Eliminating sleeping sickness for good

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After recent gains against trypanosomiasis, new diagnostic and treatment tools mean we can make the final push, says Priya Shetty.

Once again we are close to eliminating sleeping sickness, or human African trypanosomiasis — a disease discovered a century ago.

The first time, buoyed by the success of control programmes in the 1930s, governments and global health experts relaxed their efforts and the disease returned with a vengeance. Estimates suggest that in 1995, about 300,000 people were infected with the Trypanosoma brucei parasite.

But by 2009, the number of new cases of the disease fell below 10,000 for the first time in 50 years, according to a recent report in PLoS Neglected Tropical Diseases.

This remarkable drop in the incidence of the disease was the result of a well-coordinated effort from the WHO, nongovernmental organisations, pharmaceutical companies and disease-endemic African countries. The WHO spearheaded surveillance and vector control efforts, and companies provided drugs free of charge. Such cohesive action is all too rare in global health.

The drop in incidence is all the more impressive because it relied on drugs whose effectiveness was far from ideal, and diagnostic methods that are not especially sensitive.

Now, for the first time in the history of sleeping sickness, we have new diagnostics and new drug candidates to fight it. This is the right moment for the global health community to use new and existing methods to eliminate the remaining 10,000 cases.

Stopping transmission

An obvious way to stop a vector-borne disease is to eliminate the vector. The parasites that cause sleeping sickness are transmitted to people through the bite of tsetse flies, which are native to Sub-Saharan Africa.

Last month, researchers reporting on a study from a group of islands off West Africa showed that it was possible to eliminate tsetse flies by bombarding them with different control techniques, from poison-impregnated traps and targets to ground-spraying.

Animals such as pigs and cattle act as secondary vectors — the flies feed on their blood and then bite people, spreading the parasites. To block this step in transmission, the research team smeared the pigs with insecticide, and set up insecticide-impregnated fences around the pig pens.

In Uganda, experts in animal disease control are encouraging farmers to treat their cattle for ticks and tsetse flies, and for infection. This method has also been successful in Zambia and Burkina Faso.

Easier diagnostics

But detecting sleeping sickness is difficult. The symptoms are similar to those of malaria, and people can develop the disease even with low levels of parasites in their body, which means that a test needs to be highly sensitive to spot them.

Another complication is that diagnostic techniques need to differentiate between the two different strains of parasite, T. b. rhodesiense and T. b. gambiense, because they cause different types of disease and need different treatments.

DNA-based diagnostic tools promise to speed up detection of the parasites. In particular, loop-mediated isothermal amplification (LAMP) of DNA can detect T. b. rhodesiense with a sensitivity of up to one trypanosome per millilitre of blood — a vast improvement from the 10,000 parasites per millilitre for existing light microscopy methods.

And unlike some DNA amplification techniques, LAMP works at a lower temperature of 60–65 degrees Celsius, which can be maintained without special equipment.

Samples that contain the parasite change colour, making for easy visual detection. Importantly, the simplicity of the test means that it would be appropriate for rural, resource-poor settings.

A major barrier to improving the tools used to diagnose sleeping sickness is that, as with other neglected diseases, there is little incentive for pharmaceutical companies to invest in them. But some disease detection methods can be used for multiple diseases, offering a bigger payback.

For instance, a fluorescence microscope with a light-emitting diode (LED) that was developed for tuberculosis can also be used to detect T. brucei parasites. Like the LAMP DNA test, it is suitable for use in Sub-Saharan Africa.

It resists interference from DNA inhibitors, which means it can be used in less than pristine lab conditions, and it is inexpensive. The microscope uses solar-powered LED bulbs with a lifespan of more than 10,000 hours.

Medical scientists in Uganda and the Democratic Republic of the Congo have already used it to diagnose sleeping sickness.

New treatment targets

Existing treatments for sleeping sickness are far from ideal. Most drugs cause severe side effects — and an arsenic-based drug called melarsoprol is fatal for one in 20 patients. Other treatments are costly and complicated to administer.

But the sequencing of the T. brucei genome is helping scientists to search for new drug targets.

Last year, a team from the UK and Canada discovered a compound that disrupts an enzyme (N-myristoyl transferase, or NMT) which is vital for the growth of the parasites, and proved successful at treating the disease in mice.

And last October, researchers released a rough draft of the tsetse fly genome. Investigating molecular interactions between the fly and the trypanosome could offer valuable insights into ways of blocking the vector’s ability to transmit the parasite.

The global health community has a much bigger toolbox to fight sleeping sickness than it did the last time elimination was in sight, early in the twentieth century. Now is the time to capitalise on recent successes and eliminate the disease once and for all.

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