NTDs: Human African trypanosomiasis – a fly bite can lead to neurological issues and death

This post is the 8th in a series highlighting the WHO’s list of 17 Neglected Tropical Diseases (now technically 18 as mycetoma was added to the list at the 69th World Health Assembly in May 2016). To read the previous posts in this series click here.

Trypanosoma brucei

Trypanosoma brucei and its vector, the tsetse fly. Courtesy CDC.

Human African trypanosomiasis (sleeping sickness) is a fatal parasitic disease that occurs in 36 sub-Saharan Africa countries, putting 61 million people at risk. Most of the people at risk live in rural areas and depend on agriculture, fishing, animal husbandry or hunting to survive. Sleeping sickness is caused by infection with a protozoan parasite, genus Trypanosoma, and the parasite is transmitted through the bite of a tsetse fly. The flies get the parasite from either infected humans or infected animals and then pass it along when they bite the next animal or human.

Courtesy CDC.

The interesting thing about tsetse flies is that they are found only in sub-Saharan Africa; but, for unexplained reasons, in many regions where you can find the tsetse fly there is no sleeping sickness. Sleeping sickness can develop in areas ranging from an entire village to an entire region, but even in an affected region, the severity of illness can vary from one village to another.

The parasites that cause sleeping sickness come from two different subspecies of Trypanosoma brucei, T.b. gambiense and T.b. rhodesiense. Each sub-species causes different forms of sleeping sickness. Trypanosoma brucei gambiense is responsible for around 98% of reported cases and causes chronic infection. A person infected with T.b. gambiense can be infected for years without showing symptoms and when they do start to show major symptoms, mostly neurological symptoms, the disease is already in an advanced stage. In comparison, T.b. rhodesiense only causes about 2% of sleeping sickness cases and it causes an acute infection where symptoms appear within weeks or months and the disease quickly progress to invade the neurological system.

The Trypanosoma sub-species generally live in separate geographic areas. Trypanosoma brucei gambiense is found in 24 countries in west and central Africa. Trypanosoma brucei rhodesiense is found in 13 countries in eastern and southern Africa. The only country where both sub-species can be found is Uganda, but even then they are found in different parts of the country.

HAT_map_AR14

Geography of the two subspecies of Trypanosoma brucei that cause African sleeping sickness. Courtesy DNDi.

The seven most affected countries (see map above, “Epidemic” countries) account for 97% of cases. The Democratic Republic of Congo accounted for 89% of all reported cases in 2013.

There have been several epidemics of sleeping sickness in Africa over the last century, the most recent started in the 1970s and lasted until the late 1990s. Prior to the outbreak that started in 1970, control measures had decreased the case count into the 5 000s, but as can probably be expected, surveillance and control measures were relaxed and cases of sleeping sickness reappeared in large numbers, leading to the 1970 – late 1990s outbreak.

Even though the majority of cases are found in only a few countries, the total number of cases of Human African trypanosoma has been decreasing. In 2009, the number of cases dropped below 10 000 for the first time in 50 years. In 2014 there were 3796 cases reported. And in 2015, there were less than 3 000 new cases reported. However, sleeping sickness is hard to diagnose so the reported cases probably represent only a fraction of the real number of cases.

Diagnosing sleeping sickness is challenging. The mild initial symptoms of infection with T.b. gambiense mimic other less serious illnesses. Diagnosis must be made early to prevent the disease from progressing to the neurological stage. Screening for cases is vital but it requires serological tests (for T.b. gambiense only) and once the parasite is found in the body fluids, doing a lumbar puncture to examine the cerebrospinal fluid to determine the state of disease progression.  Since T.b. gambiense has a long, relatively asymptomatic period, exhaustive, active screening programs are required to test and treat people early in their infection. But as you can probably imagine, this level of screening requires a ton of time and resources that some affected communities just do not have.

WHO has targeted Human African trypanosomiasis for elimination as a public health problem by 2020. The goal of elimination may be realistically possible due to the success of the control programs which have resulted in a drastic decrease in cases. Additionally, medication is available to treat and cure sleeping sickness, although treatment in the earlier stage (prior to the parasite getting into the brain, which is the second stage) is much easier and less toxic than treatment than the second stage. Drug manufacturers donate medication to WHO and WHO partners with MSF (Doctors without Borders) to distribute the drugs to countries free of charge. MSF also has mobile teams to screen for sleeping sickness in rural areas where transmission is still active. Check out this cool video of MSF staff in the field.

It should also be noted that Human Africa trypanosomiasis is related to American trypanosomiasis, also known as Chagas disease, which mainly occurs in Latin America. Chagas disease is transmitted by a different Trypanosoma subgenus and different vector. But the parasites are related, which means that scientists can develop one drug to treat the different diseases. And they have. Scientists published results in Nature that indicate they developed a successful drug that targets an enzyme shared among the parasites to treat sleeping sickness, Chagas and leishmaniasis. This drug was shown to cross the blood-brain barrier in mice, effectively targeting the parasites once they’ve moved into the brain.

Targeting sleeping sickness for elimination by 2020 seems to be a large, ambitious goal to me. Especially with the current challenges in screening people for the disease and the lack of accurate surveillance data due to those screening challenges. 2020 is only four years away, so it will be interesting to see if the world can eliminate sleeping sickness during the next few years.

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