Three of a kind

The history and legacy of the tritryp parasites
Introducing the parasites that cause sleeping sickness, Chagas' disease and leishmaniasis.

Sometime between 1375 and 1406 – probably in Cairo – news of the terminal illness and death of the corrupt despotic Emperor Mari Jata of Mali reached the great Arab historian Ibn Khaldun:

"Jata had been smitten by the sleeping illness, a disease which frequently afflicts the inhabitants of that climate… Those afflicted are virtually never awake or alert. This sickness harms the patient and continues until he perishes…The illness persisted in Jata's humour for a duration of two years after which he died."

Jata's illness is characteristic of African trypanosomiasis, a disease that affects 36 African countries. Some 60 million people are thought to be at risk; about half a million cases of sleeping sickness arise each year, killing 66 000 people and disabling 100 000.

Sleeping sickness is caused by a single-celled parasite, Trypanosoma brucei, a distant relative of the malaria parasite. A different species of trypanosome, Trypanosoma cruzi, blights Central and South America, causing Chagas' disease. A third parasite, Leishmania, brings misery to millions across much of the Southern Hemisphere and parts of the Northern Hemisphere. Collectively, they are known as the 'tritryps'. Researchers hope that the newly completed genome sequences of the parasites will stimulate a wave of research and discovery that can lead to new ways of treating and preventing these pernicious diseases.

The three related parasites are members of a wider group of parasites called the kinetoplastids [named after a strange internal structure, the kinetoplast (see United front), and notable for their powerful flagella]. They are transmitted by blood-sucking insects.

African trypanosomiasis

The principal scourge of Africa is Trypanosoma brucei. It consists of three subspecies, two of which infect humans. T. brucei rhodesiense is found in East and Southern Africa, T. brucei gambiense in West and Central Africa, and both species in Uganda. T. brucei brucei is not infectious to humans, but in cattle it causes a wasting disease called nagana.

The parasites are transmitted in the saliva of blood-sucking female tsetse flies, found in Africa in a belt that stretches south of the Sahara and north of the Kalahari. The parasites proliferate at the site of the fly's bite, then spread into the lymph and bloodstream. The circulatory stages of the disease are characterised by lethargy, headache and fever.

Infections with T. b. rhodesiense tend to be more acute, the parasites taking only a few weeks to invade the internal organs, including the central nervous system, while T. b. gambiense is more insidious, taking several months or years. As the disease progresses, headache becomes severe, sleep becomes disrupted, personality can change and mental functions become impaired. Without treatment, infection with either form is fatal: damage to the central nervous system ends in coma and death.

In the bloodstream, the parasites can be attacked by the human immune system. They get round this through a process known as antigenic variation. They possess a thick surface coat of densely packed glycoproteins, which protects them against initial attack. The immune system follows up with specific antibodies, its heavy hitters. The antibodies kill most parasites, but by the time they have appeared, some of the parasites have switched coats and escape the body's onslaught (see Tackling tritryps).

Few effective drugs are available, so prevention is a priority. In Africa, mass treatment campaigns in the mid-20th century were very effective in cutting transmission of T. b. gambiense, as was the brute-force clearance of bush to destroy tsetse fly breeding and resting sites and the widespread use of insecticides. Neglected after the 1960s, T. brucei has returned, in an epidemic that has so far lasted 30 years.

These days, more sophisticated traps and screens can keep tsetse fly populations at low levels, while Zanzibar used the unusual approach of releasing sterile male tsetse flies, encouraging female flies to mate unproductively – a strategy that led to the elimination of Glossina austeni from the island.

Chagas' disease

In 1839, the young naturalist Charles Darwin wrote an account of triatomine bugs in Argentina:

"At night I experienced an attack (for it deserves no lesser name) of the benchuca, a species of Reduvius, the great black bug of the Pampas. It is most disgusting to feel soft, wingless insects, about an inch long, crawling over one's body. Before sucking they are quite thin, but afterwards they become round and bloated with blood, and in this state are easily crushed."

These triatomine bugs – also known as reduvids, assassin or kissing bugs – transmit the parasite Trypanosoma cruzi, the cause of Chagas' disease (also known as New World trypanosomiasis). Across South and Central America and Mexico, about 16–18 million people are thought to be infected.

The bugs infest cracks, crevices and roofs, and drop onto sleeping victims to gorge themselves with blood. They do not inject parasites directly while feeding: their bite is painless (hence the name kissing bugs) but their salivary secretions are itchy and, in order to make room for their dinner, the bugs defecate on the skin. The bitten rubs the faeces, full of parasites, into the bite wound.

Once in the body, the parasite invades a variety of cells, replicating and developing. Infected cells die and release the parasites, some of which remain as a bloodstream form – ready to be picked up by another blood-feeding bug. An initial acute phase of fever and swollen lymph nodes may cause illness and death, especially in young children, but usually ends when the immune system manages to reduce the number of parasites in the bloodstream.

Most patients then enter a long phase without symptoms during which time parasites are invading most organs of the body, often causing damage to the heart, intestines and oesophagus. In about 30 per cent of cases, fatal damage to the heart and digestive tract occurs during this chronic phase, often 10–25 years after the initial infection.

Insecticide spraying to kill the bugs has proved an effective method of control, as has improved housing and blood screening to prevent transmission through transfusions. The Southern Cone Initiative (involving Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay) began in the early 1990s and has cut the incidence of disease by 70 per cent, and similar initiatives have been launched in Andean countries in 1997 and Central America in 1998.

Leishmaniasis

Leishmaniasis covers a range of diseases caused by different species of Leishmania parasites. Ranging from mild, self-curing skin lesions, to a severe and debilitating visceral disease that is always fatal unless treated, leishmaniasis is endemic in 88 tropical and subtropical countries on four continents.

The parasites are transmitted by sand flies, being delivered when the fly takes a blood meal. White blood cells – macrophages – are mobilised against the infection, and engulf the parasites. But instead of being destroyed, the parasite actually thrives inside the macrophage.

At least 15 species of Leishmania infect people and although they look the same under the microscope, they can have markedly different effects on the body. Leishmania major, for example, is one of several species that cause a skin form or cutaneous leishmaniasis, whose common names include 'Oriental sore', 'Baghdad boil' and 'chiclero's ulcer', depending on species and geographical location. As localised infections at the site of the fly's bite wound, these mild skin lesions cure themselves in weeks or months, but lead to disfigurement and distress for millions of people.

The most serious form of the disease, visceral leishmaniasis, is caused by L. donovani, L. infantum and L. chagasi. One of the names for this disease, kala azar (the 'black sickness'), is a chilling reminder that when the parasite travels deeper into the body, invading cells in the spleen, bone marrow and liver, it can be fatal if untreated.

	Sleeping sickness	Chagas’ disease	Leishmaniasis
Caused by…	Trypanosoma brucei	Trypanosoma cruzi	Leishmania species
Where in the world?	36 countries in sub-Saharan Africa	18 countries in South America, Central America and Mexico	88 countries on 4 continents
Transmitted by	Tsetse fly	‘Kissing’ (triatomine) bugs	Sand flies
Global status	60 million people at risk. Every year, 300–500 000 new cases, 66 000 people die and 100 000 are disabled	120 million people at risk and 16–18 million infected. Every year, 300 000 new cases and 21 000 deaths	(Not counting epidemics) 350 million people at risk and 12 million infected. Every year, 1.5 million new cases of cutaneous leishmaniasis, 500 000 of visceral leishmaniasis, and 57 000 deaths
Reservoir animals (other than humans)	Cattle and other wild mammals	Cattle, pigs, rodents, dogs, armadillos and others	Dogs, foxes, rodents, sloths, anteaters, marsupials and hydraxes

David Bruce (1855–1931)

In the closing years of the 19th century, the people of Zululand were facing disaster. Their livelihood, which depended on their cattle, was in jeopardy: a fatal, wasting disease, which they called nagana, was decimating their herds. Surgeon Captain David Bruce was asked to investigate, arriving in Zululand in 1894 and initially using the veranda of his hut as a laboratory. Meanwhile, many of the horses of Europeans hunting game animals were dying, poisoned, they believed, by the deadly bite of the tsetse fly.

Bruce examined the blood of nagana cattle and saw: “a rapidly moving object…lashing about among the red blood corpuscles.” After consulting books in Natal, “it soon became evident that the rapidly vibrating object was probably a trypanosome”.

Trypanosomes had been seen in the blood of various animals from the middle of the century, their name being coined in 1843 by David Gruby in Paris: the motion of the mobile organism he saw in the blood of a frog reminded him of the action of a corkscrew.

When injected into horses and dogs, the blood from infected cattle caused symptoms similar to nagana. Bruce then sent oxen and dogs into the ‘fly belt’; after a few weeks he found in their blood the same trypanosome as in nagana cattle. Bruce went on to show that the trypanosomes living in the blood of healthy game animals are the source of the disease when transmitted to domestic animals by the tsetse fly.

In 1899, the trypanosome was given the name Trypanosoma brucei. In the early years of the 20th century, its human-infecting relatives were identified and linked to sleeping sickness.

Carlos Chagas (1879–1934)

The Brazilian Carlos Chagas rightfully lends his name to the disease caused by Trypanosoma cruzi. Between 1907 and 1909 he not only discovered the organism in its first known triatomine vector, but he also described the human disease and later realised the crucial role of wild mammals in the spread of the parasite.

In 1907, Chagas was working on an antimalaria campaign when he started investigating an insect “which inhabits human dwellings, attacking man at night, after the lights are out, and hiding during the day in the cracks of the walls.” In the hindguts of some bugs, he “confirmed there the presence of numerous flagellates”. Immediately supposing that the blood-sucking bugs might transmit a parasite to humans and other vertebrates, he found that many species of mammals could be infected with the parasite and, later, that the blood of a seriously ill child contained the new trypanosome – which he named after his mentor and friend, Oswaldo Cruzi.

Image: tsetse fly, courtesy of the Wellcome Trust Medical Photographic Library.

Three of a kind

African trypanosomiasis

Chagas' disease

Leishmaniasis

Related links