Bill & Melinda Gates Foundation

Shedding Light on Cryptosporidium, an Under-Addressed Killer

March 17, 2014

Cryptosporidium (Crypto) is an intracellular protozoan parasite that causes mild to severe infection known as cryptosporidiosis (crypto). Those infected with Crypto can develop persistent diarrhea and face risk of death from dehydration.  Additionally, Crypto infection has been shown to cause longer-term effects such as stunting and cognitive impairment, though the severity and extent of these outcomes requires further study.  There is also a correlation between crypto and malnourishment in children. Malnutrition may predispose children to infection, but the symptoms of Crypto infection may also impede nutrient absorption and thereby cause malnutrition, leading to a longer lasting, vicious cycle of reinfection.

For many years, Crypto had been thought of primarily as a disease that affected immunocompromised individuals, particularly those with HIV/AIDS.  While it was believed to be a diarrheal disease that impacted children in the developing world, Crypto was not seen as a primary driver of morbidity and mortality in this population.

Publication of the Global Enteric Multi-Center Study (GEMS) in 2013 told a different story about Crypto, one that showed Crypto as a key pathogen in diarrheal disease, even among otherwise healthy children.  GEMS evaluated the burden of Crypto, as well as other enteric diseases, among more than 20,000 children across seven sites in sub-Saharan Africa and South Asia. The burden of disease was found to be much higher than previously anticipated: Crypto was the second leading cause of moderate-to-severe diarrhea in infants (0-11 months) and the third most common cause in toddlers (12-23 months).  According to the results of GEMS, Crypto had a higher disease burden in these populations than Cholera and Norovirus, which have previously received more research attention. Crypto was also found to be associated with a more than twofold increase in the risk of death in toddlers (12-23 months) hospitalized with diarrhea.

Uphill Battle: Challenges in Addressing the Cryptosporidium Burden

All species of Crypto are highly resilient organisms with a variety of modes of transmission, making the disease difficult to control throughout the entire infection cycle. In particular, Crypto can be transmitted through water, food, soil, touch and air. Crypto is not killed by chlorination and can remain infectious in the environment for as long as 6 months, making it difficult to eradicate in these transmission pathways.  Even in the face of improving sanitation in the developing world, Crypto may continue to persist given the pathogen’s heartiness. 

Another challenge comes from the fact that, prior to the publication of GEMS, Crypto received less international attention than other diarrheal diseases. Research into the parasite was mostly in smaller, more local studies and industry funding of Crypto was limited. As a result, there are few commercially available Crypto products. One treatment option and a number of diagnostic tools are available, but not widely used. No vaccine currently exists, and the timeline to develop one is expected to be long. In most of the developing world, Crypto is treated only through rehydration, if it is treated at all.

This lack of attention also means that vaccine and treatment research and development are in early stages.  One of the reasons that this work is still nascent is due to the lack of enabling tools to support development of treatments and vaccines. For example, researchers currently have difficulty replicating the Crypto parasite in a lab, and there is no small animal model to enable testing that is believed to approximate human response.  These gaps make it challenging to both identify and test vaccine or treatment options.  In addition, there are key factors about Crypto and how it behaves within other organisms that require further study.  The host’s immune response to infection by the parasite is not well understood, and the Crypto genome is not fully annotated, which leaves critical gaps in our knowledge of how the pathogen behaves. This knowledge is key to developing both potential treatment and vaccine candidates.  Development of new interventions will be difficult, more time consuming, and more expensive without some or all of these enabling tools and knowledge. 

Finally, there is also considerable uncertainty about the nature of the Crypto burden. While GEMS established Crypto’s importance relative to other enteric pathogens, little is known about the longer-term consequences of infection, such as stunting and cognitive impairment. Less is known about the prevalence of asymptomatic infection and whether those infections can also lead to morbidity. The answers to these questions can have important implications for which interventions will best address the Crypto burden.  For instance, if asymptomatic infection represents a large part of the total burden, a vaccine strategy will likely impact a much greater portion of this burden than a treatment strategy, which will only affect those who are symptomatic. 

Opportunity for Change: How the Foundation is Thinking About Crypto

While Crypto presents many challenges, the Foundation is committed to reducing morbidity and mortality of children infected by this disease. Our goal is to accelerate development of new interventions, such as treatment or vaccines that will address the burden of this disease.  In particular, our approach will be geared toward three key goals:

  •   Clarify uncertainties in existing Crypto burden knowledge, which will enable us to identify which  interventions (such as treatment or vaccine) are likely to have the greatest impact on burden
  • Develop enabling tools that support multiple intervention types
  • Identify and advance promising candidates for treatment, since these likely have the shortest time frame to delivery

Together, these three sets of investments will build a foundation for determining how best to address the Crypto burden while providing the scientific tools needed to do so as quickly as possible. While many constraints and uncertainties exist, we are optimistic this approach will push us toward solutions that reduce the morbidity and mortality of Crypto while maintaining our ability to adapt to new information in this developing field.

 
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