Trypanosomiasis, human African (sleeping sickness)
- Sleeping sickness occurs only in 36 sub-Saharan Africa countries where there are tsetse flies that transmit the disease.
- The people most exposed to the tsetse fly and therefore the disease live in rural areas and depend on agriculture, fishing, animal husbandry or hunting.
- Trypanosoma brucei gambiense accounts for more than 98% of reported cases of sleeping sickness.
- Sustained control efforts have lowered the number of new cases. In 2009, the number of cases reported dropped below 10 000 (9878) for first time in 50 years and in 2012 there were 7216 cases recorded.
- Diagnosis and treatment of the disease is complex and requires specifically skilled staff.
Definition of the disease
Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. It is caused by infection with protozoan parasites belonging to the genus Trypanosoma. They are transmitted to humans by tsetse fly (Glossina genus) bites which have acquired their infection from human beings or from animals harbouring the human pathogenic parasites.
Tsetse flies are found just in sub-Saharan Africa though only certain species transmit the disease. For reasons that are so far unexplained, there are many regions where tsetse flies are found, but sleeping sickness is not. Rural populations living in regions where transmission occurs and which depend on agriculture, fishing, animal husbandry or hunting are the most exposed to the tsetse fly and therefore to the disease. The disease develops in areas ranging from a single village to an entire region. Within an infected area, the intensity of the disease can vary from one village to the next.
Forms of human African trypanosomiasis
Human African trypanosomiasis takes two forms, depending on the parasite involved:
- Trypanosoma brucei gambiense is found in 24 countries in west and central Africa. This form currently accounts for over 98% of reported cases of sleeping sickness and causes a chronic infection. A person can be infected for months or even years without major signs or symptoms of the disease. When more evident symptoms emerge, the patient is often already in an advanced disease stage where the central nervous system is affected.
- Trypanosoma brucei rhodesiense is found in 13 countries eastern and southern Africa. Nowadays, this form represents under 2% of reported cases and causes an acute infection. First signs and symptoms are observed a few months or weeks after infection. The disease develops rapidly and invades the central nervous system. Only Uganda presents both forms of the disease.
Another form of trypanosomiasis occurs mainly in Latin America. It is known as American trypanosomiasis or Chagas disease. The causal organism is a different subgenus from those causing the African form of the disease.
Other parasite species and sub-species of the Trypanosoma genus are pathogenic to animals and cause animal trypanosomiasis in wild and domestic animals. In cattle the disease is called Nagana.
Animals can host the human pathogen parasites, especially T.b. rhodesiense; thus domestic and wild animals are an important parasite reservoir. Animals can also be infected with T.b. gambiense and act as a reservoir. However the precise epidemiological role of the animal reservoir in the gambiense form of the disease is not yet well known. The disease in domestic animals, particularly cattle, is a major obstacle to the economic development of affected rural areas.
Major human epidemics
There have been several epidemics in Africa over the last century:
- one between 1896 and 1906, mostly in Uganda and the Congo Basin;
- one in 1920 in a number of African countries; and
- the most recent epidemic occurred in 1970 and lasted up to late 1990s.
The 1920 epidemic was controlled thanks to mobile teams which organized the screening of millions of people at risk. By the mid-1960s, the disease was under control with less than 5000 cases reported in the whole Continent. After this success, surveillance was relaxed, and the disease reappeared in several regions. The efforts of WHO, national control programmes, bilateral cooperation and nongovernmental organizations (NGOs) during the 1990s and the beginning of the 21st century stopped and reversed the upward trend of new cases.
Since the number of new human African trypanosomiasis cases reported between 2000 and 2012 has dropped by 73%, the WHO NTD Roadmap has targeted its elimination as a public health problem by 2020.
Distribution of the disease
Sleeping sickness threatens millions of people in 36 countries in sub-Saharan Africa. Many of the affected populations live in remote areas with limited access to adequate health services, which complicates the surveillance and therefore the diagnosis and treatment of cases. In addition, displacement of populations, war and poverty are important factors that facilitate transmission.
- In 1998, almost 40 000 cases were reported, but estimates were that 300 000 cases were undiagnosed and therefore untreated.
- During epidemic periods prevalence reached 50% in several villages in the Angola, Democratic Republic of Congo, and South Sudan. Sleeping sickness was the first or second greatest cause of mortality in those communities, ahead of even HIV/AIDS.
- In 2009, after continued control efforts, the number of cases reported dropped below 10 000 (9878) for first time in 50 years. This decline in number of cases has continued with 7216 new cases reported in 2012. However, the estimated number of actual cases is 20 000 and the estimated population at risk is 70 million people.
In 2000 and 2001, WHO established public-private partnerships with Aventis Pharma (now Sanofi) and Bayer HealthCare which enabled the creation of a WHO-led control and surveillance programme, providing support to endemic countries in their control activities and the supply of medicines free of charge.
The partnership was renewed in 2006 and in 2011. The success in curbing the number of sleeping sickness cases has encouraged other private partners to sustain the WHO’s initial effort towards eliminating the disease as a public health problem.
In 2013 WHO and the Bill and Melinda Gates Foundation signed an agreement to support and implement innovative strategies for case finding and surveillance to reach the sustainable elimination of the gambiense form of the disease.
Current situation in endemic countries
The prevalence of the disease differs from one country to another as well as in different parts of a single country.
- In the last 10 years, over 70% of reported cases occurred in the Democratic Republic of Congo (DRC).
- The DRC is the only country that has reported more than 1000 new cases annually and accounts for 83% of the cases reported in 2012.
- Central African Republic, Chad and South Sudan declared between 100 and 500 new cases in 2012.
- Countries such as, Angola, Cameroon, Congo, Côte d'Ivoire, Equatorial Guinea, Gabon, Ghana, Guinea, Kenya, Malawi, Nigeria, Uganda, United Republic of Tanzania, Zambia and Zimbabwe are reporting fewer than 100 new cases per year.
- Countries like Benin, Botswana, Burkina Faso, Burundi, Ethiopia, Gambia, Guinea Bissau, Liberia, Mali, Mozambique, Namibia, Niger, Rwanda, Senegal, Sierra Leone, Swaziland and Togo have not reported any new cases for over a decade. Transmission of the disease seems to have stopped but there are still some areas where it is difficult to assess the exact situation because the unstable social circumstances and/or remote accessibility hinders surveillance and diagnostic activities.
Infection and symptoms
The disease is mostly transmitted through the bite of an infected tsetse fly but there are other ways in which people are infected with sleeping sickness.
- Mother-to-child infection: the trypanosome can cross the placenta and infect the fetus.
- Mechanical transmission through other blood sucking insects is possible. However, it is difficult to assess the epidemiological impact of transmission.
- Accidental infections have occurred in laboratories due to pricks from contaminated needles.
In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph. This is known as a first stage or haemolymphatic phase, which entails bouts of fever, headaches, joint pains and itching.
In the second stage the parasites cross the blood-brain barrier to infect the central nervous system. This is known as the neurological or meningoencephalic phase. In general this is when more obvious signs and symptoms of the disease appear: changes of behaviour, confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is an important feature of the second stage of the disease. Without treatment, sleeping sickness is considered fatal although cases of healthy carriers have been reported.
Disease management: diagnosis
Disease management is made in three steps.
- Screening for potential infection. This involves using serological tests (only available for T.b.gambiense) and checking for clinical signs - generally swollen cervical glands.
- Diagnosing whether the parasite is present.
- Staging to determine the state of disease progression. This entails examining cerebrospinal fluid obtained by lumbar puncture and is also used to determine the outcome of treatment.
Diagnosis must be made as early as possible to avoid progressing to the neurological stage in order to elude complicated, difficult and risky treatment procedures.
The long, relatively asymptomatic first stage of T. b. gambiense sleeping sickness is one of the reasons why an exhaustive, active screening of the population at risk is recommended, in order to identify patients at an early stage and reduce transmission. Exhaustive screenings require a major investment in human and material resources. In Africa such resources are often scarce, particularly in remote areas where the disease is mostly found. As a result, some infected individuals may die before they can ever be diagnosed and treated.
The type of treatment depends on the stage of the disease. The drugs used in the first stage of the disease are of lower toxicity and easier to administer. The earlier the disease is identified, the better the prospect of a cure.
Treatment success in the second stage depends on a drug that can cross the blood-brain barrier to reach the parasite. Such drugs are toxic and complicated to administer. Four drugs are registered for the treatment of sleeping sickness. These drugs are donated to WHO by manufacturers and distributed free of charge to countries endemic for the disease.
First stage treatment:
- Pentamidine: discovered in 1941, used for the treatment of the first stage of T.b. gambiense sleeping sickness. Despite non-negligible undesirable effects, it is in general well tolerated by patients.
- Suramin: discovered in 1921, used for the treatment of the first stage of T.b. rhodesiense. It provokes certain undesirable effects, in the urinary tract and allergic reactions.
Second stage treatment:
- Melarsoprol: discovered in 1949, it is used in both forms of infection. It is derived from arsenic and has many undesirable side effects. The most dramatic is reactive encephalopathy (encephalopathic syndrome) which can be fatal (3% to 10%). An increase in resistance to the drug has been observed in several foci particularly in central Africa.
- Eflornithine: this molecule, less toxic than melarsoprol, was registered in 1990. It is only effective against T.b. gambiense. The regimen is strict and difficult to apply.
- A combination treatment of nifurtimox and eflornithine was introduced in 2009. It simplifies the use of eflornithine in monotherapy, but unfortunately it is not effective for T.b. rhodesiense. Nifurtimox is registered for the treatment of American trypanosomiasis but not for human African trypanosomiasis. Nevertheless, after safety and efficacy data provided by clinical trials, its use in combination with eflornithine has been accepted and included in the WHO List of Essential Medicine, and it is provided free of charge for this purpose by WHO to endemic countries.
WHO provides support and technical assistance to national control programmes.
WHO provides the medicines free of charge to endemic countries through a private partnership with Sanofi (pentamidine, melarsoprol and eflornithine) and Bayer AG (suramin and nifurtimox).
In 2009, WHO set up a specimen bank that is available to researchers to facilitate the development of new and affordable diagnostic tools. The bank contains samples of blood, serum, cerebrospinal fluid, saliva and urine from patients infected with both forms of the disease as well as samples from uninfected people from areas where the disease is endemic.
The objectives of the WHO Programme are to:
- strengthen and coordinate control measures and ensure field activities are sustained;
- strengthen surveillance systems;
- ensure accessibility to diagnostic and treatment;
- support the monitoring of treatment and drug resistance;
- develop an information database and epidemiological analysis of data, including the atlas of the human African trypanosiomiasis, completed in collaboration with the Food and Agriculture Organization (FAO);
- ensure skilled staff by offering training activities;
- support operational research to improve diagnostic and treatment tools;
- promote collaboration with the FAO in charge of animal trypanosomiasis and the International Atomic Energy Agency (IAEA) dealing with vector control through male flies made sterile by radiation. The 3 UN agencies along with the African Union have promoted the Programme Against African Trypanosomiasis (PAAT);
- synergize vector and human control activities in collaboration with the Pan African Tsetste and Trypanosomosis Eradication Campaign (PATTEC) of the African Union.
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