Cryptosporidium parvum: Household Transmission

Diarrheal disease, particularly in children residing in developing countries, is still a major cause of illness and death. Estimates for the late 1970s and early 1980s [1] suggested that in Asia, Africa, and Latin America alone more than 5 billion episodes of diarrheal illness and 5 to 10 million diarrhea-associated deaths occurred annually. More recent estimates [2] from the World Health Organization provide additional perspective on the worldwide problem of diarrheal illness in children. The World Health Organization estimated that in 1991, 4.3 million deaths occurred in children from acute respiratory infections, 3.5 million from diarrheal diseases, approximately 1 million from malaria, and 0.88 million from measles. Data from more than 100 geographically based surveys clearly show that cryptosporidia are one of the major enteropathogens causing diarrheal illness worldwide and that this enteropathogen contributes substantially to illness and death among children, especially malnourished children in developing countries [3]. In this issue of Annals, Newman and colleagues [4] present data that enlarge our understanding of the person-to-person transmission and the household epidemiology of C. parvum infections. The authors did a thorough and difficult study of the transmission of cryptosporidial infections in households with identified cases of cryptosporidiosisall in the setting of an urban slum in Fortaleza, Brazil. Clarke [5], in 1895, may have been the first to observe a species of Cryptosporidium that he described as swarm spores lying upon the gastric epithelium of mice. In retrospect, these small organisms were probably the motile merozoites of Cryptosporidium muris, the species named and described approximately 12 years later by the well-known American parasitologist, E. E. Tyzzer [6]. Five years later, in 1912, Tyzzer [7] described much of the morphologic characteristics and life cycle of a second species, C. parvum, found in the small intestine of laboratory mice. During the ensuing 70 years, this small coccidian parasite, one with close taxonomic affinities to Toxoplasma gondii, was virtually ignored. Even the first two cases of human cryptosporidiosis, reported in 1976 [8, 9], were overlooked by the biomedical communityafter all, the concept of cryptosporidia was that of a rare, opportunistic pathogen outside its normal host range. But beginning in 1982, our concept of these protozoan parasites changed. Investigators now believe that at least one species of Cryptosporidium is an important, widespread cause of diarrheal illness in humans and some domesticated animals [10]. We now know that C. parvum is a primary enteropathogen that may cause a short-term (3- to 20-day) diarrheal illness in immunocompetent persons that usually resolves spontaneously and may cause a prolonged, life-threatening, cholera-like illness in immune-deficient patients, especially those with the acquired immunodeficiency syndrome (AIDS). Data from more than 100 geographically based surveys indicate that the mean prevalence rate for Cryptosporidium infection is between 1% and 3% in Europe and North America and is considerably higher in underdeveloped continents, ranging from 5% in Asia to approximately 10% in Africa [3]. Newman and colleagues [4] found a high transmission rate of Cryptosporidium infections in households with identified persons who had cryptosporidiosis in an urban slum in Fortaleza, Brazil. Of the 223 members of 31 households with a child younger than 3 years of age who was positive for Cryptosporidium oocysts in the stool (household index case), 219 (98%) were enrolled in the study. During the 6-week surveillance period, 71% of the participants submitted three stool specimens for detection of oocysts by acid-fast staining, and 77% submitted serum specimens for the detection of Cryptosporidium-specific antibodies (IgM and IgG). One remarkable feature was the high rate of transmission of C. parvum infection within the study group. Using the stringent criteria of at least one Cryptosporidium-positive stool sample or seroconversion, 18 (51%) of the 31 households had at least one secondary case of cryptosporidiosis, and 19% of family contacts had documented C. parvum infection during the 6-week surveillance period. The authors indicated [4] that this rate of transmission is similar to that documented for other highly transmissible enteric pathogens that are transmitted by the fecal-oral route, such as Shigella species and rotavirus. The high rate of transmission of C. parvum infection within the study group was also confirmed by the finding that 94.6% of the participants were seropositiveby far the highest seropositivity rates documented for any study. The endemicity of C. parvum in the study group may help explain some of the clinical findings. Twenty-nine of the 31 (94%) index cases (whose mean age was 11 months) had diarrhea when Cryptosporidium infection was documented by stool examination. Their diarrheal illness was lengthy (mean duration, 13 days; range, 1 to 84 days), and 13 (45%) met the World Health Organization criteria for persistent diarrhea. In contrast, only 8 of the 30 (27%) secondary cases confirmed by stool examination or seroconversion had documented diarrhea. Although the age range of symptomatic and asymptomatic persons from the secondary cases was similar, the median age of those with diarrhea was younger (29 months compared with 7 years) and a higher percentage were children 5 years of age or younger. These data confirm observations by others [3, 11] that C. parvum infections are more prevalent and more severe in younger children, especially in highly endemic regions. These data also support the concept that symptomatic infections result in the development of protective immunity; this immunity may not completely block infection on re-exposure to oocysts, but it may protect the host against clinical illness [12]. Some of my observations during the early 1980s may also be relevant to the clinical observations reported by Newman and colleagues [4]. A student contracted three, documented (by stool examination) C. parvum infections during a 12-month period when working with heavily infected calves. The first infection resulted in severe, watery diarrhea lasting approximately 9 days [13], whereas the second and third infections were associated with only minor gastrointestinal upset and soft stools for 2 to 3 days; these occurred approximately 4 and 10 months after the first documented infection. This student probably had multiple exposures during the 12 months; thus, the 4- and 6-month asymptomatic periods before the second and third infections may have been because of protective immunity, and the onset of mild cryptosporidiosis may have occurred because of the waning of such immunity. A similar scenario may be occurring in communities such as the one studied in Fortaleza, Brazil. In communities where C. parvum is highly endemic, the first and perhaps the second exposure result in severe diarrheal illness in young children; subsequent oocyst challenge over time probably results in no infection, asymptomatic infection, or mild cryptosporidiosis, depending on the level of protective immunity at the time of exposure. In communities where C. parvum is relatively rare, diarrheal illness because of secondary transmission is probably common [4]. Such speculation is supported by reports from the United States of high attack rates of cryptosporidial diarrhea that are associated with common-source exposure in daycare centers [3, 14, 15] and with several waterborne outbreaks [3, 16, 17]. The highly transmissible nature of Cryptosporidium shown by Newman and colleagues underscores the risk for acquiring cryptosporidial diarrhea in highly endemic areas, especially by travelers from regions where the rate of exposure to the parasite is lower [3, 18]. Another important concern stems from the spread of AIDS in communities such as the one in Fortaleza, Brazil, where diarrhea remains a serious threat to the health of young children. Patients with late-stage AIDS (regardless of age) are highly susceptible to cryptosporidiosis, and after exposure, most develop prolonged, severe life-threatening diarrhea [3, 11]. To date, no documented effective treatment exists for cryptosporidiosis in immunocompromised persons.