Trypanosoma

1rypanosoma

Trypanosoma sp. among red blood cells.
Scientific classification
omain: Eukaryota
Kingdom: Excavata
Phylum: Euglenozoa
Class: Kinetoplastida
Order: Trypanosomatida
Genus: 1rypanosoma
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 ndia
[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. ts 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. ntracellular lifecycle stages are
normally found in the amastigote form. The trypomastigote morphology is unique to
species in the genus Trypanosoma.

frican trypanosomiasis (sleeping sickness)

act sheet N259
October 2010

ey facts
O $leeping sickness occurs only in 36 sub-$aharan AIrica countries where there are tsetse Ilies that can transmit the
disease.
O The people most exposed to the tsetse Ily and thereIore the disease are in rural populations dependent on agriculture,
Iishing, animal husbandry or hunting.
O Trypanosoma brucei gambiense (T.b.g.) accounts Ior 95 oI reported cases oI sleeping sickness.
O AIter continued control eIIorts, the number oI cases reported in 2009 has dropped below
10 000 Ior Iirst time in 50 years.
O iagnosis and treatment oI the disease is complex and requires speciIically skilled staII.

Definition of the disease

uman AIrican 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 Ily
(Glossinagenus) bites which have acquired their inIection Irom human beings or Irom animals harbouring the
human pathogenic parasites.
Tsetse Ilies are Iound just in sub-$aharan AIrica though only certain species transmit the disease. or reasons that
are so Iar unexplained, there are many regions where tsetse Ilies are Iound, but sleeping sickness is not. Rural
populations living in regions where transmission occurs and which depend on agriculture, Iishing, animal husbandry
or hunting are the most exposed to the tsetse Ily and thereIore to the disease. The disease develops in areas ranging
Irom a single village to an entire region. Within an inIected area, the intensity oI the disease can vary Irom one
village to the next.
orms of human African trypanosomiasis
uman AIrican trypanosomiasis takes two Iorms, depending on the parasite involved:
O Trypanosoma brucei gambiense (T.b.g.) is Iound in west and central AIrica. This Iorm currently accounts Ior over
95 oI reported cases oI sleeping sickness and causes a chronic inIection. A person can be inIected Ior months or
even years without major signs or symptoms oI the disease. When symptoms emerge, the patient is oIten already in
an advanced disease stage where the central nervous system is aIIected.
O Trypanosoma brucei rhodesiense (T.b.r.) is Iound in eastern and southern AIrica. Nowadays, this Iorm represents
under 5 oI reported cases and causes an acute inIection. irst signs and symptoms are observed a Iew months or
weeks aIter inIection. The disease develops rapidly and invades the central nervous system.
Another Iorm oI trypanosomiasis occurs mainly in 21 Latin American countries. It is known as American
trypanosomiasis or Chagas disease. The causal organism is a diIIerent species Irom those causing the AIrican Iorm
oI the disease.
Animal trypanosomiasis
Other parasite species and sub-species oI 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 inIected with T.b. gambiense and act as a reservoir. owever the
precise epidemiological role oI this reservoir is not yet well known. The disease in domestic animals, particularly
cattle, is a major obstacle to the economic development oI aIIected rural areas.
ajor human epidemics
There have been several epidemics in AIrica over the last century:
O one between 1896 and 1906, mostly in Uganda and the Congo Basin
O one in 1920 in a number oI AIrican countries and
O the most recent epidemic occurred in 1970.
The 1920 epidemic was controlled thanks to mobile teams which organized the screening oI millions oI people at
risk. By the mid 1960s, the disease had almost disappeared. AIter this success, surveillance was relaxed, and the
disease reappeared in several areas over the last 30 years. The eIIorts oI WO, national control programmes,
bilateral cooperation and nongovernmental organizations (NGOs) during the 1990's and the beginning oI the 21st
century stopped and reversed the upward trend oI new cases.
Distribution of the disease
$leeping sickness threatens millions oI people in 36 countries in sub-$aharan AIrica. Many oI the aIIected
populations live in remote areas with limited access to adequate health services, which hampers the surveillance and
thereIore the diagnosis and treatment oI cases. In addition, displacement oI populations, war and poverty are
important Iactors leading to increased transmission and this alters the distribution oI the disease due to weakened or
non-existent health systems.
O In 1986, it was estimated that some 70 million people lived in areas where disease transmission could take place.
O In 1998, almost 40 000 cases were reported, but estimates were that 300 000 cases were undiagnosed and thereIore
untreated.
O uring epidemic periods prevalence reached 50 in several villages in the emocratic Republic oI Congo, Angola
and $outhern $udan. $leeping sickness was the Iirst or second greatest cause oI mortality in those communities,
ahead oI even IV/AI$.
O By 2005, surveillance was reinIorced and the number oI new cases reported on the continent was reduced; between
1998 and 2004 the number oI both Iorms oI the disease Iell Irom
37 991 to 17 616. The estimated number oI actual cases was between 50 000 and 70 000.
O In 2009, aIter continued control eIIorts, the number oI cases reported has dropped below
10 000 (9878) Ior Iirst time in 50 years. The estimated number oI actual cases is currently
30 000.
In 2000 and 2001, WO established public-private partnerships with Aventis Pharma (now sanoIi-aventis) and
Bayer ealthCare which enabled the creation oI a WO surveillance team, providing support to endemic countries
in their control activities and the supply oI drugs Iree oI charge Ior the treatment oI patients.
In 2006, the partnership was renewed and the success in curbing the number oI sleeping sickness cases encouraged
other private partners to sustain the WO`s initial eIIort towards the elimination oI the disease as a public health
problem.
urrent situation in endemic countries
The prevalence oI the disease diIIers Irom one country to another as well as in diIIerent parts oI a single country.
O In the last 10 years, over 70 oI reported cases occurred in the emocratic Republic oI Congo (RC).
O In 2008 and 2009 only the RC and Central AIrican Republic declared over 1000 new cases per year.
O Angola, Chad, $udan and Uganda declared between 100 and 1000 new cases per year.
O Countries such as, Cameroon, Congo, Cte d'Ivoire, Equatorial Guinea, Gabon, Guinea, Kenya, Malawi, Nigeria,
United Republic oI Tanzania, Zambia and Zimbabwe are reporting Iewer than 100 new cases per year.
O Countries like Benin, Botswana, Burkina aso, Burundi, Ethiopia, Gambia, Ghana, Guinea Bissau, Liberia, Mali,
Mozambique, Namibia, Niger, Rwanda, $enegal, $ierra Leone, $waziland and Togo have not reported any new
cases Ior over a decade. Transmission oI the disease seems to have stopped but there are still some areas were it is
diIIicult to asses the exact situation because the unstable social circumstances and/or remote accessibility hinders
surveillance and diagnostic activities.
nfection and symptoms
The disease is mostly transmitted through the bite oI an inIected tsetse Ily but there are other ways in which people
are inIected with sleeping sickness.
O Mother-to-child inIection: the trypanosome can cross the placenta and inIect the Ietus.
O Mechanical transmission through other blood sucking insects is possible. owever, it is diIIicult to assess the
epidemiological impact oI transmission.
O Accidental inIections have occurred in laboratories due to pricks Irom contaminated needles.
In the Iirst stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph. This is known as a
haemolymphatic phase, which entails bouts oI Iever, headaches, joint pains and itching.
In the second stage the parasites cross the blood-brain barrier to inIect the central nervous system. This is known as
the neurological phase. In general this is when more obvious signs and symptoms oI the disease appear: changes oI
behaviour, conIusion, sensory disturbances and poor coordination. isturbance oI the sleep cycle, which gives the
disease its name, is an important Ieature oI the second stage oI the disease. Without treatment, sleeping sickness is
considered Iatal.
Disease management: diagnosis
isease management is made in three steps.
1. $creening Ior potential inIection. This involves using serological tests (only available Ior T.b.gambiense) and
checking Ior clinical signs - generally swollen cervical glands.
2. iagnosing whether the parasite is present.
3. $taging to determine the state oI disease progression. This entails examining cerebro-spinal Iluid obtained by lumbar
puncture and is used to determine the course oI treatment.
iagnosis must be made as early as possible and beIore the neurological stage in order to avoid complicated,
diIIicult and risky treatment procedures.
The long, relatively asymptomatic Iirst stage oI T. b. gambiense sleeping sickness is one oI the reasons why an
exhaustive, active screening oI the population at risk is required, in order to identiIy patients at an early stage and
reduce transmission. Exhaustive screenings require a major investment in human and material resources. In AIrica
such resources are oIten scarce, particularly in remote areas where the disease is mostly Iound. As a result, many
inIected individuals may die beIore they can ever be diagnosed and treated.
1reatment
The type oI treatment depends on the stage oI the disease. The drugs used in the Iirst stage oI the disease are oI
lower toxicity and easier to administer. The earlier the disease is identiIied, the better the prospect oI a cure.
Treatment success in the second stage depends on a drug that can cross the blood-brain barrier to reach the parasite.
$uch drugs are toxic and complicated to administer. our drugs are registered Ior the treatment oI sleeping sickness
and provided Iree oI charge to endemic countries.
irst stage treatment:
O !entamidine: discovered in 1941, used Ior the treatment oI the Iirst stage oIT.b. gambiense sleeping sickness.
espite non-negligible undesirable eIIects, it is in general well tolerated by patients.
O Suramin: discovered in 1921, used Ior the treatment oI the Iirst stage oI T.b. rhodesiense. It provokes certain
undesirable eIIects, in the urinary tract and allergic reactions.
$econd stage treatment:
O elarsoprol: discovered in 1949, it is used in both Iorms oI inIection. It is derived Irom arsenic and has many
undesirable side eIIects. The most dramatic is reactive encephalopathy (encephalopathic syndrome) which can be
Iatal (3 to 10). An increase in resistance to the drug has been observed in several Ioci particularly in central
AIrica.
O flornithine: this molecule, less toxic than melarsoprol, was registered in 1990. It is only eIIective against T.b.
gambiense. The regimen is strict and diIIicult to apply.
O A combination treatment oI nifurtimox and eflornithine has been recently introduced (2009). It simpliIies the use
oI eIlornithine in monotherapy, but unIortunately it is not eIIective Ior T.b. rhodesiense. NiIurtimox is registered Ior
the treatment oI American trypanosomiasis but not Ior human AIrican trypanosomiasis. Nevertheless, aIter saIety
and eIIicacy data provided by clinical trials, its use in combination with eIlornithine has been accepted and included
in the WO List oI Essential Medicine, and it is provided Iree oI charge Ior this purpose by WO.
response
WO provides support and technical assistance to national control programmes. An important part oI the response
is a WO private partnership with sanoIi-aventis (pentamidine, melarsoprol and eIlornithine) and Bayer AG
(suramin and niIurtimox) to provide the drugs Iree oI charge to endemic countries. A network has been established
Ior donor countries, private Ioundations, 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 oI the WO Programme are to:
O strengthen and coordinate control measures and ensure Iield activities are sustained;
O strengthen existing surveillance systems;
O ensure accessibility to diagnostic and treatment;
O support the monitoring oI treatment and drug resistance throughout the network;
O develop inIormation database and epidemiological analysis oI data;
O implement training activities;
O support operational research to improve treatment and diagnostic tools;
O promote collaboration with the ood and Agriculture Organization (AO) in charge oI animal trypanosomiasis and
the International Atomic Energy Agency (IAEA) dealing with vector control through male Ilies made sterile by
radiation. The three UN agencies along with the AIrican Union have promoted the Programme Against AIrican
Trypanosomiasis (PAAT);
O coordinate and synergize vector control activities lead by the Pan AIrican Tsetste and Trypanosomosis Eradication
Campaign oI the AIrica Union.
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