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The Zoonotic Potential of Cryptosporidium
Cryptosporidium: From Molecules to Disease R.C.A. Thompson, A. Armson and U.M. Ryan (Editors) © 2003 Elsevier B.V. All rights reserved
113
Chapter 14
The Zoonotic Potential of Cryptosporidium R.C. Andrew Thompson
14.1 INTRODUCTION Infectious diseases of animal origin have been the source of more than two-thirds of emerging diseases affecting humans over the past decade (WHO, 1999). Cryptosporidiosis is one of these diseases yet the role of animals in the epidemiology of human cryptosporidial infections remains uncertain. Novel and re-emerging zoonotic diseases are of particular concern because of the difficulties in controlling infections with an often, unknown assemblage of animal reservoirs, and the difficulties of evaluating the public health risk of a spill over of disease transmission to humans. In this context it is important to emphasize that any determination of zoonotic potential is not only purely dependent upon evidence that an infectious agent is shared in nature by humans and other vertebrates, but also on evidence of transmission between the two. In this respect, there is abundant evidence of Cryptosporidium's zoonotic potential. Cryptosporidium parvum or C. parvum-like organisms have been reported from 152 species of mammals (Payer et al., 2000), but it is information on the frequency of zoonotic transmission that is lacking. The first human case of infection with C parvum was described in 1976, and although there was much circumstantial evidence of a link between animal contact and infection in humans (Payer et al., 2000), evidence for zoonotic potential had to await the advent of appropriate molecular tools (Thompson, 2003; Table 14.1). Prior to this, circumstantial evidence of zoonotic exposure was associated with farms and farm animals, riding stables, animal manure and contaminated water (Payer et al., 2000). Early reports drew attention to the association of human infection with exposure to infected livestock, particularly young cattle or sheep (Casemore et al, 1990). The occurrence of secondary spread within households or play-groups following such zoonotic exposure has also been reported (Casemore et al., 1990). Although farm workers and visitors to farms are considered to have contracted cryptosporidiosis by direct contact, indirect zoonotic transmission of Cryptosporidium of livestock origin via water has been considered to be the most important zoonotic source of human infection. This is well illustrated by briefly examining the sequence of events that led to the discovery that humans are susceptible to infection with two different genotypes/species of Cryptosporidium. 14.2 EVIDENCE THAT HUMANS ARE SUSCEPTIBLE TO INFECTION WITH MORE THAN ONE FORM OF CRYPTOSPORIDIUM In the search for sources of waterbome outbreaks of cryptosporidiosis, livestock have often been incriminated as the origin of the contaminating isolate. However, such conclusions were
114 TABLE 14.1 Cryptosporidium in humans: 1976-2002 1976 1982 1982-86 1991 1993 1995-1997 1997 1997 2002
First human case Recognition as an opportunistic pathogen Human cases associated with animals Variation between cattle and human isolates using RFLP Milwaukee waterbome outbreak Molecular characterisation reveals zoonotic potential; C. parvum not a uniform species; evidence of two distinct transmission cycles for C. parvum Molecular epidemiology reveals source of infection in Milwaukee outbreak Differences in infectivity and pathogenesis demonstrated between cattle and human genotypes New species proposed — C. hominis
often only circumstantial, with presumptions being made that run-off from pasture used for cattle, was the predisposing factor. In 1991, RFLP analysis revealed differences between Cryptosporidium of cattle and human origin (Ortega et al., 1991). A series of studies between 1995 and 1997 confirmed this result and more importantly revealed that humans were susceptible to infection with two genotypes of Cryptosporidium', one that also infected livestock, principally cattle, and the other that only infected humans (Awad-el-Kariem et al., 1995; Morgan et al., 1995, 1997). This information was first put into an epidemiological context in 1997 in determining the source of contamination of the notorious Milwaukee outbreak (Peng et al., 1997), and subsequently in a series of outbreaks some of which were shown to be of zoonotic origin (Table 14.2). Interestingly, although cattle, and to a lesser extent sheep, have been repeatedly implicated as sources of waterbome outbreaks, the application of genotyping procedures to the contaminating isolate(s) has often incriminated human effluent as the source. For example, cattle have not been conclusively identified as the source of any waterbome outbreak within the USA, and in Canada, an outbreak in Cranbrook, BC, is the only waterbome outbreak in North America in which oocysts of the bovine genotype have been identified (Fayer et al., 2000). However, there
TABLE 14.2 Outbreaks of cryptosporidiosis'' Outbreak
Transmission
Genotype
1993 Milwaukee 1993 Maine 1996 British 1997 Pennsylvania 1997 UK 1998 Washington 2000 Northern Ireland
Waterbome Foodbome Columbia Animal contact Waterbome Foodbome X2
Human Cattle Waterbome Cattle (Cranbrook); Human (Kelowna) Cattle Human Human Cattle X 1 Human X 1
' Data reviewed in Xiao et al. (2002a).
115 have been outbreaks caused by the bovine genotype in North America linked to direct contact with animals or contaminated food such as the Maine Apple cider outbreak in 1995, the Pennsylvania rural family outbreak in 1997 and the Minnesota Zoo outbreak in 1997 (Sulaiman et al., 1999a,b). 14.3 SOURCES OF HUMAN INFECTION 14.3.1 Livestock Molecular epidemiological tools have thus provided the evidence to support the existence of at least two distinct life cycles of Cryptosporidium involving humans (Fig. 14.1), and a series of other transmission cycles involving what appear to be principally host adapted species and genotypes, although more research is necessary before we can fully understand their significance, if any, to public health (Thompson et al., 2000). As a result of the extensive molecular data that had been obtained on the human and cattle genotypes of C parvum, combined with a growing amount of biological information on these two morphologically identical forms, it has recently been proposed that the human genotype be recognized as a distinct species, Cryptosporidium hominis (Morgan-Ryan et al., 2002).
Fig. 14.1. Transmission of major Cryptosporidium species and genotypes.
116 There has been a steady accumulation of epidemiological data during the last five years in which isolates of Cryptosporidium from human cases have been genotyped (Table 14.3). This has revealed some interesting differences between the situation in Australia and North America, where most cases appear to be of human origin, and in Europe where zoonotic sources of infection appear to be more common. These can only be general observations at present and more focused molecular epidemiological studies in defined endemic foci are required to gain a better understanding of transmission. For example, the study by Read et al. (2001) in day care centres found that all infected children harbored the human genotype of C parvum (i.e. C hominis), a result to be expected in an environment favoring direct, person-to-person transmission. In contrast, although only a few cases were examined, the study by Fretz et al. (2003) in Switzerland (Table 14.3), where there is a reliance on surface waters and where there are large numbers of cattle in close association with water sources and people, waterbome zoonotic transmission would not be unexpected. It is interesting therefore, that in the United Kingdom, where zoonotic transmission has been considered to be the major route of cryptosporidial infection in humans, regulations imposed during the recent outbreak of foot and mouth diseases are thought to be the reason for the recent decline in cases of cryptosporidiosis in humans. These regulations removed access to the countryside thus preventing humans from coming into contact with farms, wild animals and their excrement (Hunter et al., 2003). 14.3.2 Companion Animals Apart from livestock and their clear role as reservoirs of zoonotic cryptosporidial infection, companion animals have long been considered potential sources of human infection. However, despite the frequency with which pets are present in households of infected patients, rarely have they been implicated as a source of infection (Casemore et al., 1990). Until recently, surveys of dogs and cats in most developed countries revealed Cryptosporidium to be prevalent but no information was provided on the genotypes present. Similarly, a recent survey of equine cryptosporidiosis in Poland demonstrated that 9.4% of 43 horses were infected, and although raising the possibility of zoonotic transmission, the genotype(s) affecting the horses was not determined (Majewska et al., 1999). Recent studies in which oocysts recovered from dogs and cats have been genotyped have shown that they are most commonly infected with what appear to be predominantly host-adapted species; TABLE 14.3 C parvum in humans n Morgan et al. (1998) Sulaiman et al. (1998) Ong et al. (2002) Xiao et al. (2002a,b) Read et al. (2002) Pedraza-Diaz et al. (2001) Lowery et al. (2001) Fretz et al. (2003)
36 50 150 127 39 2057 39
Location Western Australia USA Canada Peru Western Australia UK Northern Ireland Switzerland
Cattle genotype 17% 18% 19% 12.6% 0% 60% 87.2% 100%
Human genotype 83% 83% 72% 71.7% 100% 38% 12.8% 0%
117
Cryptosporidium canis and Cryptosporidium felis (Abe et al., 2002; Thompson, 2003). The study by Abe et al. (2002) in Osaka, Japan is an excellent illustration of how molecular epidemiological techniques can provide far more meaningful data to what otherwise would have been a much less valuable survey. These authors examined samples from 140 stray adult dogs captured in the city of Osaka and of the 13 positive all were shown by PCR to harbour Cryptosporidium canis. Thus, dogs and cats and possibly other companion animals may not be important zoonotic reservoirs of Cryptosporidium infection. However, molecular characterization of oocysts recovered from infected animals in many more endemic areas is required before this assumption can be verified. It should also be emphasized that companion animals, particularly dogs and cats, may act as mechanical vectors for Cryptosporidium, with oocysts they have ingested passing through the gut intact and acting as a source of infection either through environmental contamination or directly. This has been demonstrated with other parasites such as Ascaris lumbricoides (Traub et al., 2002). The frequency that this may occur with Cryptosporidium is not clear, but the potential was demonstrated recently with the recovery of both Cryptosporidium baileyi and Cryptosporidium muris oocysts from cat feces (McGlade et al., 2003). 14.4 HOST SUSCEPTIBILITY AND SPECIFICITY Those most at risk of contracting cryptosporidiosis are the very young, the elderly and in particular, immunocompromised individuals. It is now well documented that any impairment of immunity, primarily T-cell mediated, will adversely affect an infected individual's ability to recover from an infection with Cryptosporidium. It is also clear, that if the immune system is compromised, host susceptibility is lowered with respect to the range of species and genotypes capable of initiating an infection. Thus immunodeficient individuals, particularly those with AIDS, have been shown to be susceptible to infection with C canis, C felis, C. muris and Cryptosporidium meleagridis, as well as C hominis and C. parvum. Although, immunity must play an important role in determining host specificity, recent surveys have recovered C meleagridis, C felis and C canis from apparently immunocompetent humans (Pedraza-Diaz et al., 2001; Xiao et al., 2001). It is uncertain whether nutritional factors or age contributed to the establishment of infection with these species in humans. It is also possible that the isolates recovered from these patients may have been variants, genetically distinct from isolates of those species normally found in non-human hosts. It has also been suggested that C meleagridis was originally a parasite of mammals that has subsequently established in birds (Xiao et al., 2002b). 14.5 CONCLUSIONS Cryptosporidium is clearly a zoonotic parasite. Recent molecular epidemiological studies have confirmed the zoonotic potential of C parvum, and in particular, the role of livestock as sources of infection with this species in humans. Data are still lacking on the frequency with which zoonotic transmission occurs. However, as molecular genotyping tools are increasingly applied to oocysts collected during routine surveillance, studies in localized endemic foci of transmission and outbreak situations, the resulting data will not only provide information on how frequently zoonotic transmission occurs, but also under what epidemiological circumstances.
118
REFERENCES Abe, N., Sawano, Y., Yamada, K., Kimata, I. and Iseki, M., 2002. Cryptosporidium infection in dogs in Osaka, Japan. Vet. Parasitol., 108: 185-193. Awad-el-Kariem, F.M., Robinson, H.A., Dyson, D.A., Evans, D., Wright, S., Fox, M.T. and McDonald, V., 1995. Differentiation between human and animal strains of Cryptosporidium parvum using isoenzyme typing. Parasitology, 110: 129-132. Casemore, D.P., 1990. Epidemiological aspects of human cryptosporidiosis. Epidemiol. Infect., 104: 1. Payer, R., Morgan, U. and Upton, S.J., 2000. Epidemiology of Cryptosporidium: transmission, detection and identification. Int. J. Parasitol., 30: 1305-1322. Fretz, R., Svoboda, P., Morgan, U.M., Thompson, R.C.A., Tanner, M. and Baumgartner, A., 2003. Genotyping of Cryptosporidium spp. isolated from human stool samples in Switzerland. Epidemiol. Infn., in press. Hunter, P.R., Chalmers, R.M., Syed, Q., Hughes, L.S., Woodhouse, S. and Swift, L., 2003. Foot and mouth disease and cryptosporidiosis: possible interaction between two emerging infectious diseases. Emer. Inf. Dis., 9: 109-112. Lowery, C.J., Millar, B.C., Moore, I.E., Xu, J., Xiao, L., Rooner, P.J., Crothers, L. and Dooley, J.S., 2001. Molecular genotyping of human cryptosporidiosis in Northern Ireland: epidemiological aspects and review. Ir. J. Med. Sci., 170: 246-250. Majewska, A.C., Werner, A., Sulima, P. and Luty, T., 1999. Survey on equine cryptosporidiosis in Poland and the possibility of zoonotic transmission. Ann. Agric. Environ. Med., 6: 161-165. McGlade, T.R., Robertson, I.D., Elliot, A.D. and Thompson, R.C.A., 2003. High prevalence of Giardia detected in cats by PCR. Vet. Parasitol., 110: 197-205. Morgan, U.M., Constantine, C.C, O'Donoghue, P., O'Brien, P.A. and Thompson, R.C.A., 1995. RAPD (random amplified polymorphic DNA) analysis of Cryptosporidium isolates. Am. J. Trop. Med. Hyg., 52: 559-564. Morgan, U.M., Constantine, C.C, Forbes, D.A. and Thompson, R.C.A., 1997. Differentiation between human and animal isolates of Cryptosporidium parvum using rDNA sequencing and direct PCR analysis. J. Parasitol., 83: 825-830. Morgan, U.M., Pallant, L., Dwyer, B., Forbes, D.A., Rich, G. and Thompson, R.C.A., 1998. Comparison of PCR versus microscopy for the detection of Cryptosporidium — A clinical trial. J. Clin. Microbiol., 36: 995-998. Morgan-Ryan, U.M., Fall, A., Ward, L.A., Hijjawi, N., Sulaiman, I., Payer, R., Thompson, R.C.A., Olson, M., Lai, A. and Xiao, L., 2002. Cryptosporidium hominis n. sp. (Apicomplexa: Cryptosporidiidae) from Humans, Homo sapiens. J. Euk. Microbiol., 49: 433-440. Ong, C.S.L., Eisler, D.L., Alikhani, A., Fung, V.W.K., Tomblin, J., Bowie, W.R. and Isaac-Renton, J.L., 2002. Novel Cryptosporidium genotypes in sporadic cryptosporidiosis cases: fist report of human infections with a cervine genotype. Emerg. Inf. Dis., 8: 263-268. Ortega, Y.R., Sheehy, R.R., Cama, V.A., Oishi, K.K. and Steriing, C.R., 1991. Restriction fragment length polymorphism analysis of Cryptosporidium parvum isolates of bovine and human origin. J. ProtozooL, 38: 40-41. Pedraza-Diaz, S., Amar, C , Nichols, G.L. and McLaughlin, J., 2001. Nested polymerase chain reaction for amplification of the Cryptosporidium oocyst wall protein gene. Emer. Inf. Dis., 7: 49-56. Peng, M.M., Xiao, L., Freeman, A.R., Arrowood, M.J., Escalante, A.A., Weltman, A.C., Ong, C.S.L., MacKenzie, W.R., Lai, A. A. and Beard, C.B., 1997. Genetic polymorphism among Cryptosporidium parvum isolates: evidence of two distinct human transmission cycles. Emer. Inf. Dis., 34: 567-573. Read, C , Walters, J., Robertson, I.D. and Thompson, R.C.A., 2001. Correlation between genotypes of Giardia duodenalis and diarrhoea. Int. J. Parasitol., 32: 229-231. Sulaiman, I.M., Xiao, L., Yang, C , Escalante, L., Moore, A., Beard, C.B., Arrowood, M.J. and Lai, A.A., 1998. Differentiating human from animal isolates of Cryptosporidium parvum. Emerg. Inf. Dis., 4: 681-685. Sulaiman, I.M., Xiao, L. and Lai, A.A., 1999a. Evaluation of Cryptosporidium parvum genotyping techniques. Appl. Environ. Microbiol., 65: 4431-4435. Sulaiman, I., Lai, A., Fyfe, M., King, A., Bowie, W.R. and Isaac-Renton, J.L., 1999b. Molecular epidemiology of cryptosporidiosis outbreaks and transmission in British Columbia, Canada. Am. J. Trop. Med. Hyg., 61: 63-69. Thompson, R.C.A., 2003. Molecular epidemiology of Giardia and Cryptosporidium infections. J. Parasitol., in press. Thompson, R.C.A., Morgan, U.M., Hopkins, R.M. and Pallant, L.J., 2000. Enteric protozoan infections. In: R.C.A. Thompson (Ed.), The Molecular Epidemiology of Infectious Diseases. Arnold, pp. 194-209.
119 Traub, R.J., Robertson, I.D., Irwin, P., Mencke, N. and Thompson, R.C.A., 2002. The role of dogs in transmission of gastrointestinal parasites in a remote tea-growing community in northeast India. Am. J. Trop. Med. Hyg., 67: 539-545. WHO, 1999. Report on infectious diseases: removing obstacles to healthy development. World Health Organization, Geneva. Xiao, L., Bern, C , Limor, J., Sulaiman, I., Roberts, J., Checkley, W., Cabrera, L, Oilman, R.H. and Lai, A.A., 2001. Identification of 5 types of Cryptosporidium parasites in children in Lima, Peru. J. Inf. Dis., 183: 492-497. Xiao, L., Bern, C.J., Sulaiman, I.M. and Lai, A.A., 2002a. Molecular epidemiology of human cryptosporidiosis. In: R.C.A. Thompson, A. Armson and U.M. Morgan-Ryan (Eds.), Cryptosporidium from molecules to disease. Elsevier, Amsterdam, in press. Xiao, L., Bern, C.J., Arrowood, M., Sulaiman, I., Zhou, L., Kawai, V., Vivar, A., Lai, A.A. and Oilman, R.H., 2002b. Identification of the Cryptosporidium pig genotype in a human patient. J. Inf. Dis., 185: 1846-1848.
113
Chapter 14
The Zoonotic Potential of Cryptosporidium R.C. Andrew Thompson
14.1 INTRODUCTION Infectious diseases of animal origin have been the source of more than two-thirds of emerging diseases affecting humans over the past decade (WHO, 1999). Cryptosporidiosis is one of these diseases yet the role of animals in the epidemiology of human cryptosporidial infections remains uncertain. Novel and re-emerging zoonotic diseases are of particular concern because of the difficulties in controlling infections with an often, unknown assemblage of animal reservoirs, and the difficulties of evaluating the public health risk of a spill over of disease transmission to humans. In this context it is important to emphasize that any determination of zoonotic potential is not only purely dependent upon evidence that an infectious agent is shared in nature by humans and other vertebrates, but also on evidence of transmission between the two. In this respect, there is abundant evidence of Cryptosporidium's zoonotic potential. Cryptosporidium parvum or C. parvum-like organisms have been reported from 152 species of mammals (Payer et al., 2000), but it is information on the frequency of zoonotic transmission that is lacking. The first human case of infection with C parvum was described in 1976, and although there was much circumstantial evidence of a link between animal contact and infection in humans (Payer et al., 2000), evidence for zoonotic potential had to await the advent of appropriate molecular tools (Thompson, 2003; Table 14.1). Prior to this, circumstantial evidence of zoonotic exposure was associated with farms and farm animals, riding stables, animal manure and contaminated water (Payer et al., 2000). Early reports drew attention to the association of human infection with exposure to infected livestock, particularly young cattle or sheep (Casemore et al, 1990). The occurrence of secondary spread within households or play-groups following such zoonotic exposure has also been reported (Casemore et al., 1990). Although farm workers and visitors to farms are considered to have contracted cryptosporidiosis by direct contact, indirect zoonotic transmission of Cryptosporidium of livestock origin via water has been considered to be the most important zoonotic source of human infection. This is well illustrated by briefly examining the sequence of events that led to the discovery that humans are susceptible to infection with two different genotypes/species of Cryptosporidium. 14.2 EVIDENCE THAT HUMANS ARE SUSCEPTIBLE TO INFECTION WITH MORE THAN ONE FORM OF CRYPTOSPORIDIUM In the search for sources of waterbome outbreaks of cryptosporidiosis, livestock have often been incriminated as the origin of the contaminating isolate. However, such conclusions were
114 TABLE 14.1 Cryptosporidium in humans: 1976-2002 1976 1982 1982-86 1991 1993 1995-1997 1997 1997 2002
First human case Recognition as an opportunistic pathogen Human cases associated with animals Variation between cattle and human isolates using RFLP Milwaukee waterbome outbreak Molecular characterisation reveals zoonotic potential; C. parvum not a uniform species; evidence of two distinct transmission cycles for C. parvum Molecular epidemiology reveals source of infection in Milwaukee outbreak Differences in infectivity and pathogenesis demonstrated between cattle and human genotypes New species proposed — C. hominis
often only circumstantial, with presumptions being made that run-off from pasture used for cattle, was the predisposing factor. In 1991, RFLP analysis revealed differences between Cryptosporidium of cattle and human origin (Ortega et al., 1991). A series of studies between 1995 and 1997 confirmed this result and more importantly revealed that humans were susceptible to infection with two genotypes of Cryptosporidium', one that also infected livestock, principally cattle, and the other that only infected humans (Awad-el-Kariem et al., 1995; Morgan et al., 1995, 1997). This information was first put into an epidemiological context in 1997 in determining the source of contamination of the notorious Milwaukee outbreak (Peng et al., 1997), and subsequently in a series of outbreaks some of which were shown to be of zoonotic origin (Table 14.2). Interestingly, although cattle, and to a lesser extent sheep, have been repeatedly implicated as sources of waterbome outbreaks, the application of genotyping procedures to the contaminating isolate(s) has often incriminated human effluent as the source. For example, cattle have not been conclusively identified as the source of any waterbome outbreak within the USA, and in Canada, an outbreak in Cranbrook, BC, is the only waterbome outbreak in North America in which oocysts of the bovine genotype have been identified (Fayer et al., 2000). However, there
TABLE 14.2 Outbreaks of cryptosporidiosis'' Outbreak
Transmission
Genotype
1993 Milwaukee 1993 Maine 1996 British 1997 Pennsylvania 1997 UK 1998 Washington 2000 Northern Ireland
Waterbome Foodbome Columbia Animal contact Waterbome Foodbome X2
Human Cattle Waterbome Cattle (Cranbrook); Human (Kelowna) Cattle Human Human Cattle X 1 Human X 1
' Data reviewed in Xiao et al. (2002a).
115 have been outbreaks caused by the bovine genotype in North America linked to direct contact with animals or contaminated food such as the Maine Apple cider outbreak in 1995, the Pennsylvania rural family outbreak in 1997 and the Minnesota Zoo outbreak in 1997 (Sulaiman et al., 1999a,b). 14.3 SOURCES OF HUMAN INFECTION 14.3.1 Livestock Molecular epidemiological tools have thus provided the evidence to support the existence of at least two distinct life cycles of Cryptosporidium involving humans (Fig. 14.1), and a series of other transmission cycles involving what appear to be principally host adapted species and genotypes, although more research is necessary before we can fully understand their significance, if any, to public health (Thompson et al., 2000). As a result of the extensive molecular data that had been obtained on the human and cattle genotypes of C parvum, combined with a growing amount of biological information on these two morphologically identical forms, it has recently been proposed that the human genotype be recognized as a distinct species, Cryptosporidium hominis (Morgan-Ryan et al., 2002).
Fig. 14.1. Transmission of major Cryptosporidium species and genotypes.
116 There has been a steady accumulation of epidemiological data during the last five years in which isolates of Cryptosporidium from human cases have been genotyped (Table 14.3). This has revealed some interesting differences between the situation in Australia and North America, where most cases appear to be of human origin, and in Europe where zoonotic sources of infection appear to be more common. These can only be general observations at present and more focused molecular epidemiological studies in defined endemic foci are required to gain a better understanding of transmission. For example, the study by Read et al. (2001) in day care centres found that all infected children harbored the human genotype of C parvum (i.e. C hominis), a result to be expected in an environment favoring direct, person-to-person transmission. In contrast, although only a few cases were examined, the study by Fretz et al. (2003) in Switzerland (Table 14.3), where there is a reliance on surface waters and where there are large numbers of cattle in close association with water sources and people, waterbome zoonotic transmission would not be unexpected. It is interesting therefore, that in the United Kingdom, where zoonotic transmission has been considered to be the major route of cryptosporidial infection in humans, regulations imposed during the recent outbreak of foot and mouth diseases are thought to be the reason for the recent decline in cases of cryptosporidiosis in humans. These regulations removed access to the countryside thus preventing humans from coming into contact with farms, wild animals and their excrement (Hunter et al., 2003). 14.3.2 Companion Animals Apart from livestock and their clear role as reservoirs of zoonotic cryptosporidial infection, companion animals have long been considered potential sources of human infection. However, despite the frequency with which pets are present in households of infected patients, rarely have they been implicated as a source of infection (Casemore et al., 1990). Until recently, surveys of dogs and cats in most developed countries revealed Cryptosporidium to be prevalent but no information was provided on the genotypes present. Similarly, a recent survey of equine cryptosporidiosis in Poland demonstrated that 9.4% of 43 horses were infected, and although raising the possibility of zoonotic transmission, the genotype(s) affecting the horses was not determined (Majewska et al., 1999). Recent studies in which oocysts recovered from dogs and cats have been genotyped have shown that they are most commonly infected with what appear to be predominantly host-adapted species; TABLE 14.3 C parvum in humans n Morgan et al. (1998) Sulaiman et al. (1998) Ong et al. (2002) Xiao et al. (2002a,b) Read et al. (2002) Pedraza-Diaz et al. (2001) Lowery et al. (2001) Fretz et al. (2003)
36 50 150 127 39 2057 39
Location Western Australia USA Canada Peru Western Australia UK Northern Ireland Switzerland
Cattle genotype 17% 18% 19% 12.6% 0% 60% 87.2% 100%
Human genotype 83% 83% 72% 71.7% 100% 38% 12.8% 0%
117
Cryptosporidium canis and Cryptosporidium felis (Abe et al., 2002; Thompson, 2003). The study by Abe et al. (2002) in Osaka, Japan is an excellent illustration of how molecular epidemiological techniques can provide far more meaningful data to what otherwise would have been a much less valuable survey. These authors examined samples from 140 stray adult dogs captured in the city of Osaka and of the 13 positive all were shown by PCR to harbour Cryptosporidium canis. Thus, dogs and cats and possibly other companion animals may not be important zoonotic reservoirs of Cryptosporidium infection. However, molecular characterization of oocysts recovered from infected animals in many more endemic areas is required before this assumption can be verified. It should also be emphasized that companion animals, particularly dogs and cats, may act as mechanical vectors for Cryptosporidium, with oocysts they have ingested passing through the gut intact and acting as a source of infection either through environmental contamination or directly. This has been demonstrated with other parasites such as Ascaris lumbricoides (Traub et al., 2002). The frequency that this may occur with Cryptosporidium is not clear, but the potential was demonstrated recently with the recovery of both Cryptosporidium baileyi and Cryptosporidium muris oocysts from cat feces (McGlade et al., 2003). 14.4 HOST SUSCEPTIBILITY AND SPECIFICITY Those most at risk of contracting cryptosporidiosis are the very young, the elderly and in particular, immunocompromised individuals. It is now well documented that any impairment of immunity, primarily T-cell mediated, will adversely affect an infected individual's ability to recover from an infection with Cryptosporidium. It is also clear, that if the immune system is compromised, host susceptibility is lowered with respect to the range of species and genotypes capable of initiating an infection. Thus immunodeficient individuals, particularly those with AIDS, have been shown to be susceptible to infection with C canis, C felis, C. muris and Cryptosporidium meleagridis, as well as C hominis and C. parvum. Although, immunity must play an important role in determining host specificity, recent surveys have recovered C meleagridis, C felis and C canis from apparently immunocompetent humans (Pedraza-Diaz et al., 2001; Xiao et al., 2001). It is uncertain whether nutritional factors or age contributed to the establishment of infection with these species in humans. It is also possible that the isolates recovered from these patients may have been variants, genetically distinct from isolates of those species normally found in non-human hosts. It has also been suggested that C meleagridis was originally a parasite of mammals that has subsequently established in birds (Xiao et al., 2002b). 14.5 CONCLUSIONS Cryptosporidium is clearly a zoonotic parasite. Recent molecular epidemiological studies have confirmed the zoonotic potential of C parvum, and in particular, the role of livestock as sources of infection with this species in humans. Data are still lacking on the frequency with which zoonotic transmission occurs. However, as molecular genotyping tools are increasingly applied to oocysts collected during routine surveillance, studies in localized endemic foci of transmission and outbreak situations, the resulting data will not only provide information on how frequently zoonotic transmission occurs, but also under what epidemiological circumstances.
118
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