Trypanosoma

Trypanosoma

Trypanosoma sp. among red blood cells.

Scientific classification

Domain: Eukaryota

Kingdom: Excavata

Phylum: Euglenozoa

Class: Kinetoplastida

Order: Trypanosomatida

Genus: Trypanosoma
Gruby, 1843

This article is about the genus Trypanosoma, for the specific human pathogens
Trypanosoma is a genus of kinetoplastids (class Kinetoplastida), a monophyletic group
of unicellular parasitic flagellate protozoa. The name is derived from
the Greek trypano (borer) andsoma (body) because of their corkscrew-like motion. All
trypanosomes are heteroxenous (requiring more than one obligatory host to complete
life cycle) and are transmitted via a vector. The majority of species are transmitted by
blood-feeding invertebrates, but there are different mechanisms among the varying
species. Then in the invertebrate host they are generally found in the intestineand
normally occupy the bloodstream or an intracellular environment in the mammalian host.

Trypanosomes infect a variety of hosts and cause various diseases, including the fatal
human diseases sleeping sickness, caused by Trypanosoma brucei, and Chagas
disease, caused byTrypanosoma cruzi.

The mitochondrial genome of the Trypanosoma, as well as of other kinetoplastids,

known as thekinetoplast, is made up of a highly complex series of catenated circles and
minicircles and requires a cohort of proteins for organisation during cell division.

Selected species
Species of Trypanosoma include the following:

 T. ambystomae in amphibians
 T. antiquus Extinct (Fossil in Eocene amber)
 T. avium, which causes trypanosomiasis in birds
 T. boissoni, in elasmobranch
 T. brucei, which causes sleeping sickness in humans and nagana in cattle
 T. cruzi, which causes Chagas disease in humans
 T. congolense, which causes nagana in ruminant livestock, horses and a wide range
of wildlife
 T. equinum, in South American horses, transmitted via Tabanidae,
 T. equiperdum, which causes dourine or covering sickness in horses and
other Equidae
 T. evansi, which causes one form of the disease surra in certain animals (a single
case report of human infection in 2005 in India[2] was successfully treated
with suramin[3])
 T. everetti, in birds
 T. hosei in amphibians
 T. levisi, in rats
 T. melophagium, in sheep, transmitted via Melophagus ovinus
 T. paddae, in birds
 T. parroti, in amphibians
 T. percae, in the species Perca fluviatilis
 T. rangeli, believed to be nonpathogenic to humans
  T. rotatorium, in amphibians
 T. rugosae, in amphibians
 T. sergenti, in amphibians
 T. simiae, which causes nagana in pigs. Its main reservoirs are warthogs and bush
pigs
 T. sinipercae, in fishes
 T. suis, which causes a different form of surra
 T. theileri, a large trypanosome infecting ruminants
 T. triglae, in marine teleosts
 T. vivax, which causes the disease nagana, mainly in West Africa, although it has
spread to South America

 Hosts, life cycle and morphologies

The six main morphologies of trypanosomatids.

As trypanosomes progress through their life cycle they undergo a series of

morphological changes as is typical of trypanosomatids. The life cycle often consists of
the trypomastigote form in the vertibrate host and the trypomastigote
or promastigote form in the gut of the invertebrate host. Intracellular lifecycle stages are
normally found in the amastigote form. The trypomastigote morphology is unique to
species in the genus Trypanosoma.
 African trypanosomiasis (sleeping sickness)
Fact sheet N°259
October 2010

Key facts
 Sleeping sickness occurs only in 36 sub-Saharan Africa countries where there are tsetse flies that can transmit the
disease.
 The people most exposed to the tsetse fly and therefore the disease are in rural populations dependent on agriculture,
fishing, animal husbandry or hunting.
 Trypanosoma brucei gambiense (T.b.g.) accounts for 95% of reported cases of sleeping sickness.
 After continued control efforts, the number of cases reported in 2009 has dropped below
10 000 for first time in 50 years.
 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. The parasites
concerned are protozoa belonging to theTrypanosoma genus. They are transmitted to humans by tsetse fly
(Glossinagenus) 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 (T.b.g.) is found in west and central Africa. This form currently accounts for over
95% 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 symptoms emerge, the patient is often already in
an advanced disease stage where the central nervous system is affected.
 Trypanosoma brucei rhodesiense (T.b.r.) is found in eastern and southern Africa. Nowadays, this form represents
under 5% 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.
Another form of trypanosomiasis occurs mainly in 21 Latin American countries. It is known as American
trypanosomiasis or Chagas disease. The causal organism is a different species from those causing the African form
of the disease.
Animal trypanosomiasis
Other parasite species and sub-species of the Trypanosoma genus are pathogenic to animals and cause animal
trypanosomiasis in wild and domestic animal species. In cattle the disease is called Nagana, a Zulu word meaning
"to be depressed".
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 this reservoir 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.
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 had almost disappeared. After this success, surveillance was relaxed, and the
disease reappeared in several areas over the last 30 years. The efforts of WHO, national control programmes,
bilateral cooperation and nongovernmental organizations (NGOs) during the 1990's and the beginning of the 21st
century stopped and reversed the upward trend of new cases.
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 hampers the surveillance and
therefore the diagnosis and treatment of cases. In addition, displacement of populations, war and poverty are
important factors leading to increased transmission and this alters the distribution of the disease due to weakened or
non-existent health systems.
 In 1986, it was estimated that some 70 million people lived in areas where disease transmission could take place.
 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 Democratic Republic of Congo, Angola
and Southern Sudan. Sleeping sickness was the first or second greatest cause of mortality in those communities,
ahead of even HIV/AIDS.
 By 2005, surveillance was reinforced and the number of new cases reported on the continent was reduced; between
1998 and 2004 the number of both forms of the disease fell from
37 991 to 17 616. The estimated number of actual cases was between 50 000 and 70 000.
 In 2009, after continued control efforts, the number of cases reported has dropped below
10 000 (9878) for first time in 50 years. The estimated number of actual cases is currently
30 000.
In 2000 and 2001, WHO established public-private partnerships with Aventis Pharma (now sanofi-aventis) and
Bayer HealthCare which enabled the creation of a WHO surveillance team, providing support to endemic countries
in their control activities and the supply of drugs free of charge for the treatment of patients.
In 2006, the partnership was renewed and the success in curbing the number of sleeping sickness cases encouraged
other private partners to sustain the WHO’s initial effort towards the elimination of the disease as a public health
problem.
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).
 In 2008 and 2009 only the DRC and Central African Republic declared over 1000 new cases per year.
 Angola, Chad, Sudan and Uganda declared between 100 and 1000 new cases per year.
 Countries such as, Cameroon, Congo, Côte d'Ivoire, Equatorial Guinea, Gabon, Guinea, Kenya, Malawi, Nigeria,
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, Ghana, 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 were it is
difficult to asses 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
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 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.
Disease management: diagnosis
Disease management is made in three steps.
1. Screening for potential infection. This involves using serological tests (only available for T.b.gambiense) and
checking for clinical signs - generally swollen cervical glands.
2. Diagnosing whether the parasite is present.
3. Staging to determine the state of disease progression. This entails examining cerebro-spinal fluid obtained by lumbar
puncture and is used to determine the course of treatment.
Diagnosis must be made as early as possible and before the neurological stage in order to avoid 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 required, 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, many
infected individuals may die before they can ever be diagnosed and treated.
Treatment
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
and provided free of charge to endemic countries.
First stage treatment:
 Pentamidine: discovered in 1941, used for the treatment of the first stage ofT.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 has been recently introduced (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.
WHO response
WHO provides support and technical assistance to national control programmes. An important part of the response
is a WHO private partnership with sanofi-aventis (pentamidine, melarsoprol and eflornithine) and Bayer AG
(suramin and nifurtimox) to provide the drugs free of charge to endemic countries. A network has been established
for donor countries, private foundations, NGOs, regional institutions, research centres and universities to participate
in surveillance and control, and to undertake research projects to develop new drugs and diagnostic tools.
The objectives of the WHO Programme are to:
 strengthen and coordinate control measures and ensure field activities are sustained;
 strengthen existing surveillance systems;
 ensure accessibility to diagnostic and treatment;
 support the monitoring of treatment and drug resistance throughout the network;
 develop information database and epidemiological analysis of data;
 implement training activities;
 support operational research to improve treatment and diagnostic tools;
 promote collaboration with the Food and Agriculture Organization (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 three UN agencies along with the African Union have promoted the Programme Against African
Trypanosomiasis (PAAT);
 coordinate and synergize vector control activities lead by the Pan African Tsetste and Trypanosomosis Eradication
Campaign of the Africa Union.
For more information contact:
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