What is African sleeping sickness?

What is trypanosomiasis?

• Trypanosomiasis refers to a group of diseases caused by Trypanosoma parasites.
• There are two types of trypanosomiasis that affect humans, they are divided according to their geographical location:
  • African trypanosomiasis, or sleeping sickness, is caused by Trypanosoma brucei parasites in sub-Saharan Africa and is transmitted by the tsetse fly (Glossina).
  • American trypanosomiasis, or Chagas disease, is caused by Trypanosoma cruzi parasites in Latin America and is transmitted by the triatomine or ‘kissing’ bug.
• Trypanosomiasis can also affect animals. Nagana disease is a form of trypanosomiasis that affects vertebrate animals such as cattle. It is caused by several kinds of Trypanosoma including Trypanosoma brucei and Trypanosoma vivax.
• Animals, such as wild game and domestic animals, can also act as a reservoir host for the human trypanosome parasites. While wild animals are mostly tolerant to the disease, for domestic animals, the infection can be severe and sometimes fatal.

Scanning electron micrograph (SEM) of a Trypanosoma brucei parasite.

Image credit: Gull Lab courtesy of Sue Vaughan, Wellcome Images

What is human African trypanosomiasis (sleeping sickness)?

• African trypanosomiasis occurs in 36 countries in sub-Saharan Africa.
• Around 10,000 new cases of African trypanosomiasis are reported each year. However, it is estimated that many cases go undiagnosed.
• African trypanosomiasis is caused by two species of Trypanosoma brucei: Trypanosoma brucei gambiense (West African) and Trypanosoma brucei rhodesiense (East African).
• Trypanosoma brucei gambiense is responsible for more than 98 per cent of all reported cases of human African trypanosomiasis and causes chronic infection.
• Trypanosoma brucei rhodesiense is responsible for under 2 per cent of all reported cases of human African trypanosomiasis and causes acute infections that develop rapidly over a few weeks.
• Another type of trypanosome, Trypanosome brucei brucei, does not affect humans.

How is African trypanosomiasis transmitted?

• Both species of Trypanosoma are transmitted from human to human through the bite of the tsetse fly (Glossina) which is only found in rural parts of Africa.
• However, trypanosomes can also be transmitted from mother to child as the parasite can cross the placenta in the blood and infect the baby while it is still in the womb.
• Contaminated needles can also contribute to the spread of trypanosomes, but this is rare.
• Communities most at risk of trypanosomiasis live in rural areas where the tsetse fly is found. These communities often depend primarily on agriculture, fishing and hunting to survive and have limited access to health services and education. As a result, many cases of trypanosomiasis go undiagnosed.

The tsetse fly.
Image credit: Wellcome Library, London

Trypanosome life cycle

• The trypanosome parasite is first introduced into the mammalian host when a tsetse fly takes a blood meal and secretes parasite-filled saliva into the host’s skin.
• At this stage of the life cycle the parasites are in their infective form, called metacyclic trypomastigotes, which have a short, free flagellum.
• Once in the bloodstream, the parasites transform into slender trypomastigotes with a longer flagellum which then spread rapidly to other areas of the body in the blood.
• The trypomastigotes multiply in the blood, lymph or spinal fluid.
• In the mammalian bloodstream, the trypomastigotes have different forms:
  • a long slender form
  • a short, stumpy form
  • an intermediate form between the two.
• The short stumpy form is pre-adapted for survival in the tsetse fly so is the form that differentiates into the next stage of the life cycle when the fly takes a blood meal from an infected mammalian host.
• Once inside the midgut of the tsetse fly, the trypomastigotes transform into procyclic trypomastigotes, which multiply in the gut.
• After multiplying, the procyclic trypomastigotes move to the front (anterior) of the midgut en route to the tsetse fly’s salivary gland.
• On this journey, the procyclic trypomastigotes then develop into epimastigotes which migrate to the tsetse fly’s salivary gland and attach to the wall of the gland by their flagella.
• Finally, the epimastigotes transform into short, infective metacyclic trypomastigotes and detach from the wall of the salivary gland, ready to be injected into a new host when the fly takes another blood meal.

Illustration of the life cycle of the trypanosome parasite that causes African sleeping sickness.
Image credit: Genome Research Limited

What are the symptoms of African trypanosomiasis?

• The symptoms of African trypanosomiasis are divided into two key stages:
  • First stage or haemolymphatic phase: shortly after the metacyclic trypomastigotes enter the body and multiply under the skin an inflammatory reaction occurs. This causes swelling of the skin and enlargement of the lymph nodes in the neck. This immune response results in symptoms such as fever, headaches, joint pains and itching.
  • Second stage or neurological phase: this stage begins when the trypanosome parasites cross from the blood-brain barrier into the spinal fluid, infecting the central nervous system including the brain. Once the brain is affected it results in changes in behaviour, confusion, poor coordination, difficulties with speech and disturbance of sleep (sleeping through the day and insomnia at night), hence the term ‘sleeping sickness’.
• Without treatment, African trypanosomiasis is fatal.

Screening and diagnosis of African trypanosomiasis

• Diagnosis of African trypanosomiasis must be made as early as possible to prevent the disease from progressing into the second stage.
• Trypanosomiasis is a disease of rural areas, where there is limited access to medical help or education about the symptoms to look out for. As a result many sufferers go undiagnosed and consequently do not receive the treatment they need.
• To try and avoid this happening, screening programmes have been put in place for some at-risk populations. Screening involves two steps:
  1. Checking for clinical signs, such as swollen lymph glands in the neck and neurological signs such as an altered mental state or extended daytime sleeping.
  2. Examining blood smears for signs of the parasite.

Blood smear taken from an individual with trypanosomiasis (pink circles are red blood cells; purple swirls are trypanosome parasites).
Image credit: CDC/Dr. Myron G. Schultz. Centers for Disease Control and Prevention’s Public Health Image Library (PHIL) #613

• If these tests are inconclusive, individuals may have a blood test for specific antibodies that signify the parasite is present.
• If these test results come back positive and show that an individual has trypanosomiasis then there is a further assessment to find out which stage the disease has progressed to.
• This involves taking a sample of spinal fluid via a lumbar puncture and examining the sample for parasites. If parasites are present this indicates that the disease has progressed to the neurological phase.
• Screening of at-risk populations is a major investment, both in terms of the number of people needed to do them and the materials required (which are often scarce in the areas of Africa where trypanosomiasis is found).
• However, it is a necessary investment as many people infected with trypanosomiasis are undiagnosed and do not receive treatment. This increases the level of transmission and could eventually lead to the disease reaching epidemic levels.
• There have been several epidemics of trypanosomiasis in Africa over the last century. In 1920, an epidemic was controlled as a result of screening millions of people at risk. This resulted in less than 5,000 cases of the disease by the mid-1960s.
• However, as a result of this success, screening was relaxed. The disease soon started to reappear again in several areas, highlighting the need for ongoing surveillance.

How is trypanosomiasis treated?

• Trypanosomiasis is curable if treatment is given quickly, however if left untreated the disease is fatal.
• The type of treatment given depends on the stage of the disease. Generally, the earlier the disease is identified, the easier it is to treat.
• The drugs that are used to treat trypanosomiasis when it is in the first stage of the disease, generally have milder side effects and are easier to administer, usually in the form of a series of injections.
• Once in the second stage of the disease, when the parasite has crossed the blood-brain barrier, treatment becomes much more aggressive with more toxic drugs needed to kill the parasite. These drugs are also more complicated to administer, usually requiring several weeks of drugs being given intravenously (directly into the veins).
• Currently, four drugs are registered for treating African trypanosomiasis and are administered free of charge to countries where the disease is a problem. These include:
  • Pentamidine – used to treat first stage Trypanosoma brucei gambiense, it generally has no adverse side effects.
  • Suramin – used to treat first stage Trypanosoma brucei rhodesiense, it causes some side effects such as urinary tract infections and allergic reactions.
  • Melarsoprol – used to treat second stage Trypanosoma brucei rhodesiense. It is derived from arsenic and has many unwanted side effects. In extreme cases, it has been seen to cause reactive encephalopathy (disorder of the brain) which can be fatal. There has also been a spread of resistance to melarsoprol in trypanosomes found in central Africa.
  • Eflornithine – originally developed as an anti-cancer drug, it is used to treat second stage Trypanosoma brucei gambiense. It is less toxic than melarsoprol but can cause vomiting, diarrhoea and anaemia.

How can trypanosomiasis be prevented?

• There is currently no vaccine or preventative drug to help protect against African trypanosomiasis.
• Prevention is therefore generally aimed at minimising contact with the tsetse fly vector.
• Measures include:
  • wearing long-sleeved shirts and long trousers to limit the amount of exposed skin
  • wearing clothes in neutral colours as tsetse flies are attracted to bright colours
  • avoiding bushes where the tsetse fly rest during the hottest part of the day as they will bite if disturbed
  • using insect repellent such as DEET.
• Control of African trypanosomiasis currently centres around two key strategies:
  1. Population screening to ensure early treatment of infected people and help reduce the number of people carrying trypanosomiasis. Fewer people carrying the parasite means the tsetse fly is less likely to become infected when they take a blood meal and less likely to pass the parasite on to another individual at their next blood meal.
  2. Reducing transmission via the tsetse fly by using insecticides to kill the insect and deploying fly traps and/or screens in homes to reduce the number of flies entering.

Insecticidal spraying against tsetse fly in Nigeria.
Image credit: Wellcome Library, London