Cryptosporidiosis in dogs : Add another agent to the differential diagnosis list, why don't you?

I started my research for this post under the assumption that I was soon going to be buried under a ton of clinical articles and good-practice reviews about Cryptosporidium infections in dogs. I came away bitterly disappointed at the utter lack of clinical pointers.I had fully expected a well defined, pathognomonic diagnostic finding , to have been developed and published under the aegis of one Veterinary Association or the other. Unfortunately, that does not seem to be the case.

Ordinarily, when a case presents with diarrhea, a vet would try to narrow down the possible causes, . A list called the "Differential Diagnosis List" is (mentally) made which is conveniently divided into infectious and non infectious etiological agents that could have caused the clinical sign(s). Agents are eliminated based on clinical evidence and the results of the tests at the clinician's disposal. 'Cryptosporidiosis' is listed among the glorified ranks of Tritrichomonas foetus, Giardia sps, Balantidium coli and metazoans under the broad category of 'Parasites that cause diarrhea' in that definitive guide of lists, called "Differential Diagnosis in Small Animal Medicine"(edited by Gough A.). Listing the disease and not the agent is still a thing of great curiosity to me. On the list that runs six pages, Cryptosporidium has scored a spot. If Cryptosporidium caused diarrhea in dogs frequently, it would earn a firm place on the DD list of  every veterinarian.

However, allow me make a statement that seems to defy all clinical logic, but is firmly within the grasp of commonly understood parasitology knowledge : Cryptosporidium canis, C. parvum and C. meleagridis  (all of which have been found in dogs) do not always seem to produce "clinical" disease in dogs. They are typical parasites, carried along for the journey, which do not really harm the host. They seem to favour featuring in multiple etiology dramas, playing the roles of supporting parasites, neither sufficient nor necessary, over the role of protogonist parasites that direct the ebb and flow of the disease.

To treat this "disease" in dogs with the commonly available coccidiostats would be utterly silly and would cast a clinician in poor light , because the parasite is technically not a Coccidian to begin with. The taxonomy tempests have not been stilled on the displacement of Cryptosporidium from the Coccidian Apicomplexans.

Now, for a brief review of clinical research.
In 2000, the "Dog genotype" was validated by phylogenetic analysis of 18S and HSP70 as the new species, Cryptosporidium canis . (Morgan et al., 2000). Publications have implicated C.canis as the causal agent in both canine and human patients, including a case of a HIV infected human patient who harboured the canine genotype. (Pieniazek et al., 1999) But, how clinically relevant these are, is highly debatable

In the first infection report of Cryptosporidiosis in a week old pup, published in 1983, the authors include this disclaimer, "Cryptosporidia may have played a role in the enteritis seen in this pup, but further studies are needed to establish its pathogenecity". That is, the fact that they saw organisms that resembled Cryptosporidium could have been a happy coincidence, or in strict Pathology terms, "an incidental finding" that masked an insidious underlying cause. (Wilson et al., 1983) It has been established since that "Morphology is not a reliable tool for delineating species within Cryptosporidium" (Fall et al., 2003). Thus, it is impossible to know, which species of Cryptosporidium had infected the pup or if there had been another agent , say CPV that had coinfected it.

In a paper published in the Journal of American Animal Hospital Association in 1999, Willard and Bouley describe the fatal case of an immunocompromised 8 wk old dog that was coinfected with Cryptosporidium and other Coccidia. Which came first - the immunocompromise or the infection - is unknown.

Titilincu et al., in a paper titled "Prevalence of Cryptosporidium Spp. in asymptomatic dogs by ELISA and risk factors associated with infection" , published in Lucrari Stiiniifice Medicina Veterinara Vol XLIII (I) , in 2010 maintain that 53% of the 374 sampled dogs were positive on the ELISA, but were clinically asymptomatic. The positive animals when serotyped, were found to be infected with C.canis.

In a longitudinal study (from birth to 1 year of age) published in Acta Veterinaria Scandinavica in 2007 by Hamnes et al., Cryptosproridium was found by immunofluorescent staining in 44.1% of the 290 sampled animals from Norway. Since they used a direct FITC conjugated MAb against C.parvum, the samples identified were of course exclusively C.parvum. Again, the glaringly obvious point in the study is the complete lack of clinical data to support a clinical infection.

Despite the above mentioned studies, the jury is still out on the importance of Cryptosporidium sps. as a pathogenic agent in dog diarrhea, and we are left to ponder on these questions that will still haunt us:
1. Does Cryptosporidium canis actually cause disease in dogs?
2. What percentage of the cases harbour other enteric pathogens?
3. Do detection methods matter? Is it better to perform a PCR on a clinical sample than to perform a ZN staining on it ?
4. Should all cases that are positive using PCR be prescribed coccidiostats irrespective of clinical status ?
5. Should we add the agent to our DD list just to be safe ?

While some answers are obvious, others require a fair bit of clinical and lab research. To assume that answers will be obtained without both working together is obviously foolish.

References :
Morgan UM, Xiao L, Monis P, et al. Cryptosporidium spp. in domestic dogs: the "dog" genotype. Appl Environ Microbiol 2000;66:2220-2223.

 Pieniazek NJ, Bornay-Llinares FJ, Slemenda SB, et al. New cryptosporidium genotypes in HIV-infected persons. Emerg Infect Dis 1999;5:444-449.

Fall A, Thompson RC, Hobbs RP, et al. Morphology is not a reliable tool for delineating species within Cryptosporidium. J Parasitol 2003;89:399-402.
Wilson RB, Holscher MA, Lyle SJ. Cryptosporidiosis in a pup. J Am Vet Med Assoc1983;183:1005-1006.

A change of direction

The end of the semester is in sight. I had maintained this blog for the MICR756 class and had focused my attention on the 'Public Health Aspects of a complex Apicomplexan disease', viz. Malaria. Over the course of the semester, I found that I liked maintaining a blog and that I actually liked this sort of unofficial scientific writing.

So, from January, the blog will move to a new URL : apicomplexity.blogspot.com and will include topics starring other less known (and according to me, more interesting) apicomplexans such as Cryptosporidium, Isospora etc.

Thank you, all, for your patience. A special thanks to Dr.Nathan Fisher for the idea of a blog .