 10 homosexual men with protracted watery diarrhea.
J Infect Dis 1983;147:824-828. [Medline]
Arrowood MJ, Sterling CR. Comparison of
conventional staining methods and monoclonal antibody-based methods for
Cryptosporidium oocyst detection. J Clin Microbiol 1989;27:1490-1495. [Free Full Text]
Jiang X, Wang M, Graham DY, Estes MK. Expression,
self-assembly, and antigenicity of the Norwalk virus capsid protein. J
Virol 1992;66:6527-6532. [Free Full Text]
Palit D, Palit CD. CASS CATI, version 3.0:
computer assisted survey system and computer assisted telephone
interviewing. Madison: University of Wisconsin Extension Program, 1988.
Palit CD, Sharp H. Microcomputer assisted telephone interviewing. Sociol Methods Res 1983;12:169-89.
Public Health Laboratory Service Study Group.
Cryptosporidiosis in England and Wales: prevalence and clinical
epidemiological features. BMJ 1990;300:774-777.
Skeels MR, Sokolow R, Hubbard CV, Andrus JK,
Baisch J. Cryptosporidium infection in Oregon public health clinic
patients 1985-88: the value of statewide laboratory surveillance. Am J
Public Health 1990;80:305-308. [Free Full Text]
LeChevallier MW, Norton WD, Lee RG. Occurrence of
Giardia and Cryptosporidium spp. in surface water supplies. Appl
Environ Microbiol 1991;57:2610-2616. [Erratum, Appl Environ Microbiol
1992;58:780.] [Free Full Text]
Rose JB, Gerba CP, Jakubowski W. Survey of potable
water supplies for Cryptosporidium and Giardia. Environ Sci Technol
1991;25:1393-400.
Leland D, McAnulty J, Keene W, Sterens G. A
cryptosporidiosis outbreak in a filtered-water supply. J Am Water Works
Assoc 1993;85:34-42.
LeChevallier MW, Norton WD, Lee RG. Giardia and
Cryptosporidium spp. in filtered drinking water supplies. Appl Environ
Microbiol 1991;57:2617-2621. [Free Full Text]
Rose JB. Environmental sampling for waterborne
pathogens: overview of methods, application limitations and data
interpretation. In: Craun GF, ed. Methods for the investigation and
prevention of waterborne disease outbreaks. Cincinnati: Health Effects
Research Laboratory, Environmental Protection Agency, 1990:223-34.
Colbourne JS. Thames utilities experience with
Cryptosporidium. In: Proceedings of the American Water Works
Association Water Quality Technology Conference, Philadelphia, November
12-15, 1989. Denver: American Water Works Association, 1989:275-86.
Badenoch J. Cryptosporidium in water supplies. London: Her Majesty's Stationery Office, 1990.
Gait, R., Soutar, R. H., Hanson, M., Fraser, C., Chalmers, R.
(2008). Outbreak of cryptosporidiosis among veterinary students. Vet Rec.
162: 843-845
[Abstract][Full Text]
Dong, J., Olano, J. P., McBride, J. W., Walker, D. H.
(2008). Emerging Pathogens: Challenges and Successes of Molecular Diagnostics. J. Mol. Diagn.
10: 185-197
[Abstract][Full Text]
Frazar,
C. D., Orlandi, P. A. (2007). Evaluation of Two DNA Template
Preparation Methods for Post-Immunomagnetic Separation Detection of
Cryptosporidium parvum in Foods and Beverages by PCR. Appl. Environ. Microbiol.
73: 7474-7476
[Abstract][Full Text]
PARR,
J. B., SEVILLEJA, J. E., AMIDOU, S., ALCANTARA, C., STROUP, S. E.,
KOHLI, A., FAYER, R., LIMA, A. A. M., HOUPT, E. R., GUERRANT, R. L.
(2007). DETECTION AND QUANTIFICATION OF CRYPTOSPORIDIUM IN HCT-8 CELLS
AND HUMAN FECAL SPECIMENS USING REAL-TIME POLYMERASE CHAIN REACTION. Am J Trop Med Hyg
76: 938-942
[Abstract][Full Text]
Marquet,
P., Barbot, L., Plante, A., Huneau, J. F., Gobert, J. G., Kapel, N.
(2007). Cryptosporidiosis Induces a Transient Upregulation of the
Oligopeptides Transporter (PepT1) Activity in Neonatal Rats. Exp. Biol. Med.
232: 454-460
[Abstract][Full Text]
Snelling,
W. J., Lin, Q., Moore, J. E., Millar, B. C., Tosini, F., Pozio, E.,
Dooley, J. S. G., Lowery, C. J. (2007). Proteomics Analysis and Protein
Expression during Sporozoite Excystation of Cryptosporidium parvum
(Coccidia, Apicomplexa). Mol. Cell. Proteomics
6: 346-355
[Abstract][Full Text]
Morsy El-Senousy, W., Guix, S., Abid, I., Pinto, R. M., Bosch, A.
(2007). Removal of Astrovirus from Water and Sewage Treatment Plants, Evaluated by a Competitive Reverse Transcription-PCR. Appl. Environ. Microbiol.
73: 164-167
[Abstract][Full Text]
Feltus, D. C., Giddings, C. W., Schneck, B. L., Monson, T., Warshauer, D., McEvoy, J. M.
(2006). Evidence Supporting Zoonotic Transmission of Cryptosporidium spp. in Wisconsin. J. Clin. Microbiol.
44: 4303-4308
[Abstract][Full Text]
Starkey, S. R., Kimber, K. R., Wade, S. E., Schaaf, S. L., White, M. E., Mohammed, H. O.
(2006). Risk factors associated with Cryptosporidium infection on dairy farms in a New York State watershed.. J DAIRY SCI
89: 4229-4236
[Abstract][Full Text]
Searcy, K. E., Packman, A. I., Atwill, E. R., Harter, T.
(2006). Capture and Retention of Cryptosporidium parvum Oocysts by Pseudomonas aeruginosa Biofilms. Appl. Environ. Microbiol.
72: 6242-6247
[Abstract][Full Text]
Berger, M., Shiau, R., Weintraub, J. M
(2006). Review of syndromic surveillance: implications for waterborne disease detection.. J. Epidemiol. Community Health
60: 543-550
[Abstract][Full Text]
Watson, C.
(2006). The importance of safe drinking water and sanitary systems for human health and well-being: a personal view. BUILDING SERV ENG RES TECHNOL
27: 85-89
Searcy, K. E., Packman, A. I., Atwill, E. R., Harter, T.
(2006). Deposition of cryptosporidium oocysts in streambeds.. Appl. Environ. Microbiol.
72: 1810-1816
[Abstract][Full Text]
Cohen,
S., Dalle, F., Gallay, A., Di Palma, M., Bonnin, A., Ward, H. D.
(2006). Identification of Cpgp40/15 Type Ib as the Predominant Allele
in Isolates of Cryptosporidium spp. from a Waterborne Outbreak of
Gastroenteritis in South Burgundy, France. J. Clin. Microbiol.
44: 589-591
[Abstract][Full Text]
Kuczynska, E., Shelton, D. R., Pachepsky, Y.
(2005). Effect of Bovine Manure on Cryptosporidium parvum Oocyst Attachment to Soil. Appl. Environ. Microbiol.
71: 6394-6397
[Abstract][Full Text]
ONG,
C. S., LI, A. S., PRIEST, J. W., COPES, R., KHAN, M., FYFE, M. W.,
MARION, S. A., ROBERTS, J. M., LAMMIE, P. J., ISAAC-RENTON, J. L.
(2005). ENZYME IMMUNOASSAY OF CRYPTOSPORIDIUM-SPECIFIC IMMUNOGLOBULIN G
ANTIBODIES TO ASSESS LONGITUDINAL INFECTION TRENDS IN SIX COMMUNITIES
IN BRITISH COLUMBIA, CANADA. Am J Trop Med Hyg
73: 288-295
[Abstract][Full Text]
Johnson, A. M., Linden, K., Ciociola, K. M., De Leon, R., Widmer, G., Rochelle, P. A.
(2005). UV Inactivation of Cryptosporidium hominis as Measured in Cell Culture. Appl. Environ. Microbiol.
71: 2800-2802
[Abstract][Full Text]
Coupe,
S., Sarfati, C., Hamane, S., Derouin, F. (2005). Detection of
Cryptosporidium and Identification to the Species Level by Nested PCR
and Restriction Fragment Length Polymorphism. J. Clin. Microbiol.
43: 1017-1023
[Abstract][Full Text]
Ochiai,
Y., Takada, C., Hosaka, M. (2005). Detection and Discrimination of
Cryptosporidium parvum and C. hominis in Water Samples by
Immunomagnetic Separation-PCR. Appl. Environ. Microbiol.
71: 898-903
[Abstract][Full Text]
Sedmak,
G., Bina, D., MacDonald, J., Couillard, L. (2005). Nine-Year Study of
the Occurrence of Culturable Viruses in Source Water for Two Drinking
Water Treatment Plants and the Influent and Effluent of a Wastewater
Treatment Plant in Milwaukee, Wisconsin (August 1994 through July
2003). Appl. Environ. Microbiol.
71: 1042-1050
[Abstract][Full Text]
Searcy, K. E., Packman, A. I., Atwill, E. R., Harter, T.
(2005). Association of Cryptosporidium parvum with Suspended Particles: Impact on Oocyst Sedimentation. Appl. Environ. Microbiol.
71: 1072-1078
[Abstract][Full Text]
Eisenberg,
J. N. S., Lei, X., Hubbard, A. H., Brookhart, M. A., Colford, J. M. Jr.
(2005). The Role of Disease Transmission and Conferred Immunity in
Outbreaks: Analysis of the 1993 Cryptosporidium Outbreak in Milwaukee,
Wisconsin. Am J Epidemiol
161: 62-72
[Abstract][Full Text]
Musher, D. M., Musher, B. L.
(2004). Contagious Acute Gastrointestinal Infections. NEJM
351: 2417-2427
[Full Text]
Lee, L. Y., Ong, S. L., Hu, J. Y., Ng, W. J., Feng, Y., Tan, X., Wong, S. W.
(2004). Use of Semiconductor Quantum Dots for Photostable Immunofluorescence Labeling of Cryptosporidium parvum. Appl. Environ. Microbiol.
70: 5732-5736
[Abstract][Full Text]
Osterberg, D., Wallinga, D.
(2004). Addressing Externalities From Swine Production to Reduce Public Health and Environmental Impacts. Am. J. Public Health
94: 1703-1708
[Abstract][Full Text]
Villena,
I., Aubert, D., Gomis, P., Ferte, H., Inglard, J.-C., Denis-Bisiaux,
H., Dondon, J.-M., Pisano, E., Ortis, N., Pinon, J.-M. (2004).
Evaluation of a Strategy for Toxoplasma gondii Oocyst Detection in
Water. Appl. Environ. Microbiol.
70: 4035-4039
[Abstract][Full Text]
Roy,
S. L., DeLong, S. M., Stenzel, S. A., Shiferaw, B., Roberts, J. M.,
Khalakdina, A., Marcus, R., Segler, S. D., Shah, D. D., Thomas, S.,
Vugia, D. J., Zansky, S. M., Dietz, V., Beach, M. J. (2004). Risk
Factors for Sporadic Cryptosporidiosis among Immunocompetent Persons in
the United States from 1999 to 2001. J. Clin. Microbiol.
42: 2944-2951
[Abstract][Full Text]
Zaalouk, T. K., Bajaj-Elliott, M., George, J. T., McDonald, V.
(2004). Differential Regulation of {beta}-Defensin Gene Expression during Cryptosporidium parvum Infection. Infect. Immun.
72: 2772-2779
[Abstract][Full Text]
Wohlsen,
T., Bates, J., Gray, B., Katouli, M. (2004). Evaluation of Five
Membrane Filtration Methods for Recovery of Cryptosporidium and Giardia
Isolates from Water Samples. Appl. Environ. Microbiol.
70: 2318-2322
[Abstract][Full Text]
Darnault,
C. J. G., Steenhuis, T. S., Garnier, P., Kim, Y.-J., Jenkins, M. B.,
Ghiorse, W. C., Baveye, P. C., Parlange, J.-Y. (2004). Preferential
Flow and Transport of Cryptosporidium parvum Oocysts through the Vadose
Zone: Experiments and Modeling. Vadose Zone J
3: 262-270
[Abstract][Full Text]
Xiao, L., Fayer, R., Ryan, U., Upton, S. J.
(2004). Cryptosporidium Taxonomy: Recent Advances and Implications for Public Health. Clin. Microbiol. Rev.
17: 72-97
[Abstract][Full Text]
Priest, J. W., Mehlert, A., Arrowood, M. J., Riggs, M. W., Ferguson, M. A. J.
(2003). Characterization of a Low Molecular Weight Glycolipid Antigen from Cryptosporidium parvum. J. Biol. Chem.
278: 52212-52222
[Abstract][Full Text]
Sedmak,
G., Bina, D., MacDonald, J. (2003). Assessment of an Enterovirus Sewage
Surveillance System by Comparison of Clinical Isolates with Sewage
Isolates from Milwaukee, Wisconsin, Collected August 1994 to December
2002. Appl. Environ. Microbiol.
69: 7181-7187
[Abstract][Full Text]
Fawell, J., Nieuwenhuijsen, M. J
(2003). Contaminants in drinking water: Environmental pollution and health. Br Med Bull
68: 199-208
[Abstract][Full Text]
Hogan, W. R., Tsui, F.-C., Ivanov, O., Gesteland, P. H., Grannis, S., Overhage, J. M., Robinson, J. M., Wagner, M. M.
(2003). Detection of Pediatric Respiratory and Diarrheal Outbreaks from Sales of Over-the-counter Electrolyte Products. J. Am. Med. Inform. Assoc.
10: 555-562
[Abstract][Full Text]
Hellard, M, Hocking, J, Willis, J, Dore, G, Fairley, C
(2003). Risk factors leading to Cryptosporidium infection in men who have sex with men. Sex. Transm. Infect.
79: 412-414
[Abstract][Full Text]
Greenberg, M., Mayer, H., Miller, K. T., Hordon, R., Knee, D.
(2003). Reestablishing Public Health and Land Use Planning to Protect Public Water Supplies. Am. J. Public Health
93: 1522-1526
[Abstract][Full Text]
Gaffield, S. J., Goo, R. L., Richards, L. A., Jackson, R. J.
(2003). Public Health Effects of Inadequately Managed Stormwater Runoff. Am. J. Public Health
93: 1527-1533
[Abstract][Full Text]
Gennaccaro, A. L., McLaughlin, M. R., Quintero-Betancourt, W., Huffman, D. E., Rose, J. B.
(2003). Infectious Cryptosporidium parvum Oocysts in Final Reclaimed Effluent. Appl. Environ. Microbiol.
69: 4983-4984
[Abstract][Full Text]
Butkus, M. A., Bays, J. T., Labare, M. P.
(2003). Influence of Surface Characteristics on the Stability of Cryptosporidium parvum Oocysts. Appl. Environ. Microbiol.
69: 3819-3825
[Abstract][Full Text]
Chick, S. E., Soorapanth, S., Koopman, J. S.
(2003). Inferring Infection Transmission Parameters That Influence Water Treatment Decisions. Management Science
49: 920-935
[Abstract]
Kahn, L. H.
(2003). A Prescription For Change: The Need For Qualified Physician Leadership In Public Health. Health Aff (Millwood)
22: 241-248
[Abstract][Full Text]
Feng, Y. Y., Ong, S. L., Hu, J. Y., Song, L. F., Tan, X. L., Ng, W. J.
(2003). Effect of Particles on the Recovery of Cryptosporidium Oocysts from Source Water Samples of Various Turbidities. Appl. Environ. Microbiol.
69: 1898-1903
[Abstract][Full Text]
Lashley, F. R.
(2003). Factors Contributing to the Occurrence of Emerging Infectious Diseases. Biol Res Nurs
4: 258-267
[Abstract]
Guan, T. Y., Holley, R. A.
(2003). Pathogen Survival in Swine Manure Environments and Transmission of Human Enteric Illness--A Review. J. Environ. Qual.
32: 383-392
[Abstract][Full Text]
Cole, J., Blikslager, A., Hunt, E., Gookin, J., Argenzio, R.
(2003). Cyclooxygenase blockade and exogenous glutamine enhance sodium absorption in infected bovine ileum. Am. J. Physiol. Gastrointest. Liver Physiol.
284: G516-G524
[Abstract][Full Text]
Garcia,
L. S., Shimizu, R. Y., Novak, S., Carroll, M., Chan, F. (2003).
Commercial Assay for Detection of Giardia lamblia and Cryptosporidium
parvum Antigens in Human Fecal Specimens by Rapid Solid-Phase
Qualitative Immunochromatography. J. Clin. Microbiol.
41: 209-212
[Abstract][Full Text]
Dai, X., Boll, J.
(2003). Evaluation of Attachment of Cryptosporidium parvum and Giardia lamblia to Soil Particles. J. Environ. Qual.
32: 296-304
[Abstract][Full Text]
Rochelle, P. A., Marshall, M. M., Mead, J. R., Johnson, A. M., Korich, D. G., Rosen, J. S., De Leon, R.
(2002). Comparison of In Vitro Cell Culture and a Mouse Assay for Measuring Infectivity of Cryptosporidium parvum. Appl. Environ. Microbiol.
68: 3809-3817
[Abstract][Full Text]
Chen, X.-M., Keithly, J. S., Paya, C. V., LaRusso, N. F.
(2002). Cryptosporidiosis. NEJM
346: 1723-1731
[Full Text]
Widmer, K. W., Oshima, K. H., Pillai, S. D.
(2002). Identification of Cryptosporidium parvum Oocysts by an Artificial Neural Network Approach. Appl. Environ. Microbiol.
68: 1115-1121
[Abstract][Full Text]
Jellison, K. L., Hemond, H. F., Schauer, D. B.
(2002). Sources and Species of Cryptosporidium Oocysts in the Wachusett Reservoir Watershed. Appl. Environ. Microbiol.
68: 569-575
[Abstract][Full Text]
Kuhn, R. C., Rock, C. M., Oshima, K. H.
(2002). Occurrence of Cryptosporidium and Giardia in Wild Ducks along the Rio Grande River Valley in Southern New Mexico. Appl. Environ. Microbiol.
68: 161-165
[Abstract][Full Text]
Hunter, P. R., Nichols, G.
(2002). Epidemiology and Clinical Features of Cryptosporidium Infection in Immunocompromised Patients. Clin. Microbiol. Rev.
15: 145-154
[Abstract][Full Text]
Katanik,
M. T., Schneider, S. K., Rosenblatt, J. E., Hall, G. S., Procop, G. W.
(2001). Evaluation of ColorPAC Giardia/Cryptosporidium Rapid Assay and
ProSpecT Giardia/Cryptosporidium Microplate Assay for Detection of
Giardia and Cryptosporidium in Fecal Specimens. J. Clin. Microbiol.
39: 4523-4525
[Abstract][Full Text]
LINGER, J. B., MOLINARI, J. A., FORBES, W. C., FARTHING, C. F., WINGET, W. J.
(2001). Evaluation of a hydrogen peroxide disinfectant for dental unit waterlines. Journal of the American Dental Association
132: 1287-1291
[Abstract][Full Text]
Curriero, F. C., Patz, J. A., Rose, J. B., Lele, S.
(2001). The Association Between Extreme Precipitation and Waterborne Disease Outbreaks in the United States, 1948-1994. Am. J. Public Health
91: 1194-1199
[Abstract][Full Text]
Duggan, C. P., Misdraji, J.
(2001). Case 23-2001- An 18-Month-Old Girl with Persistent Diarrhea and Malnutrition. NEJM
345: 276-281
[Full Text]
Sturbaum,
G. D., Reed, C., Hoover, P. J., Jost, B. H., Marshall, M. M., Sterling,
C. R. (2001). Species-Specific, Nested PCR-Restriction Fragment Length
Polymorphism Detection of Single Cryptosporidium parvum Oocysts. Appl. Environ. Microbiol.
67: 2665-2668
[Abstract][Full Text]
Priest,
J. W., Li, A., Khan, M., Arrowood, M. J., Lammie, P. J., Ong, C. S.,
Roberts, J. M., Isaac-Renton, J. (2001). Enzyme Immunoassay Detection
of Antigen-Specific Immunoglobulin G Antibodies in Longitudinal Serum
Samples from Patients with Cryptosporidiosis. CVI
8: 415-423
[Abstract][Full Text]
Simmons,
O. D. III, Sobsey, M. D., Heaney, C. D., Schaefer, F. W. III, Francy,
D. S. (2001). Concentration and Detection of Cryptosporidium Oocysts in
Surface Water Samples by Method 1622 Using Ultrafiltration and Capsule
Filtration. Appl. Environ. Microbiol.
67: 1123-1127
[Abstract][Full Text]
Robin,
G., Fraser, D., Orr, N., Sela, T., Slepon, R., Ambar, R., Dagan, R., Le
Blancq, S., Deckelbaum, R. J., Cohen, D. (2001). Cryptosporidium
Infection in Bedouin Infants Assessed by Prospective Evaluation of
Anticryptosporidial Antibodies and Stool Examination. Am J Epidemiol
153: 194-201
[Abstract][Full Text]
Stender,
H., Broomer, A. J., Oliveira, K., Perry-O'Keefe, H., Hyldig-Nielsen, J.
J., Sage, A., Coull, J. (2001). Rapid Detection, Identification, and
Enumeration of Escherichia coli Cells in Municipal Water by
Chemiluminescent In Situ Hybridization. Appl. Environ. Microbiol.
67: 142-147
[Abstract][Full Text]
WYATT, C. R., PERRYMAN, L. E.
(2000). Detection of Mucosally Delivered Antibody to Cryptosporidium parvum p23 in Infected Calves. Ann. N. Y. Acad. Sci.
916: 378-387
[Abstract][Full Text]
Magnuson,
M. L., Owens, J. H., Kelty, C. A. (2000). Characterization of
Cryptosporidium parvum by Matrix-Assisted Laser Desorption
Ionization-Time of Flight Mass Spectrometry. Appl. Environ. Microbiol.
66: 4720-4724
[Abstract][Full Text]
McLauchlin,
J., Amar, C., Pedraza-Díaz, S., Nichols, G. L. (2000). Molecular
Epidemiological Analysis of Cryptosporidium spp. in the United Kingdom:
Results of Genotyping Cryptosporidium spp. in 1,705 Fecal Samples from
Humans and 105 Fecal Samples from Livestock Animals. J. Clin. Microbiol.
38: 3984-3990
[Abstract][Full Text]
Waters,
W. R., Frydman, B., Marton, L. J., Valasinas, A., Reddy, V. K., Harp,
J. A., Wannemuehler, M. J., Yarlett, N. (2000).
[1N,12N]Bis(Ethyl)-cis-6,7-Dehydrospermine: a New Drug for Treatment
and Prevention of Cryptosporidium parvum Infection of Mice Deficient in
T-Cell Receptor Alpha. Antimicrob. Agents Chemother.
44: 2891-2894
[Abstract][Full Text]
SCHWARTZ, J., LEVIN, R.
(2000). Comment. J. Epidemiol. Community Health
54: 729a-730
[Full Text]
MILLS, S. E.
(2000). THE DENTAL UNIT WATERLINE CONTROVERSY: DEFUSING THE MYTHS, DEFINING THE SOLUTIONS. Journal of the American Dental Association
131: 1427-1441
[Abstract][Full Text]
Garcia,
L. S., Shimizu, R. Y., Bernard, C. N. (2000). Detection of Giardia
lamblia, Entamoeba histolytica/Entamoeba dispar, and Cryptosporidium
parvum Antigens in Human Fecal Specimens Using the Triage Parasite
Panel Enzyme Immunoassay. J. Clin. Microbiol.
38: 3337-3340
[Abstract][Full Text]
Haines, A., McMichael, A. J., Epstein, P. R.
(2000). Environment and health: 2. Global climate change and health. CMAJ
163: 729-734
[Full Text]
Kozwich, D., Johansen, K. A., Landau, K., Roehl, C. A., Woronoff, S., Roehl, P. A.
(2000). Development of a Novel, Rapid Integrated Cryptosporidium parvum Detection Assay. Appl. Environ. Microbiol.
66: 2711-2717
[Abstract][Full Text]
Orlandi,
P. A., Lampel, K. A. (2000). Extraction-Free, Filter-Based Template
Preparation for Rapid and Sensitive PCR Detection of Pathogenic
Parasitic Protozoa. J. Clin. Microbiol.
38: 2271-2277
[Abstract][Full Text]
Garcia,
L. S., Shimizu, R. Y. (2000). Detection of Giardia lamblia and
Cryptosporidium parvum Antigens in Human Fecal Specimens Using the
ColorPAC Combination Rapid Solid-Phase Qualitative
Immunochromatographic Assay. J. Clin. Microbiol.
38: 1267-1268
[Abstract][Full Text]
Lalumandier, J. A., Ayers, L. W.
(2000). Fluoride and Bacterial Content of Bottled Water vs Tap Water. Arch Fam Med
9: 246-250
[Abstract][Full Text]
BALLESTER,
F., SUNYER, J. (2000). Drinking water and gastrointestinal disease:
need of better understanding and an improvement in public health
surveillance. J. Epidemiol. Community Health
54: 3-5
[Full Text]
Schwartz, J., Levin, R., Goldstein, R.
(2000). Drinking water turbidity and gastrointestinal illness in the elderly of Philadelphia. J. Epidemiol. Community Health
54: 45-51
[Abstract][Full Text]
Armstrong, G. L., Pinner, R. W.
(1999). Outpatient Visits for Infectious Diseases in the United States, 1980 Through 1996. Arch Intern Med
159: 2531-2536
[Abstract][Full Text]
McLauchlin,
J., Pedraza-Díaz, S., Amar-Hoetzeneder, C., Nichols, G. L. (1999).
Genetic Characterization of Cryptosporidium Strains from 218 Patients
with Diarrhea Diagnosed as Having Sporadic Cryptosporidiosis. J. Clin. Microbiol.
37: 3153-3158
[Abstract][Full Text]
Pillai, D. R., Kain, K. C.
(1999). Immunochromatographic Strip-Based Detection of Entamoeba histolytica-E. dispar and Giardia lamblia Coproantigen. J. Clin. Microbiol.
37: 3017-3019
[Abstract][Full Text]
Kuczynska, E., Shelton, D. R.
(1999). Method for Detection and Enumeration of Cryptosporidium parvum Oocysts in Feces, Manures, and Soils. Appl. Environ. Microbiol.
65: 2820-2826
[Abstract][Full Text]
Nelson, S. P., Lin, P. L., Miller, J., Katz, B. Z., Gonzalez-Crussi, F.
(1999). Cryptosporidia Enterocolitis in an Immunocompetent Infant Treated with Paromomycin. CLIN PEDIATR
38: 367-369
Jenkins,
M. B., Walker, M. J., Bowman, D. D., Anthony, L. C., Ghiorse, W. C.
(1999). Use of a Sentinel System for Field Measurements of
Cryptosporidium parvum Oocyst Inactivation in Soil and Animal Waste. Appl. Environ. Microbiol.
65: 1998-2005
[Abstract][Full Text]
Priest,
J. W., Kwon, J. P., Moss, D. M., Roberts, J. M., Arrowood, M. J.,
Dworkin, M. S., Juranek, D. D., Lammie, P. J. (1999). Detection by
Enzyme Immunoassay of Serum Immunoglobulin G Antibodies That Recognize
Specific Cryptosporidium parvum Antigens. J. Clin. Microbiol.
37: 1385-1392
[Abstract][Full Text]
Doing, K. M., Hamm, J. L., Jellison, J. A., Marquis, J. A., Kingsbury, C.
(1999). False-Positive Results Obtained with the Alexon ProSpecT Cryptosporidium Enzyme Immunoassay. J. Clin. Microbiol.
37: 1582-1583
[Abstract][Full Text]
(1999). False-Positive Laboratory Tests for Cryptosporidium Involving
an Enzyme-Linked Immunosorbent Assay--United States, November
1997-March 1998. JAMA
281: 411-412
[Full Text]
Piper, M. B., Bankier, A. T., Dear, P. H.
(1998). A HAPPY Map of Cryptosporidium parvum. Genome Res.
8: 1299-1307
[Abstract][Full Text]
Spano, F., Putignani, L., Crisanti, A., Sallicandro, P., Morgan, U. M., Le Blancq, S. M., Tchack, L., Tzipori, S., Widmer, G.
(1998). Multilocus Genotypic Analysis of Cryptosporidium parvum Isolates from Different Hosts and Geographical Origins. J. Clin. Microbiol.
36: 3255-3259
[Abstract][Full Text]
Simonsen, L., Conn, L. A., Pinner, R. W., Teutsch, S.
(1998). Trends in Infectious Disease Hospitalizations in the United States, 1980-1994. Arch Intern Med
158: 1923-1928
[Abstract][Full Text]
Seydel,
K. B., Zhang, T., Champion, G. A., Fichtenbaum, C., Swanson, P. E.,
Tzipori, S., Griffiths, J. K., Stanley, S. L. Jr. (1998).
Cryptosporidium parvum Infection of Human Intestinal Xenografts in SCID
Mice Induces Production of Human Tumor Necrosis Factor Alpha and
Interleukin-8. Infect. Immun.
66: 2379-2382
[Abstract][Full Text]
Morgan, U. M., Pallant, L., Dwyer, B. W., Forbes, D. A., Rich, G., Thompson, R. C. A.
(1998). Comparison of PCR and Microscopy for Detection of Cryptosporidium parvum in Human Fecal Specimens: Clinical Trial. J. Clin. Microbiol.
36: 995-998
[Abstract][Full Text]
Pereira, M. d. G. C., Atwill, E. R., Crawford, M. R., Lefebvre, R. B.
(1998). DNA Sequence Similarity between California Isolates of Cryptosporidium parvum. Appl. Environ. Microbiol.
64: 1584-1586
[Abstract][Full Text]
Okhuysen, P. C., Chappell, C. L., Sterling, C. R., Jakubowski, W., DuPont, H. L.
(1998). Susceptibility and Serologic Response of Healthy Adults to Reinfection with Cryptosporidium parvum. Infect. Immun.
66: 441-443
[Abstract][Full Text]
Pedley, S., Howard, G.
(1997). The public health implications of microbiological contamination of groundwater. Quarterly Journal of Engineering Geology and Hydrogeology
30: 179-188
[Abstract]
Darkin-Rattray,
S. J., Gurnett, A. M., Myers, R. W., Dulski, P. M.,
Crumley, T. M., Allocco, J. J., Cannova, C., Meinke,
P. T., Colletti, S. L., Bednarek, M. A., Singh,
S. B., Goetz, M. A., Dombrowski, A. W., Polishook,
J. D., Schmatz, D. M. (1996). Apicidin: A novel antiprotozoal
agent that inhibits parasite histone deacetylase. Proc. Natl. Acad. Sci. USA
93: 13143-13147
[Abstract][Full Text]
Goodgame, R. W.
(1996). Understanding Intestinal Spore-Forming Protozoa: Cryptosporidia, Microsporidia, Isospora, and Cyclospora. ANN INTERN MED
124: 429-441
[Abstract][Full Text]
Vakil, N. B., Schwartz, S. M., Buggy, B. P., Brummitt, C. F., Kherellah, M., Letzer, D. M., Gilson, I. H., Jones, P. G.
(1996). Biliary Cryptosporidiosis in HIV-Infected People after the Waterborne Outbreak of Cryptosporidiosis in Milwaukee. NEJM
334: 19-23
[Abstract][Full Text]
Wilson, M. E
(1995). Infectious diseases: an ecological perspective. BMJ
311: 1681-1684
[Full Text]
DuPont, H. L., Chappell, C. L., Sterling, C. R., Okhuysen, P. C., Rose, J. B., Jakubowski, W.
(1995). The Infectivity of Cryptosporidium parvum in Healthy Volunteers. NEJM
332: 855-859
[Abstract][Full Text]