Sunday, December 11, 2011

Have an ice cold glass of Cryptosporidium hominis

During late March and early April of 1993 Milwaukee, WI experienced the largest waterborne disease outbreak in documented United States history. Over the span of approximately two weeks, it was determined that about 403,000 of an estimated 1.61 million residents in the Milwaukee area became ill. Their symptoms included watery diarrhea, stomach pains and cramping along with a low fever. Additional symptoms that were exhibited included nausea, vomiting, malabsorption of nutrients and also dehydration as a result of the diarrhea. In addition to the significant portion of the population that was infected, at least 104 deaths have been attributed to this outbreak; the majority of which were among elderly and immunocompromised individuals, such as patients with AIDS. Furthermore, once the water supply was identified as the source of infection, Milwaukee was forced to shut down their largest water-treatment plant, leaving hundreds of thousands of inhabitants without running water. So who’s the culprit? What could cause such widespread disease in such a short amount of time? The answer: Cryptosporidium hominis.

This organism is a member of the Phylum Apicomplexa, thus it is an obligate parasite of animals. C. hominis is almost exclusively a parasite of humans, hence its species name. This parasite is able to colonize our gastrointestinal tract, consequently resulting in the gastroenteritis and diarrhea typically found in patients with cryptosporidiosis. Although the first documented case of cryptosporidiosis was reported only 35 years ago, it is now acknowledged that Cryptosporidium is a common cause of diarrhea in immunocompetent people and has almost certainly been a human pathogen for as long as humanity has existed. So how does it work? How are we infected and how does this thing survive?

The parasite normally makes its way into its unsuspecting victim via drinking or recreational water that has been contaminated with oocysts, which are extremely resistant to environmental stresses. These oocysts are excreted in the feces of an already infected individual. Once ingested, sporulated oocysts release motile sporozoites through an opening in the oocyst wall. These sporozoites then attach to intestinal epithelial cells via rhoptries and micronemes found at the apical end of the sporozoite (stage 1 in the accompanying diagram). Once attached to the host cell the sporozoite does not invade it, however the parasite stimulates the fusion of microvilli so that it becomes surrounded by a membrane of host origin.

Life Cycle of Cryptosporidium hominis 
Now called a trophozoite, Cryptosporidium then undergoes a period during which it derives nutrients from the host cell via this adhesion zone (2). Trophozoites then undergo a process called merogeny in which asexual replication occurs creating anywhere from 4-8 merozoites (3). Merozoites are released into the intestinal lumen and can carry out a number of functions. They can infect new intestinal epithelial cells and undergo additional rounds of merogony or undergo a sexual cycle referred to as gametogony (4). During gametogony the merozoites can develop into either microgametocytes or macrogametocytes. The macrogametocytes will mature into macrogametes (5), while the microgametocytes will undergo several rounds of replication to produce many microgametes which are then released into the intestinal lumen (6). Next, a microgamete will fuse with one of the macrogametes (still attached to host epithelial cell) and the resulting zygote undergoes sporogony (7). Sporogony involves two rounds of replication that gives rise to four sporozoites. Fully sporulated oocysts are then shed into the intestinal lumen once sporogony has completed its course (8). These oocysts now can be secreted by the host and taken up by another host, thus completing life cycle of Cryptosporidium (9). It should be noted that each generation can develop and mature in as little as 12 hours.

This short generation time is of great importance to the parasite as it does not appear to make any attempt to evade the host’s immune system. As odd as it may seem, being detected by the host could possibly be this parasite’s means of survival. In fact, if this parasite were not eliminated (shedding of oocysts) from the host in a relatively short amount of time, it could kill its host through dehydration and electrolyte imbalance, preventing oocysts from being released into the environment. So instead of hiding from the host immune system, Cryptosporidium evolved to have a rapid generation time and found a way to benefit from it. Once the immune system musters up enough strength to expel the parasite from the body, it has already formed oocysts ready to be taken up by another unsuspecting victim.

So you think to yourself, “Stay away from contaminated water and I’ll be fine. And besides, I’m not an immunocompromised person so this thing can’t hurt me anyhow.” Well…it might already be too late. A number of surveys have been conducted to gain some insight into the prevalence of the parasite in our environment. In industrialized nations, approximately 0.4% of the population appears to be passing oocysts in their feces at any one time. Also, of the patients admitted into hospitals for diarrhea, 2-3% of them are passing oocysts. However, the sero-prevalence is much higher as 30-35% of the United States population have antibodies to Cryptosporidium. In third world countries, the sero-prevalence is even higher as up to 60-70% of people in these countries have antibodies to this parasite. Because recent studies have suggested these antibodies tend to diminish over time, it is plausible that the majority adult humans have been infected with the Cryptosporidium at least one time during their lives.

In review, C. hominis causes severe bowel distress and can develop into a life-threatening disorder when combined with undernourishment, old-age, and/or a weakened immune system. Additionally, Cryptosporidium is a highly contagious parasite which is almost impossible to eradicate due to its resistance to some of the most commonly used detergents and water disinfectants such as chlorine. As a result, its oocysts frequently circumvent municipal water-purification measures on their way to infect new hosts such as you and me.

By A.S.

1. Clark DP, Sears CL (1996) The pathogenesis of cryptosporidiosis. Parasitology Today
2. Hoxie NJ, Davis JP, Vergeront JM, Nashold RD, Blair KA. Cryptosporidiosis-associated mortality following a massive waterborne outbreak in Milwaukee, Wisconsin. Am J Public Health. 1997 
3. MacKenzie, W.R. et al. 1995. Massive outbreak of waterborne Cryptosporidium infection in Milwaukee, Wisconsin. Recurrence of illness and risk of secondary transmission. Clin. Inf. Dis. 
4. MacKenzie, W.R. et al. 1994. A massive outbreak in Milwaukee of Cryptosporidium infection transmitted through the public water supply. New England Journal of Medicine 

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