INCIDENCE OF AFRICAN TRYPANOSOMIASIS (1977 –1999)
Source: Report of the Expert Committee, 1992 and Dr J. Jannin, 2000
The social and economic impact of sleeping
sickness is often underestimated. Epidemics have serious social and
economic consequences and the disease has been a major cause of
depopulation of large tracts of Africa. The fear it causes has led to
abandonment of fertile lands, and is an impediment to development. The
disease mainly strikes the active adult population.
Regular active surveillance, involving case detection and treatment, and where applicable, tsetse fly control, is the backbone of the strategy for control of sleeping sickness. Systematic screening of communities in identified foci is the best approach as case-by-case screening is not practically possible in highly endemic regions. Systematic screening may be in the form of mobile clinics or fixed screening centres where teams travel daily to the foci. The nature of gambiense disease is such that patients don’t seek treatment early enough because the symptoms at that stage are not evident or serious enough to warrant seeking medical attention, considering the remoteness of some affected areas. Also, diagnosis of the disease is difficult and most health workers may not be able to detect it. Systematic screening allows early-stage disease to be detected and treated before the disease progresses, and removes the potential human reservoir. Therefore, the systematic screening of communities in identified foci is essential for the surveillance programme to be effective.
Also for surveillance to be effective, it is important to train the teams responsible for systematic screening. About 80%of endemic countries have national control programmes which are responsible for identifying the teams and through which appropriate training (in diagnosis, treatment) can be provided or requested.
The national control programmes are encouraged to form networks so that they can share ideas and experiences, and to closely collaborate with NGOs and other bodies involved in control activities. The WHO Communicable Disease Surveillance and Response (CDS/CSR) unit is actively helping endemic countries to establish national control programmes. It is also responsible for coordination of the Human African Trypanosomiasis Treatment and Drug Resistance Network that has as its objectives: to assess the effectiveness of current treatment regimens, collect and disseminate information on refractoriness to treatment, ensure availability and affordability of existing drugs, provide guidelines for treatment, and promote research on drugs and treatment and causes of treatment failures.
Another element of control is to strengthen
the treatment capability of control programmes by looking at drug
availability, increasing research capacities, monitoring drug resistance,
geographical information system (GIS) mapping of the foci. With the tools
available today, continual control, rather than eradication, is possible.
Significant resurgence of the disease has occurred, notably in Angola, DRC, Uganda and Sudan, in recent years, and new foci of the disease have emerged. The persistence and re-emergence of sleeping sickness is attributable to a number of factors, which constitute challenges for control.
Means for regular surveillance are often inadequate while, at the individual and family levels, there may be inadequate knowledge of disease symptoms, transmission dynamics and treatment. Population movements due to seasonal migration and refugees, may increase human-fly contact and hinder regular medical surveillance of the population at risk. In rhodesiense sleeping sickness, cattle movements also increase the risk of infection. Agro-ecological changes may alter tsetse habitat and increase human-fly contact.
The chemotherapy of African trypanosomiasis relies on a few drugs which have adverse side-effects and are unsatisfactory: pentamidine for early-stage T. b. gambiense sleeping sickness, suramin for early-stage T. b. rhodesiense sleeping sickness, and melarsoprol for late-stage disease of both forms of sleeping sickness. Increasing numbers of patients, 20-25% in certain foci, do not respond to melarsoprol treatment, probably due to resistance, but this needs to be proven. Eflornithine is the only alternative registered drug for the treatment of T. b. gambiense sleeping sickness patients who do not respond to melarsoprol. However, apart from other drawbacks, it costs $US 300-500 per patient. Nifurtimox, although not registered for African trypanosomiasis, has been used experimentally and on compassionate grounds for T. b. gambiese sleeping sickness patients who did not respond to melarsoprol, with varying results. New drugs that are safe, effective and affordable are needed.
Ministries of health, research organizations and services often lack or do not have adequate economic resources for sleeping sickness control programmes due to competing health priorities. Recruitment of medium-level personnel is inhibited by lack of incentives and career prospects. Ministries may lack funds for the purchase of diagnostic tests and drugs, except as part of externally-funded programmes.
Other factors that increase the risk of infection are agricultural developments such as coffee and cocoa plantations, and the tourism industry, both of which increase human-fly contact.
Central governments often accord sleeping
sickness a low priority, until it assumes epidemic proportions. In
addition, political upheavals, civil strife and wars lead to breakdown of
health services, and hence of control programmes.
Long-term commitment, rather than support as crisis management, by governments of endemic countries and the international community to national sleeping sickness control programmes is essential for sustained control, as African trypanosomiasis afflicts the poorest of African countries.
Factors that militate against the effective use of existing tools, such as continued worsening economies and structural adjustment programmes in the affected countries should be addressed.
There is an urgent need for better tools .More effective, affordable and more tolerable drugs are needed. With the exception of eflornithine that was registered for human African trypanosomiasis in 1990,no new drug has been developed in over 50 years due to lack of interest by industry. Tests are needed to diagnose late-stage disease and to determine cure after treatment.
There is a need for implementation strategies that are better adapted to the health systems and socioeconomic constraints in the endemic countries. Simple surveillance systems are needed, that can be integrated into available capacities to improve case detection, permit earlier diagnosis of cases, and establish the prevalence of resistance to melarsoprol. Research is needed on how to effectively apply the available tools with the existing capacities,including in the health services, strong control programmes for other diseases, NGOs.
There is need for more basic knowledge in relation to drug resistance, risk factors for the resurgence and persistence of African trypanosomiasis, and the significance of animal reservoirs of T. b. gambiense.
There is need for capacity building for
research and control of human African trypanosomiasis in the endemic
countries through strengthening laboratories and research centres,
training scientists, and encouraging networking.
The Scientific Working Group (SWG) on African Trypanosomiasis met in June 2001. It brought together a multidisciplinary group of scientists, partners and collaborators from academia, public and private sectors, sleeping sickness control programmes, and both endemic and non-endemic countries. The objectives of the meeting were to chart out a global research agenda on African trypanosomiasis, closely linked to control needs and open to opportunities arising from basic science, to guide TDR and others interested in research on African trypanosomiasis, and to provide data for use in advocacy to convince policy makers and donor agencies to place control of the disease higher on their agendas.
The meeting provided an opportunity to: identify the knowledge that could be exploited for developing new tools for disease and vector management, and improving existing tools; determine the needs for research capability strengthening in disease endemic countries for basic sciences. TDR ’s comparative advantage in enhancing the existing and developing new partnerships for maximal application of the available knowledge was highlighted. The SWG recommendations fell within the following emphases:
Advocacy for long-term commitment
New and better tools
Improved implementation strategies
The trypanosome, due to its many unique biological characteristics, is one of the most studied parasites and offers many opportunities for basic research. Though it is difficult to get funds for the control of sleeping sickness, important sums of money are invested annually, particularly in the North, on basic research on African trypanosomes. There is probably more information on the biochemistry and molecular biology of trypanosomes than any other non-mammalian cell type and a great deal is known about the differences between trypanosomes and mammalian cells, and yet no drug has yet been designed rationally.
TDR ’s drug discovery programme comprises integrated screening of molecules from the chemical libraries of pharmaceutical companies and academia against African trypanosomes, T. cruzi, Leishamania, and malaria parasites. The TDR drug development portfolio comprises the development of an oral formulation of eflornithine, which has many advantages, apart from ease of administration, over the injectable formulation. TDR operational research activities include evaluation of the card indirect agglutination test for trypanosomiasis (CIATT), and of treatment with pentamidine of serologically positive individuals who are not proven parasitologically positive with T. b. gambiense.
The Bill & Melinda Gates Foundation
recently awarded US$15 million to a consortium of scientists for the
development of drugs for African trypanosomiasis and leishmaniasis.
TDR has links with the outside world of product development. Over its lifetime, TDR has generated multiple partnerships for product development and has gained considerable experience. It has successfully taken some products up to registration in collaboration with the private sector, e.g. mefloquine, flornithine, AmBisome.
TDR provides an essential link between research institutions in the North and endemic countries, through access to a network of national field projects and control programmes, where spin-offs from basic research can be evaluated as tools for the control and prevention of sleeping sickness. A successful example is the card agglutination test for trypanosomiasis (CATT), that evolved from studies on the variant surface glycoproteins (VSGs) in trypanosomes. TDR could preserve this unique role by introducing seed money where likely spin-offs from basic research will be of public health importance.
For institutions in the South, TDR has been a conspicuous source of funding for research on African trypanosomiasis and institutional strengthening activities. Consequently, drastic reduction in funding in TDR for African trypanosomiasis, which started in 1994, has had adverse effects on trypanosomiasis research in the endemic countries, in terms of human resources and institutional capabilities.
During 1993/94,TDR initiated global parasite
genome networks for T. b. brucei, T. cruzi, Leishmania major,
Schistosoma mansoni, and Brugia malayi. The networks are now
orientated towards post genomics, and bioinformatics networks are being
expanded for data mining, annotation and in-depth analysis.
1. World Health Organization. World Health Report 2000 Health Systems Improving Performance Geneva, 2000.
2. WHO Expert Committee on Control and Surveillance of African trypanosomiasis Geneva, World Health Organization, 1998 (WHO Technical Report Series,No.881).
3. Shaw APM et al. Report of the Scientific Working Group meeting on African trypanosomiasis, June 2001, Annex 4 III.
4. TDR Scientific Working Group, June 2001.World Health Organization, Geneva.