CryptoT&T

The challenge

Diarrhoeal diseases continue to be a leading cause of death among young children in low- and middle-income countries. Such diseases are caused by a wide range of bacteria, viruses and parasites. One of the most common is Cryptosporidium, a single-celled parasite. 

Cryptosporidium appears to cause more disease than once thought. The landmark international GEMS study, for example, identified Cryptosporidium as the third most common cause of diarrhoeal disease in young children, and one of three infections associated with an increased risk of death in children less than two years old. An estimated 2.9 million cases occur each year in sub-Saharan Africa, leading to more than 200,000 deaths in Africa and South Asia.

These deaths are avoidable, as an effective and affordable treatment for Cryptosporidium already exists, nitazoxanide. Currently, however, the drug is not widely used as the symptoms of Cryptosporidium infection are the same as many other diarrhoeal diseases, and there are no affordable diagnostics that could be used to identify cases caused by Cryptosporidium.

The project

The CryptoT&T project aims to overcome this barrier by using a microscope-based approach for identifying Cryptosporidium in faecal samples. LED microscopy of faecal samples treated with a particular stain (auramine-phenol) is a relatively simple technique requiring minimal training. Moreover, LED microscopy has already been introduced in many parts of sub-Saharan Africa to detect mycobacteria.

The project is exploring whether LED microscopy could be used as part of a test-and-treat strategy: patients with diarrhoeal disease would be routinely screened and provided with nitazoxanide when Cryptosporidium is detected. A recent study in Ethiopia showed that the technique has high sensitivity, but a larger study is needed to demonstrate that the test-and-treat strategy improves clinical outcomes, specifically in reducing the duration of cryptosporidiosis-induced diarrhoea.

As a treatment is available, a placebo-controlled trial would not be ethical. The project therefore uses a ‘stepped wedge’ design, in which the intervention is introduced over time, with areas scheduled for late-stage implementation serving as control sites. Ultimately, all facilities within the trial area will be using the strategy by the end of the study.

The key to success will be the speed at which results are generated, since the goal is to enable treatment to begin while a patient is at a health facility. One way to decrease the total turnaround time could be to use faecal smears rather than stool samples. The project will therefore run a study in parallel to compare the results obtained with the analysis of faecal smears and stool samples.

The study will run in a diverse set of sites around Addis Ababa and different provinces of Mozambique to provide data from different types of settings. It will also estimate the cost implications of the test-and-treat strategy and carry out a cost-effectiveness analysis. The project aligns with the UN Sustainable Development Goal 3 and the WHO initiatives to reduce the burden of diarrheal diseases.

Impact

The CryptoT&T project has the potential to impact the treatment of diarrhoeal disease significantly. It will:

• Generate critical data on the feasibility and cost-effectiveness of a test-and-treat strategy for Cryptosporidium infections.
• Facilitate the introduction of an affordable and targeted drug treatment, nitazoxanide.
• Strengthen surveillance systems and provide additional data on the prevalence of Cryptosporidium.
• Reduce the unnecessary use of antibiotics, the driving force of antibiotic resistance.

If the expected clinical impacts are seen, the CryptoT&T project could lead to much wider use of nitazoxanide, reducing the short-term impact of Cryptosporidium infections and, over the longer term, the harms associated with growth faltering triggered by repeated enteric infections.