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West African Trypanosomiasis

Sleeping Sickness

West African trypanosomiasis (WAT) is an infectious disease caused by Trypanosoma brucei gambiense (T. brucei gambiense), for whom tsetse flies distributed in Central and West Africa serve as vectors. Infections outside endemic areas have not been described. Progressive weakness, somnolence, and neurological deterioration are the main clinical findings. The disease is relatively easily diagnosed and treated with a high-cure rate, so awareness is the limiting factor in industrialized nations. The World Health Organization aims at globally eradicating WAT by 2030. Of note, WAT is also referred to as chronic trypanosomiasis or Gambian sleeping sickness.


Presentation

An indurated, painful chancre at the site of inoculation may be the first symptom of WAT, but dermatological findings are not described in all cases [1]. Swelling of the tissue surrounding the insect bite may be attributed to the local replication of parasites and an early immune response. After a prolonged incubation period of weeks to months, patients start suffering from intermittent fever and chills. Febrile episodes typically last for a few days and occur at intervals of several weeks. At the same time, patients may develop lymphadenopathy. Posterior cervical lymphadenopathy is most commonly observed and referred to as Winterbottom's sign, a sign of West and East African trypanosomiasis [2].

General weakness and lethargy are other hallmarks of WAT and increase during the course of the disease, hence the name sleeping sickness. The fatigue of WAT patients is at least partially induced by anemia, and severely anemic patients tend to appear pale. Additionally, they may experience headaches, myalgia, and arthralgia. An evanescent, papuloerythematous rash and pruritus are also common [1].

As the disease progresses, patients enter the so-called meningo-encephalitic stage, and cognitive decline becomes apparent. Mental deficits may be associated with physical decay, but neurological symptoms typically dominate the clinical picture. Family members frequently describe personality changes. WAT patients suffer from confusion and memory impairment, sleepiness during daytime, and insomnia at night. Motor deficits may be present and may manifest in abnormal movements, gait disturbance, tremor, or incontinence, among others [2].

Magnetic resonance imaging of the brain may reveal diffuse hyperintensity of the white matter [2].

Fever
  • During this stage, patients experience headaches, joint pain, and fever. If untreated, the parasite next enters the central nervous system (CNS).[news-medical.net]
  • Additional symptoms may not develop until months or even years later, when affected individuals suffer from intermittent fever and swollen cervical lymph nodes.[symptoma.com]
  • MELLÉKLETBEN TALÁLHATÓ LISTÁHOZ en concerning animal health control measures relating to African swine fever in certain Member States and repealing Implementing Decision 2014/178/EU hu Azt hiszed, én élvezem, hogy az egész napomat egy tizenkilenc éves[hu.glosbe.com]
  • Infected persons may develop fever, headache, muscle pain and enlarged lymph nodes in the first stage.[infontd.org]
Fatigue
  • General weakness and fatigue increasingly affect the patient's quality of life, which is why WAT is also referred to as Gambian sleeping sickness.[symptoma.com]
Collapse
  • Interestingly, WAT had almost been eradicated in the 1960s, but a collapse of surveillance and control activities in most endemic countries, often exacerbated by civil conflicts, led to its reemergence.[symptoma.com]
Aspiration
  • Only patients in whom trypanosomes had been confirmed in blood or lymph aspirates were considered to be true positives.[scielosp.org]
  • The aspiration of swollen lymph nodes should be considered if parasites cannot be detected in peripheral blood, because lymphatic fluid generally contains large quantities of trypanosomes.[symptoma.com]
Arthralgia
  • Additionally, they may experience headaches, myalgia, and arthralgia. An evanescent, papuloerythematous rash and pruritus are also common.[symptoma.com]
Myalgia
  • Additionally, they may experience headaches, myalgia, and arthralgia. An evanescent, papuloerythematous rash and pruritus are also common.[symptoma.com]
Pruritus
  • An evanescent, papuloerythematous rash and pruritus are also common. As the disease progresses, patients enter the so-called meningo-encephalitic stage, and cognitive decline becomes apparent.[symptoma.com]
Chancre
  • An indurated, painful chancre at the site of inoculation may be the first symptom of WAT, but dermatological findings are not described in all cases.[symptoma.com]
Chancre
  • An indurated, painful chancre at the site of inoculation may be the first symptom of WAT, but dermatological findings are not described in all cases.[symptoma.com]
Incontinence
  • A 67-year-old Caucasian man presented with a 10-month history of cognitive deterioration, ataxic gait, somnolence and urinary incontinence. His symptoms had progressed more rapidly over the course of a month prior to admission.[ncbi.nlm.nih.gov]
  • Motor deficits may be present and may manifest in abnormal movements, gait disturbance, tremor, or incontinence, among others. Magnetic resonance imaging of the brain may reveal diffuse hyperintensity of the white matter.[symptoma.com]
Urinary Incontinence
  • A 67-year-old Caucasian man presented with a 10-month history of cognitive deterioration, ataxic gait, somnolence and urinary incontinence. His symptoms had progressed more rapidly over the course of a month prior to admission.[ncbi.nlm.nih.gov]
Headache
  • During this stage, patients experience headaches, joint pain, and fever. If untreated, the parasite next enters the central nervous system (CNS).[news-medical.net]
  • Additionally, they may experience headaches, myalgia, and arthralgia. An evanescent, papuloerythematous rash and pruritus are also common.[symptoma.com]
  • Infected persons may develop fever, headache, muscle pain and enlarged lymph nodes in the first stage.[infontd.org]
Personality Change
  • Family members frequently describe personality changes. WAT patients suffer from confusion and memory impairment, sleepiness during daytime, and insomnia at night.[symptoma.com]
  • Without diagnosis and treatment in the first phase, the disease progresses to the second stage where mental deterioration (i.e. personality changes, daytime sleepiness, progressive confusion), partial paralysis, balance problems, and eventually death[infontd.org]
Somnolence
  • Abstract West-African trypanosomiasis caused by Trypanosoma brucei gambiense is a rare imported infection presenting with somnolence, lymphadenopathy and wide-ranging neurological symptoms.[ncbi.nlm.nih.gov]
  • Progressive weakness, somnolence, and neurological deterioration are the main clinical findings. The disease is relatively easily diagnosed and treated with a high-cure rate, so awareness is the limiting factor in industrialized nations.[symptoma.com]
Insomnia
  • WAT patients suffer from confusion and memory impairment, sleepiness during daytime, and insomnia at night. Motor deficits may be present and may manifest in abnormal movements, gait disturbance, tremor, or incontinence, among others.[symptoma.com]
Memory Impairment
  • Then, patients may experience cognitive decline, confusion, memory impairment, motor deficits, and personality changes, among others. If left untreated, WAT leads to coma and death.[symptoma.com]

Workup

In endemic areas, clinical findings warrant a tentative diagnosis of WAT. Outside Central and West Africa, though, it's the patient's history of travel that causes their physicians to consider tropical infectious diseases as differential diagnoses. In the absence of anamnestic data indicating a recent stay in rural areas of Africa, WAT is highly unlikely.

Upon clinical suspicion, blood samples should be analyzed. Standard laboratory analyses may reveal anemia, thrombocytopenia, raised erythrocyte sedimentation rate, increased levels of C-reactive protein, hyperglobulinemia, and hypoalbuminemia [2]. Even though these findings suggest an infectious disease, they are non-specific. It's the microscopic examination of peripheral blood smears that allows for the visualization of trypanosomes. The aspiration of swollen lymph nodes should be considered if parasites cannot be detected in peripheral blood, because lymphatic fluid generally contains large quantities of trypanosomes.

Serological studies constitute a sensitive alternative to the direct proof of pathogens, and they allow for a distinction between West and East African trypanosomiasis. Furthermore, parasitemia diminishes during the chronic phase of the disease, but antibodies remain detectable. Wherever available, the presence of antibodies may be proven by immunofluorescent antibody test or enzyme-linked immunosorbent assay. In endemic areas, the rapid card agglutination test is preferred over other techniques. For samples to be analyzed with the rapid card agglutination test, they need to be cooled, and tests are run on an electrical device. In high-risk areas, cooling facilities and electricity may not be available, so more easily applicable rapid diagnostic tests are currently developed. They would allow for reliable diagnoses, even if technicians received little training [3]. Molecular biological studies may also be carried out to identify the etiological agent [4].

In case of positive results, samples of cerebrospinal fluid should be obtained to assess for progression to the meningo-encephalitic stage and involvement of the central nervous system. White blood cell counts exceeding 5/µl are generally interpreted as a sign of advanced-stage WAT [1] [5].

Treatment

WAT is a curable disease. Pentamidine, suramin, or diminazene may be administered to those who are diagnosed during the early, haemolymphatic stage of WAT. Since they these drugs are unable to cross the blood-brain-barrier, they are ineffective in the meningo-encephalitic stage of WAT [1] [6] [7]. Here, difluoromethylornithine, a selective and irreversible inhibitor of ornithine decarboxylase better known as eflornithine, is indicated. It is administered four times a day at a dose of 100 mg/kg. Cure is achieved in 95% of all cases where the patient is treated with eflornithine for two weeks. Alternatively, eflornithine may be combined with nifurtimox and administered for seven days. This regimen is associated with less toxicity [2]. In general, eflornithine is better tolerated than melarsoprol, an effective, yet more toxic drug able to cure advanced-stage WAT [6].

Prognosis

If WAT treatment is initiated in a timely manner, long-term sequelae due to central nervous system involvement may be avoided. If therapy is delayed until the meningo-encephalitic stage, complete recovery cannot be guaranteed, even though alertness, cognition, memory, and motor skills are likely to improve under therapy [2]. If left untreated, WAT runs a fatal course. Years may pass until the disease progresses to coma and death, which usually follows aspiration pneumonia.

Etiology

T. brucei gambiense are extracellular parasites. In mammalian hosts, they replicate by longitudinal division. The ingestion of the mammal's blood by arthropod vectors, namely by tsetse flies belonging to the species of Glossina palpalis and, in a minor scale, Glossina fuscipes and Glossina tachinoides, allows for trypanosomes to pass to their intermediate hosts. They eventually reach the midgut and salivary glands, where they continue to replicate. In the insect, they go through distinct phases of development until reaching the stage of metacyclic trypomastigotes. The latter are infective and may be transferred to a new mammalian host, usually a human being, when the fly takes another blood meal.

In men, trypanosomes initially replicate at the site of the insect bite. Within about a week, the parasites start to disseminate in the individual's body fluids. They can now be detected microscopically in blood samples. Large quantities of T. brucei gambiense can also be found in lymph nodes, which is why patients develop lymphadenopathy. Besides blood and lymph, the parasites may eventually reach the cerebrospinal fluid.

Beyond the direct transmission by infected flies, T. brucei gambiense may be transmitted vertically from a pregnant mother to her child [8] [9]. WAT could probably be transmitted through the transfusion of donated blood, but such cases are very rare.

Epidemiology

WAT accounts for the majority of cases of African trypanosomiasis, with about 97% of cases being caused by T. brucei gambiense [9]. Over the past decade, the disease' incidence has been decreasing, with <4,000 cases being reported in recent years. Most likely, though, WAT is underdiagnosed. The majority of cases occurs in the very poor regions of the Democratic Republic of Congo and the Central African Republic, where large parts of the population have limited access to medical care.

Because the etiological agent exhibits marked vector specificity and relies on determined Glossina spp. for transmission, the distribution range of WAT and T. brucei gambiense largely corresponds to that of the flies. To date, WAT is endemic in 24 countries of sub-Saharan Africa, and about 70 million people are considered at risk of infection with T. brucei gambiense [10]. Occasionally, WAT cases are imported to countries outside the endemic area [1] [2]. Most infections occur during the dry season, when larger populations of tsetse flies and humans gather around a limited number of water sources.

Sex distribution
Age distribution

Pathophysiology

The progression of hemolymphatic WAT to meningo-encephalitic WAT marks a turning point in the course of the disease. For trypanosomes to reach the cerebrospinal fluid, they have to cross the blood-brain barrier, but the mechanism underlying trypanosome invasion of the brain remain incompletely understood. The most widely accepted hypothesis to this end is that blood-brain barrier impairment is mediated by the immune system before the parasites can reach the central nervous system [11] [12].

Prevention

The World Health Organization aims at eliminating WTA as a public health problem by 2020, and distinct strategies have been followed to achieve this goal [13]. Vector control, case detection, and treatment are the pillars of disease prevention. An even more ambitious objective has been set for 2030: The transmission of the disease shall be terminated by this time [10] [13].

With regard to individual prophylaxis, travelers can only be recommended to avoid staying in rural areas of Central and West Africa. Those who are unable to do so should take measures to reduce their exposure to tsetse flies. They may wear long-sleeved, light-colored clothes and use insect repellant [6]. Medical prevention of WAT is not available.

Summary

African trypanosomiasis is considered a neglected tropical disease. There are two types of African trypanosomiasis, namely the West and East African variants. The former is caused by T. brucei gambiense, the latter by T. brucei rhodesiense. Both Trypanosoma species are highly vector-specific, so cases of West and East African trypanosomiasis have only been reported where the respective tsetse flies are endemic. These flies live in forests, wooded areas, and bushes, and those that are able to transmit WAT are distributed throughout sub-Saharan Africa. T. brucei gambiense has occasionally been isolated from pigs, sheep, cattle, and antelopes, but human beings are considered the main reservoir of the parasite, whose life cycle involves mammals and hematophagous Glossina spp [7]. The absence of greater reservoirs in wild animals allows focussing WAT prevention on the control of tsetse fly populations, the screening of populations at increased risk of infection, and treatment of infected people. By 2030, the World Health Organization hopes to have stopped disease transmission globally [10] [13]. Interestingly, WAT had almost been eradicated in the 1960s, but a collapse of surveillance and control activities in most endemic countries, often exacerbated by civil conflicts, led to its reemergence [7].

Patient Information

West African trypanosomiasis (WAT) is an infectious disease. It is caused by Trypanosoma brucei gambiense, a parasite transmitted by tsetse flies in Central and West Africa. The flies are mainly distributed in rural areas, so the risk of infection is low for casual travelers who don't leave the urban regions.

If a person is bitten by an infected fly, the affected site may turn into a red sore. Additional symptoms may not develop until months or even years later, when affected individuals suffer from intermittent fever and swollen cervical lymph nodes. General weakness and fatigue increasingly affect the patient's quality of life, which is why WAT is also referred to as Gambian sleeping sickness. During these early stages of WAT, trypanosomes distribute via blood and lymphatic vessels, but eventually, the central nervous system becomes involved. Then, patients may experience cognitive decline, confusion, memory impairment, motor deficits, and personality changes, among others. If left untreated, WAT leads to coma and death.

Fortunately, though, the disease is relatively easily diagnosed and treated with a high-cure rate. Trypanosomes and antibodies against these parasites can be detected in blood, lymph, and possibly cerebrospinal fluid. Even though the diagnosis of WAT may be confirmed after the identification of Trypanosoma brucei gambiense in peripheral blood, cerebrospinal fluid has to be examined to assess for central nervous system involvement. Depending on the stage of WAT, patients may be administered distinct drugs. Alertness, cognition, memory, and motor skills are very likely to improve under therapy, and the majority of patients recovers completely. In severe cases, neurological deficits may partially persist.

Prevention is the best cure. Those who travel to the Democratic Republic of Congo, the Central African Republic, or other sub-Saharan countries where tsetse flies are endemic, should avoid staying in rural areas. Measures should be taken to reduce the exposure to flies, e.g., by wearing long-sleeved, light-colored clothes and using insect repellant.

References

Article

  1. Lejon V, Boelaert M, Jannin J, Moore A, Buscher P. The challenge of Trypanosoma brucei gambiense sleeping sickness diagnosis outside Africa. Lancet Infect Dis. 2003; 3(12):804-808.
  2. Elliott I, Patel T, Shah J, Venkatesan P. West-African trypanosomiasis in a returned traveller from Ghana: an unusual cause of progressive neurological decline. BMJ Case Rep. 2014; 2014.
  3. Bisser S, Lumbala C, Nguertoum E, et al. Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study. PLoS Negl Trop Dis. 2016; 10(4):e0004608.
  4. Mitashi P, Hasker E, Lejon V, et al. Human african trypanosomiasis diagnosis in first-line health services of endemic countries, a systematic review. PLoS Negl Trop Dis. 2012; 6(11):e1919.
  5. Checchi F, Chappuis F, Karunakara U, Priotto G, Chandramohan D. Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis. PLoS Negl Trop Dis. 2011; 5(7):e1233.
  6. Bacchi CJ. Chemotherapy of human african trypanosomiasis. Interdiscip Perspect Infect Dis. 2009; 2009:195040.
  7. Brun R, Blum J, Chappuis F, Burri C. Human African trypanosomiasis. Lancet. 2010; 375(9709):148-159.
  8. Checchi F, Filipe JA, Barrett MP, Chandramohan D. The natural progression of Gambiense sleeping sickness: what is the evidence? PLoS Negl Trop Dis. 2008; 2(12):e303.
  9. Lindner AK, Priotto G. The unknown risk of vertical transmission in sleeping sickness--a literature review. PLoS Negl Trop Dis. 2010; 4(12):e783.
  10. Pandey A, Galvani A. Strategies for Trypanosoma brucei gambiense elimination. Lancet Glob Health. 2017; 5(1):e10-e11.
  11. Rodgers J. Human African trypanosomiasis, chemotherapy and CNS disease. J Neuroimmunol. 2009; 211(1-2):16-22.
  12. Sternberg JM. Human African trypanosomiasis: clinical presentation and immune response. Parasite Immunol. 2004; 26(11-12):469-476.
  13. Simarro PP, Cecchi G, Franco JR, et al. Monitoring the Progress towards the Elimination of Gambiense Human African Trypanosomiasis. PLoS Negl Trop Dis. 2015; 9(6):e0003785.

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Last updated: 2019-07-11 20:18