This is the fourth EIStories, IDNs series of articles about outbreak investigations conducted by CDC EIS Officers.
In early spring of 1993, hospitals and schools in Milwaukee reported staffing issues to the citys Department of Public Health when large numbers of nurses and teachers called out sick. Two city newspapers ran stories on a mystery illness and local officials watched with concern. During a two-week period, an estimated 403,000 people in Milwaukee reported sudden acute watery diarrhea.
It took a team of public health experts including an Epidemic Intelligence Officer embedded in the Wisconsin Department of Public Health to determine the massive outbreak was caused by Cryptosporidium that had contaminated the citys public water supply.
To date, the Milwaukee cryptosporidiosis outbreak is the largest epidemic of waterborne disease reported in U.S. history.
Experts say the lessons learned from this outbreak have helped to prevent another similar outbreak. This is a good example of public health in action for developing long-term national policy. It is important it is to document outbreaks and understand as much as we can about them so appropriate changes can be made, said William R. Mac Kenzie, MD, now a CDC medical epidemiologist who was part of the team of investigators on the case. He was the only EIS officer involved in investigating the cryptosporidiosis outbreak in Milwaukee in 1993.
Infectious Disease News recently spoke with Mac Kenzie about this historic investigation.
Based on information from phone calls received by the health department around April 5, Milwaukee health officials suspected the outbreak was predominant in one part of the city. Because diarrheal illness is typically treated at home, physician reports represented only a small portion of the true outbreak. Surveillance data on diarrhea is not routinely collected from physicians.
William R. Mac Kenzie
Epidemiologists and city public health professionals met with then Milwaukee Mayor John Norquist to determine a plan to mobilize the mystery illness investigation.
Meanwhile, Mac Kenzie and colleagues met with officials from the Milwaukee Water Works. With no background in water treatment facilities, the investigation team had to learn about water treatment issues literally overnight. They learned how Milwaukee treated its water through flocculation, sedimentation, filtering, disinfection with chlorine, and how it was tested for turbidity, which is the amount of cloudiness in water. High turbidity can make harmless water look murky.
Public water in Milwaukee came into the citys northern and southern water treatment plants from two separate pipelines with intakes approximately one mile out in Lake Michigan. After filtering and disinfecting, water from the two treatment plants fed into an interconnected system of water mains so either plant could supply the entire city. The investigation began at the water treatment facilities, but no other sources for the outbreak had yet been ruled out.
Mac Kenzie said the initial reactions of the officials from the Milwaukee Water Works may have slowed the investigation. The Water Works officials were not particularly forthcoming initially, Mac Kenzie said. They were trying to solve problems they were having with unprecedently high turbidity of the treaded water from the southern plant, but they werent straightforward in sharing this information with the team. The Water Works officials looked at turbidity as an aesthetic measure; they wanted the water to look good. The officials were in denial that turbidity could be a measure associated with microbial contamination or that the water could be a source for an outbreak.
When water treatment data was made available, investigators noted spikes in the treated water turbidity from the southern plant beginning March 23 and continuing over the next two weeks. Historically, high turbidity levels occurred occasionally at the two city plants and were not previously associated with the disease. Despite these spikes in turbidity, the treated water produced by the plants met national treatment standards and had undergone more measurements for turbidity than required by law.
After the initial meeting with Water Works officials, Mac Kenzie and other public health officials met while a city press conference was held about the mystery bug.
Jim Kazmierczak, DVM, Wisconsin Division of Health epidemiologist, and Mac Kenzie met to devise how they would proceed in protecting public health and in continuing the investigation.
The Milwaukee City Laboratory director, Steve Gradus, called Mac Kenzie during the meeting to report he had found something interesting in his microscope while examining a patients stool sample. It was Cryptosporidium.
Gradus revealed that in the previous hours, he had received reports regarding seven other patient stool samples sent to labs by physicians in Milwaukee that had Cryptosporidium. In my mind, it was a major clue, Mac Kenzie said.
Mac Kenzie had seen patients with AIDS suffer with cryptosporidiosis and knew that it caused watery diarrhea. He knew cryptosporidiosis is generally spread through water. Based upon reports of extensive absenteeism at schools and hospitals, it was likely that this was a large outbreak suggesting that the source of the outbreak was a broadly distributed product like water. Mac Kenzie knew that Cryptosporidium could not be detected by standard tests of water quality and cannot be killed with chlorine at the concentrations used in routine water treatment.
Incubation for Cryptosporidium is long, ranging from one day to two weeks, and almost always averages seven days for the onset of symptoms.
A pivotal decision
Mac Kenzie immediately met with the mayor and chief epidemiologist as they were coming out of the press conference. He told them Cryptosporidium in the water supply could be the reason for the outbreak and suggested a public notice for all residents in the greater Milwaukee area to boil their water.
This micrograph of a direct fecal smear is stained to detect Cryptosporidium, an intracellular protozoan parasite. Using a modified cold Kinyoun acid-fast staining technique, and under an oil immersion lens, the Cryptosporidium oocysts are red and the yeast cells green.
Source: CDC/Dr. Pearl Ma
The suggestion represented a huge risk, Mac Kenzie explained, because boiling water is not only a hassle, but it could lead to accidental scalding. Also, the investigation had just begun and all possible outbreak sources had not been considered.
There was a lot of hemming and hawing among epidemiologists about a possible warning because we hadnt collected much information yet, Mac Kenzie said.
The mayor asked Jeff B. Davis, MD, an epidemiologist at the Wisconsin Division of Public Health, if he would drink the water knowing the information Mac Kenzie had presented.
Davis said no, and in a pivotal part of the outbreak response, the mayor made a decision.
The mayor said, If you wouldnt drink the water, I dont want the people of Milwaukee to drink it either, Mac Kenzie said. It was very insightful for him to bring up that question and make such a brave decision. I appreciated that kind of leadership.
That night April 7 the mayor appeared on the news and asked Milwaukee residents to boil their drinking water and to throw away ice and ice trays.
The pressure was now intense to get the investigation finished quickly and with scientific rigor that could bear the scrutiny of skeptics. The water boiling order not only affected residents, but a slew of city businesses, including Miller Brewing Company, canning operations, dentists who use water drills and restaurants.
The good news was that Miller Brewing Company cold filters its products and their filters were small enough to remove all Cryptosporidium, Mac Kenzie said.
Canning facilities heated their products to temperatures high enough to kill Cryptosporidium, so another concern was allayed.
A war room for the outbreak was quickly created, complete with a telephone bank, printers, faxes and computers. A questionnaire was created for use by telephone surveyors using computer-generated, random telephone numbers for the greater Milwaukee area.
The first surveys were conducted by public health nurses and STD investigators who were skilled at conducting interviews for the health department. The survey included questions about watery diarrhea frequency and incontinence, a prime symptom of the outbreak. A survey conducted on April 9, 10 and 12, interviewed 482 Milwaukee City residents of which 235 (49%) had watery diarrhea. From April 17 through June 2, 612 households representing 1,662 household members from Milwaukee and the four surrounding counties were contacted, of which 436 (26%) had experienced watery diarrhea during the outbreak.
The citizens were very forthcoming and I appreciate the cooperative and civic nature of how people responded, Mac Kenzie said. They would tell us all about their symptoms and their families.
From the telephone surveys, an association was made with the southern Milwaukee water works district and researchers could gauge the timing of when Cryptosporidium entered the water supply and how many people had thus been affected.
In a novel approach to the epidemiologic investigation, short term visitors to the city were identified and questioned to pinpoint exactly when exposure occurred. By surveying people who were in Milwaukee for only 48 hours visits, researchers were able to determine when Cryptosporidium was present because the visitors were only in town for a fixed amount of time.
We could also show the gestation was exactly that of Cryptosporidium because we had the time they were in Milwaukee and the time they got ill, he said.
Investigators were concerned that they would not be able to show that Cryptosporidium was in the water during the period of exposure suggested by the epidemiologic data. This problem was solved when a southern Milwaukee ice maker called stating that he had two 50 gallon blocks of ice created for ice sculptures on two separate days during the period of interest. When the ice was melted and tested, it was confirmed that Cryptosporidium was in the water.
Plant shuts down
Milwaukee Water Works south plant was shut down on April 9 and the city water mains were flushed. The city was served by the northern plant until June, when the water filters replacement and refurbishing was completed at the southern plant.
Years after the outbreak, new information from laboratory investigators aided in the formulation of a theory regarding the source of Cryptosporidium. The source of Cryptosporidium contamination was human, proven by genotypes. Three rivers run into Milwaukee and come together to flow into a bay made by a small indentation in Lake Michigan. There are three water breaks that protect the bay and thus direct the flow of water out of the bay. The current in Lake Michigan is counterclockwise and sitting at the mouth of the river is a human waste sewage treatment plant for the city.
Heavy rains reported that March may have produced sewage overflows that contaminated the rivers and the bay. Water in the bay was pushed by the counterclockwise currents toward the water intake pipeline for the southern water plant, one mile out in Lake Michigan.
If you drew a line projecting the flow of water from the bay, it would go directly toward the southern plant intake, Mac Kenzie said.
In theory, the Cryptosporidium from overflowing sewers or the sewage treatment plant entered the water supply, which sickened people whose waste went back into the sewers. The sewage system was not working adequately to remove the Cryptosporidium.
Cryptosporidium got into the water supply; people had diarrhea; it went back into the sewer, then into the source water and finally into the drinking water creating a cycle that amplified the size of the outbreak over a two-week period, Mac Kenzie said.
Standards for water treatment facilities were about to be implemented throughout the nation; but even those would not have stopped the Milwaukee outbreak, according to Mac Kenzie.
Officials at other water treatment facilities throughout the country were intensely watching the investigation and every large municipality was doing everything to lower turbidity and improve water quality. Large and medium-sized cities immediately began to do better at filtering their source water, so there was a ripple effect all around, Mac Kenzie said.
While the majority of the population benefited from the investigation, parts of the population still remained at risk. No deaths related to the outbreak were reported in the general population at the time, but researchers who looked at Milwaukee data reported that early HIV-related deaths, estimated at 100, occurred in part because of the cryptosporidiosis outbreak. Researchers found an increase in deaths among people with HIV in the six months following the outbreak, followed by a decrease in expected deaths.
Cryptosporidiosis, like all opportunistic infections in people with low CD4 counts, hastens morbidity and mortality, Mac Kenzie said. It is difficult to say who died with cryptosporidiosis infection as opposed to people who died of cryptosporidiosis, but data show some people with HIV died earlier than they would have had the outbreak not occurred.
A slew of studies followed the initial investigation. Shortly after the outbreak, public pools the most likely conduit for Cryptosporidium transmission throughout the country were reported as sources of outbreaks. This occurred because students and others from Milwaukee who were reporting symptoms traveled to other parts of the country and swam in pools, where chlorine cannot kill the protozoans.
We found outbreaks directly associated with Milwaukee in other parts of the country from people who traveled on spring break and contaminated pools, Mac Kenzie said.
Five years after the outbreak, serum samples of Milwaukee children who were being tested for lead exposure during the time of the outbreak were tested for cryptosporidiosis antibodies. Researchers found that before the outbreak, only about 10% of Milwaukee children had cryptosporidiosis antibodies and soon after the outbreak, cryptosporidiosis antibody rates reached 80%. Children who lived in southern Milwaukee had higher levels of antibody confirming the finding that people more likely to drink water from the southern plant were at an increased risk of infection and suggesting that there was quite a bit of asymptomatic infection.
As do many graduates of the EIS, Mac Kenzie credited the EIS founder, the late Alexander D. Langmuir, MD, for the experts abilities to teach generations of EIS officers to form a hypothesis and conduct a quick, thorough epidemiologic investigation.
Dr. Langmuir was an amazing man. He created the EIS program, and taught scientific rigor and discipline in the conduct of investigations. It is these qualities that brought the CDC international recognition, Mac Kenzie said. – by Kirsten H. Ellis
For more information:
- Mac Kenzie WR, Hoxie NJ, Proctor ME, et al. A massive outbreak of Cryptosporidium infection transmitted through the public water supply.N Engl J Med. 1994;331:161-167.