UNDP/WORLD BANK/WHO Special Programme for Research and Training in Tropical Diseases (TDR)
Many people in the tropics suffer from poor nutrition, poor living conditions and a poor environment---and from the poor health that such conditions bring. They therefore suffer most of the diseases that affect mankind throughout the world. But on top of this burden, they must endure the heavy consequences of diseases specific to their situation: the so-called tropical diseases.
These diseases---such as malaria, schistosomiasis, lymphatic filariasis, Chagas disease, onchocerciasis, leishmaniasis, leprosy and African sleeping sickness---cause tremendous pain and suffering, from deformities to blindness, brain damage and death.
As Dr Hiroshi Nakajima, Director-General of the World Health Organization, puts it, "beyond their toll of individual illness and death, these tropical diseases impede national and individual development, make fertile land inhospitable, impair intellectual and physical growth, and exact a huge cost in treatment and control programmes".
Tropical diseases were once considered diseases of the rural poor. They still are; but today they are also becoming diseases of development, closely associated with people's need to earn income---for example, with the recent massive migration from rural to urban areas, and with new irrigation and mining projects. The diseases have become "the diseases of the new frontier" the diseases which rob people of their hope.
Nor are these diseases confined to the tropics. Tourism, trade, business travel and immigration are bringing cases of the diseases into the industrialized world, where health systems are unused to diagnosing them. Diagnoses often come too late, and case fatalities are unacceptably high. Tropical diseases should therefore be matters of global concern. They have been of the highest priority to the World Health Organization from its very first days of existence.
But tropical diseases are tenacious and have not easily given ground. There have been some successes: for example, since the 1950s, malaria has been eradicated from areas inhabited by 1.5 billion people, and mortality has been widely reduced; leprosy is declining in some countries because of the use of an effective new treatment; river blindness has declined in West Africa because of control of the blackflies that carry the parasite, and should decline further because of an effective new drug; Chagas disease vectors are being effectively controlled in Brazil and other parts of Latin America.
Yet even with these and other successes, the control of tropical diseases is nowhere near complete. Almost half a billion people still suffer from them. Existing tools for treatment and control need to be more widely applied, and new tools need to be developed. Advising on the use of existing tools, and the development of new ones, are two of the tasks of the WHO Division of Control of Tropical Diseases (CTD) and the Special Programme for Research and Training in Tropical Diseases.
The Special Programme for Research and Training in Tropical Diseases (TDR)---cosponsored by the United Nations Development Programme, the World Bank and the World Health Organization---was conceived in response to a 1974 plea by the World Health Assembly for an intensive effort to develop improved techniques for the control of tropical diseases. TDR has two interdependent objectives: to coordinate and support scientific research aimed at developing new or improved approaches to diagnosis, patient care, treatment and control, and to strengthen (for example with training grants and institutional support) the research capabilities of endemic countries. TDR links some 5000 scientists in 135 countries, North and South, in a globally integrated scientific effort to achieve these objectives.
The Division of Control of Tropical Diseases (CTD) was established in January 1990, by uniting previously separate control activities for the different diseases into one programme. Thus, support of control activities will be strengthened and coordination improved. The mandate of CTD is to develop at global, regional and country levels strategies for the control of tropical diseases. It collaborates closely with TDR and helps promote the use of research findings emanating from this programme. CTD evaluates, adapts and makes available to the countries concerned existing or newly-developed control technologies and collaborates in drawing up practicable, manageable and sustainable strategies. It also encourages each affected country to establish a comprehensive control programme suited to its individual requirements. CTD will concentrate its efforts on the countries in greatest need for controlling tropical diseases to improve their chances of development.
Human commitment and resources are the most important features of TDR and CTD. Human commitment and resources are required of the world, if tropical diseases are not to become the great neglected diseases of mankind . The aim of this report is to demonstrate why that commitment and those resources are so necessary.
Tore Godal Director, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases
Jose Najera Director, WHO Division of Control of Tropical Diseases
Malaria remains the most important of the tropical diseases - widespread throughout the tropics, but also occurring in many temperate regions. The disease exacts a heavy toll of illness and death - especially amongst children in endemic areas. It also poses a risk to business travellers, tourists and immigrants, and imported cases of malaria are increasingly seen in nonendemic areas such as Europe and North America. Epidemics are frequent in rural areas experiencing intense economic development. Treatment and control have become more difficult with the spread of drug resistant strains of malaria, and insecticide resistant strains of the mosquito vectors.
Causative agents: Single-celled protozoan parasites of the genus Plasmodium. Four species infect man:
P. falciparum - throughout tropical Africa, Asia and Latin America
P. vivax - worldwide in tropical and some temperate zones
P. ovale - mainly in tropical West Africa
P. malariae - worldwide but very patchy distribution
Estimated number of people infected: 267 million
Estimated number of clinical cases: 107 million per year
Estimated mortality: 1-2 million per year
Number of countries affected: 103
Number of people considered at risk: 2100 million
Transmission: Malaria parasites are inoculated by the bite of infected female mosquitos of the genus Anopneles (male mosquitos do not bite). The parasites multiply tremendously in the liver and in infected red blood cells. Vector mosquitos become infected by feeding on the blood of infected people, and the parasites then undergo another phase of reproduction in the infected mosquito.
Clinical symptoms: Malaria begins as a flu-like illness 8-30 days after the infected mosquito bite. Typical cycles of fever, shaking chills and drenching sweats may then develop. The periodicity of these cycles depends on the malaria species, coinciding with parasite multiplication and red blood cell destruction. Falciparum malaria may not show this cyclic pattern and can be fatal if untreated or if treated with insufficiently effective drugs (death may be due to parasitized red cells blocking the blood vessels supplying the brain---cerebral malaria---or damage to other vital organs).
In many parts of Africa, where malaria has long been highly endemic, people are infected so frequently that they develop a degree of acquired immunity, and may become asysmptomatic carriers of the infection. This is reflected in the estimated number of people infected (267 million) compared with the estimated number of clinical cases of malaria (107 million per year). Epidemics of clinical malaria are often associated with numbers of non-immune people moving to highly-endemic areas (eg. in search of work) where they quickly succumb to the infection.
Over the last few years, epidemics or atypical increases in malaria incidence have been reported from several areas, including the Amazon region, Ethiopia, Madagascar, Sri Lanka and the Solomon Islands.
Prevention and Treatment: (1) Avoid bites of anopheline mosquitos by wearing clothing which limits the amount of exposed skin, and through the use of repellents, mosquito nets, fumigant coils or insecticidal sprays. (2) When exposure is inevitable, use prophylactic drugs such as chloroquine or, in areas of high transmission of resistant falciparum parasites, mefloquine or doxycycline*. (3) Treat suspected or confirmed infections promptly. Quick treatment is of the utmost importance because life-threatening disease can develop within hours. Drugs effective against local parasite populations must be used; such drugs may include chloroquine, quinine, mefloquine, or halofantrine, depending on resistance patterns in the area where the infection was contracted.
In endemic areas, malaria control relies on diagnosis and prompt treatment of infected people, plus measures to reduce mosquito transmission of infections. Depending on local conditions, this may include spraying houses with residual insecticides, and modifying aquatic breeding sites to make them unsuitable for development of anopheline mosquito larvae.
[*note, several strains of Plasmodium are resistant to one or more antimalarial drugs. Thus no prophylactic drug can guarantee protection]
Control Priorities In Malaria
Research Priorities In Malaria
Epldemlology and Vector Control
Schistosomiasis is also known as bilharzia or bilharziasis after german pathologist Theodor Bilharz who first discovered the parasites in Egypt in 1851. The infection is wide spread with a relatively low mortality rate but very high morbidity rate-causing severe debilitating illness in millions of people. It is often associated with water development projects, such as dams and irrigations schemes, where the snail intermediate hosts of the parasite breed in water where people swim, wash and fish.
Causative agents: Trematode flatworms (flukes) of the genus Schistosoma, transmitted from infected snails.
S. mansoni-Africa and Latin America
S. haematobium-Africa and the Middle East
S. japonicum-SE Asia and parts of Western Pacific region (also S. intercalatum in small foci in Africa, and S. mekongi in the Mekong river basin of SE Asia)
Estimated number of cases: 200 million
Estimated mortality rate: <200 000/year
Number of people considered at risk: 500-600 million
Number of countries affected: 76
Transmission: In water, larval stages of schistosomes (known as cercaria) are shed from infected snails and penetrate the skin of people in the water. The snails become infected by another larval stage of the schistosome (known as miracidia) which hatch from eggs passed in the urine or stool of infected people. Schistosoma haematobium is mainly transmitted by Bulinus snails, S. mansoni by Biomphalaria, and S. japonicum by the amphibious Oncomelania.
Clinical symptoms: Adult male and female schistosomes live together in blood vessels of different organs; they release eggs--some of which are passed out in the urine (S. haematobiurn) or stools (S. mansoni, S. japonicum), but some eggs become lodged in the tissues. Reactions to schistosome eggs lodged in the tissues are the cause of disease in schistosomiasis.
In urinary schistosomiasis (due to S. haematobiurn), damage to the urinary tract is revealed by blood in the urine. Urination becomes painful and there is progressive damage to the bladder, ureters, and then to the kidneys. Bladder cancer is quite common in advanced cases.
Intestinal schistosomiasis (due to S. mansoni, S. japonicum or S. mekongi) is slower to develop. There is progressive enlargement of the liver and spleen as well as damage to the intestine, due to fibrotic lesions around the schistosome eggs lodged in these tissues and hypertension of the abdominal blood vessels. Repeated bleeding from these vessels leads to blood in the stools, and can be fatal.
Prevention: Avoid contact with streams and ponds where infected snails live. Never defecate or urinate in or near open waters, so that snails have less chance of becoming infected.
Treatment: Metrifonate (cheap, but requires 3 spaced doses, only effective against S. haematobiurn)
Oxamniquine (single dose, but only effective against S. mansoni)
Praziquantel - effective in a single dose against all species of schistosome
Control Priorities in Schistosomiasis
Research Priorities In Schistosomiasis
Biochemistry and Chemotherapy
Epidemiology and Snail Control
Filariasis affects the lives of a billion people, mainly in Africa, Asia and to a lesser extent in Latin America. The different types of filariasis are rarely life-threatening in themselves, but cause chronic suffering and disability. Lymphatic filariasis can lead to hugely swollen limbs (a condition known as elephantiasis) while onchocerciasis can lead to blindness.
Causative agents: Parasitic nematode worms of the family filariidae. Two types are of particular importance-onchocerciasis (also known as river blindness) due to Onchocerca volvulus transmitted by Simulium blackflies, and lymphatic filariasis (also known as elephantiasis) due to Wuchereria bancrofti, Brugia malayi or B. timori, which are transmitted by various species of mosquito. Wuchereria is mainly transmitted by Culex quinquefasciatus and some species of Anopheles, while Brugia is mainly transmitted by species of Mansonia mosquitos.
Transmission and Symptoms: Infective larvae of Wuchereria and Brugia are transmitted to man through the bite of infected mosquitos. They develop as adult worms (macrofilariae) in the afferent lymphatic vessels, causing severe inflammation of the lymphatic system. Adult Wuchereria are often lodged in the lymphatics of the spermatic cord, causing scrotal damage and swelling. Elephantiasis-painful disfiguring swelling of the limbs-is a classic sign of late-stage disease. The adult worms can live for many years, giving rise to large numbers of larval forms (microfilariae) which circulate in the lymphatics and blood where they can be taken up by appropriate species of blood-sucking mosquito.
In onchocerciasis, infective larvae are transmitted through the bite of infected Simulium blackflies. Adult worms develop in subcutaneous nodules, releasing large numbers of micro-filariae into the surrounding tissues. Most of the pathology of onchocerciasis results from the migration of microfilariae into the skin and eyes, leading to intense itching and disfiguring dermatitis, and ocular damage including blindness.
Prevention and Treatment: In much of West Africa, transmission of Onchocerca has been greatly reduced through the activities of the 11-nation Onchocerciasis Control Programme (OCP). This has mainly involved regular release of biodegradable insecticides into the rivers to destroy the Simulium larvae. More recently, a newly-developed microfilaricide ivermectin - has been introduced to treat infected people and halt the progression of disease.
Lymphatic filariasis has for many years been treated with diethylcarbamazine (DEC), but this drug is not always easy to administer and often has unpleasant side-effects. Ivermectin is now entering field trials against lymphatic filariasis in NE Brazil and parts of Africa, India, SE Asia and the Western Pacific region. Transmission of lymphatic filariasis can also be reduced by avoiding mosquito bites in endemic areas (eg. using repellents, bednets, insecticides) and, since important mosquito vectors such as Culex quinquefasciatus often breed in polluted urban waters (such as blocked drains and sewers), urban sanitation can make an important contribution to reducing the risk of this disease.
Control Priorities in Filariasis
Research Priorities in Filariasis
Epidemiology and Vector Control
African trypanosomiasis or sleeping sickness is a severe disease, often fatal if untreated, due to trypanosome parasites transmitted by tsetse flies. The disease occurs in scattered foci throughout the subsaharan tsetse belts of Africa-an area of some 10 million sq km. It is closely related to a wide spread cattle infection known as Nagana, which restricts cattle rearing in many areas of the continent. Although sleeping sickness claims relatively few lives today, the risk of severe epidemics means that surveillance and active control measures must be maintained throughout the endemic areas.
Causative agents: Protozoan parasites of the genus Trypanosoma, transmitted by tsetse flies. Trypanosoma brucei rhodesiense occurs mainly in East and southern Africa, with T.b. gambiense mainly in West and Central Africa. A third subspecies, T.b. brucei is responsible for the cattle disease, Nagana, but does not infect man.
Estimated number of cases: 25 000 per year
Number of countries affected: 36
Number of people at risk: 50 million
Transmission and Clinical Symptoms: Cattle and other large mammals are important reservoir hosts of trypanosomes. Tsetse flies can acquire a trypanosome infection by feeding on these infected animals--or on an infected person. The trypanosomes are then injected into the blood through the bite of an infected tsetse flies when it feeds again. The trypanosomes then multiply and invade most tissues.
In humans, infection with African trypanosomiasis leads initially to malaise, lassitude and irregular fevers. This is followed by a range of symptoms including headache, anaemia, joint pains and swollen tissues, progressing, as the parasites invade the central nervous system, to mental deterioration, coma and death. T.b. rhodesiense infection is usually acute, causing severe symptoms and death within a few days or weeks; gambiense infection tends to progress more slowly.
Prevention and Control: Control of African sleeping sickness relies mainly on systematic surveillance of the population at risk, and treatment of diagnosed cases. In addition, reduction of the tsetse fly vectors has an important role, especially against the rhodesiense form of the disease (and against the cattle disease, Nagana). In the past, this has involved extensive bush clearance to destroy the flies breeding and resting sites, and widespread use of insecticides. More recently, efficient traps have been developed, that can keep tsetse fly populations down to very low levels.
Treatment of African sleeping sickness has always been difficult, especially in the later stages of the disease (ie. with central nervous system involvement). Pentamidine is not effective against late-stage disease and some parasite strains are now resistant to it. Suramin must be administered intravenously and can have adverse side-effects. Melarsoprol--an arsenical drug developed in the 1940s--is used against late-stage disease (although some resistant strains have been reported) but melarsoprol often incurs serious side-effects--sometimes fatal. Very recently, a new drug originally developed as an anticancer agent--DFMO (also known as eflomithine)--has given very promising results in field trials against gambiense infection, but seems much less effective against the more virulent rhodesiense form.
Control priorities In African trypanosomiasis
Research Priorities In African Trypanosomiasis
Immunology and Pathology
Epidemiology and Vector Control
(also known as South American typanosomiasis)
Chagas disease, which occurs only in the New World, gets its name from Dr Carlos Chagas-a Brazilian doctor who first described the disease in 1909. Remarkably, he also worked out the parasite's life-cycle, and identified the insects that transmit it and some of the small mammals that can act as reservoir hosts. He also made major contributions to studying the nature of the disease and how to prevent its transmission. Regrettably, the disease remains incurable, although transmission can be successfully interrupted by control of the insect vectors in houses and peridomestic habitats.
Causative agent: a protozoan parasite called Trypanosoma cruzi, transmitted by blood-sucking 'assassin bugs' (subfamily Triatominae).
Estimated number of cases: 16-18 million
Number of countries affected: all of Central and South America (occasional cases in southern USA)
Number of people at risk: 90 million
Transmission: Trypanosoma cruzi is transmitted by large bloodsucking 'assassin bugs' of the subfamily Triatominae. These insects (similar to large bed bugs) commonly live in the cracks and crevices of poor-quality houses in most rural areas of Latin America. They emerge from their cracks at night to bite and suck blood from the sleeping occupants. However, the parasites are not transmitted in the bite of insect. Instead, they are deposited with the insect faeces onto the skin. Scratching the bites probably helps the parasites penetrate and enter the bloodstream.
T.cruzi can also be transmitted by blood transfusion from infected people-this is increasingly a problem in blood banks and hospitals in some areas.
Clinical symptoms: Often, there is is a small sore at the bite where the parasites entered the body. If this site is around the eye, that eyelid can develop a marked swelling (known as Romafla's sign). Within a few days, fever and swollen lymph nodes may develop, sometimes making the early stages of infection appear like malaria. This early acute phase of infection can be fatal, but more usually the patient survives to enter a symptomless phase which may last many months or years. During this period however, the parasites are invading most organs of the body, so that chronic symptoms eventually develop - often involving irreversible damage to heart and intestine. In such cases, the patient becomes progressively weaker, and may die from heart failure.
Prevention and control: For practical purposes, chronic Chagas disease is incurable (two drugs, nifurtimox and benznidazole, can be used for very early infections, but early diagnosis is difficult and adverse side-effects can occur). Moreover, because T. cruzi antigens may stimulate autoimmunity (immune attack on host tissues) the likelihood of a safe effective vaccine now seems very remote. Control therefore relies on insecticides to kill the triatomine bugs in houses, together with programmes of health education and low-cost housing improvements to render houses unsuitable for colonization by the bugs.
For the traveller, Chagas disease can be avoided by not sleeping in infested houses, and, if blood transfusion is required, using blood that has been treated with a blue dye (crystal violet) that eliminates the parasites from stored blood.
Control Priorities In Chagas disease
Research Priorities In Chagas disease
Epidemiology and Vector Control
Treatment and Patient Care
Leishmania parasites get their name from W.B. Leishman who developed in 1901 one of the earliest stains specific for this type of parasite. They are widespread in the New World and Old World (but not in SE Asia), and human infections are still found in many parts of Europe such as France, Italy, Greece, Malta, Spain, Portugal, Turkey and southern USSR. Although generally known for causing disfiguring lesions, epidemics of visceral forms of leishmaniasis have caused thousands of deaths.
Causative agents: Parasitic protozoa of the genus Leishmania, transmitted by infected sandflies. Several species and subspecies infect man, leading to symptoms ranging from simple self-healing skin ulcers (eg. due to Leishmania major) to severe life-threatening disease (eg. visceral leishmaniasis, known as Kala-azar, due to L. donovani).
Estimated number of cases: 12 million
Number of new cases per year: >400 000
Number of countries affected: 80
Number of people at risk: approx. 350 million
Transmission: Most forms of leishmaniasis are originally infections of small mammals (known as reservoir hosts) which play a major role in the epidemiology of this disease. Man becomes infected through the bite of infected sandflies subfamily phlebotominae)-tiny sand-coloured biting flies that breed in moist soil, for example in forest areas, caves, or in the burrows of small rodents. Old World forms of Leishmania are transmitted by sand flies of the genus Phlebotomus, while New World forms are mainly transmitted by sandflies of the genus Lutzomyia. The sand flies become infected by feeding from infected reservoir hosts or from infected people.
In the mammalian host, Leishmania parasites invade cells called macrophages, where they multiply to eventually rupture the cell and invade more macrophages.
Clinical symptoms: About 20 species and subspecies of Leishmania are known to infect man. Each causes a different range of symptoms. The most common infection, due to L. major in Africa and Asia, leads to one or more simple skin lesions (with local names such as 'Baghdadulcer', 'Delhiboil', 'boutond' orient). These generally heal after a few weeks or months to leave unsightly scars. In South America, mucocutaneous leishmaniasis (eg. due to L. braziliensis) also begins with simple skin ulcers, but these can spread to give hideous tissue destruction-especially of the nose and mouth. Visceral leishmaniasis (eg. Kala azar, due to L. donovam) is also a serious disease, usually fatal if untreated. Common symptoms include fever, malaise, weightloss, and then anaemia and swelling of spleen, liver and lymph nodes.
Prevention and treatment: Simple cutaneous leishmaniasis will usually heal without treatment, leaving the person immune to further infection with that species of Leishmania. Thus, in many parts of the Middle East, infections are deliberately encouraged on the buttocks of babies in order to immunize them against further infections (thus avoiding disfiguring scars on the face) . However, other forms of leishmaniasis are extremely difficult to treat, usually requiring a long course of pentavalent antimony drugs (Glucantime or Pentostam) and sometimes the antibiotic amphotericin B. Often however, infection can be prevented by avoiding sandfly bites (eg. using repellants or insecticides). Many forms of leishmaniasis are related to specific human activities that bring man directly into contact with sandflies. For example, cutaneous infections known as 'chiclero's ulcer' in Latin America is particularly associated with forest workers who encounter sandflies while collecting latex from chicle trees (to make chewing gum).
In some areas (such as the Mediterranean region, parts of the Soviet Union and China, and periurban districts of other reservoir hosts.
Control priorities in Leishmaniasis
--vector control by spraying houses with insecticides (especially for urban forms of leishmaniasis)
--destruction of infected reservoir hosts (especially small rodents in areas of cutaneous leishmaniasis and dogs visceral leishmaniasis
Research Priorities in Leishmaniasis
Epldemlology and Diagnosis
Leprosy is sometimes known as Hansens disease or Hanseniasis, after Norwegian physician Armauer Hansen who in 1873 first identified its cause. Because of its psychological and social effects, leprosy is referred to in many languages as "the big disease."
Causative agent: a slow-growing bacterium called Mycobacterium leprae (related to M. tuberculosis, the cause of TB)
Number of cases: 3.9 million officially registered cases in 1989 10-12 million estimated total
Number of countries affected: 121 with more than 100 registered cases
Number of people at risk: 1600 million resident in endemic areas
Transmission: Humans seem to be the only natural hosts of M. leprae*. The bacterium is believed to be transmitted mainly from the nasal discharge of infected people, but might also be transmitted by skin contact. In the body, the bacteria grow mainly in nerve cells and macrophage cells in the skin.
Clinical symptoms: The clinical course of leprosy varies from asymptomatic infections to severe disfiguring disease. Skin lesions may appear and heal spontaneously. As the disease progresses (usually over several years), the skin lesions may become more frequent. These lesions range from depigmented patches - usually with loss of skin sensitivity - to multiple nodules with extensive skin thickening and folding. Loss of sensitivity in the skin often results in unnoticed burns or ulcers. Lesions of the nerves can lead to muscle weakness and atrophy resulting in deformities, especially of the feet and hands.
Prevention and Treatment: For many years, the only drug available against leprosy was dapsone. This drug mainly acts by stopping the bacteria from multiplying, rather than killing them directly. Thus long courses of treatment were necessary - often life-long. Moreover, patients risked relapse, and dapsone resistant strains of leprosy were becoming widespread. With TDR support, much more effective multidrug treatment regimes have been developed, using combinations of dapsone with rifampicin and clofazimine. Other new drugs are under large-scale trials.
Over 2.6 million leprosy patients are now being treated - or have already completed treatment- with the multidrug therapy (MDT) regimes. Of these, 850 000 have already been cured by this treatment. Since 1987, the number of registered leprosy patients has been reduced from 5.8 million to 4.9 million in 1988 and 3.9 million in 1989.
Prevention of leprosy by vaccination is another goal. The tuberculosis vaccine, BCG, offers some protection, but more effective vaccines based on killed M. leprae together with BCG are now undergoing large-scale field trials in India, Malawi and Venezuela. Genetically engineered vaccines are also under development.
* The 9-banded armadillo can be infected experimentally, and thus provides a vital source of material for research and vaccine preparation.
Control Priorities In Leprosy
Research Priorities In Leprosy
* to better understand nerve damage in leprosy
For further information contact:
TDR Communications WHO 1211 Geneva 27 Switzerland Tel. (22)791-3811 791 -3810 791-3809 Fax (WHO): (22) 791-0746 (TDR): (22) 788-0839 Telex: 415416 Cable address: UNISANTE-GENEVA
WHO African Region I, II
WHO Eatern Mediterranean Region
WHO South-EAst Asian Region
WHO Western Pacific Region
WHO Redion of the AmericasI, II
WHO European Region I, II