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African Trypanosomiasis

Sleeping Sickness

African trypanosomiasisis an illness endemic to sub-Saharan, also called African Sleeping Sickness.


Presentation

With T. b. rhodesiense, symptoms are seen within 1-3 weeks of the infective bite and the symptoms include high fever, chancre at the site of penetration, skin rash, headache, thrombocytopenia, myalgia and on rare occasions, splenomegaly, cardiac dysfunction and renal failure may be seen [9].

T.b gambiense does not have a specific presentation but weight loss, lymphadenopathy, pruritus, facial edema, myalgia, malaise, headache and fever may be recorded. The CNS gets involved after months to years of infection and this is characterized by severe headaches, somnolence, range of neurologic manifestations, mood disorders, behavior change, focal deficits, endocrine disorders etc. The clinical course of disease caused by T. b gambiense is less severe than T. b rhodesiense but if left untreated, they can be very fatal.

Fever
  • A 61-year-old Polish man was admitted to the Department because of high-grade fever and multi-organ dysfunction after a tourist trip to East Africa.[ncbi.nlm.nih.gov]
  • Intermittent fever. Myalgia. Headache. Pruritus, urticaria and facial oedema which sometimes occur.[patient.info]
  • The injected parasites mature further and divide in the blood and lymphatic system causing malaise, intermittent fever, rash and wasting.[symptoma.com]
  • He presented with an inoculation chancre and was treated with suramin within four days of fever onset. Two weeks earlier, HAT was also reported in a German traveller who had visited the Masai Mara area.[ncbi.nlm.nih.gov]
  • His travel history and rapid onset of symptoms, including fever, chills, headache, lethargy, and weight loss, were suggestive of Trypanosoma brucei rhodesiense infection, and trypanosomes were demonstrated in routine blood smears and buffy-coat preparations[ncbi.nlm.nih.gov]
Fatigue
  • Her recovery was notable for prolonged fatigue, which lasted for several months. Judy A. Streit, M.D. Eiyu Matsumoto, M.B. University of Iowa, Iowa City, IA[nejm.org]
  • Fever, severe headaches, irritability, extreme fatigue, swollen lymph nodes, and aching muscles and joints are common symptoms of sleeping sickness. Some people develop a skin rash.[web.archive.org]
  • Blood 2016 127:167; doi: A 49-year-old Spanish woman presented immediately on return to Spain from a 2-week visit to Tanzania with malaise, fatigue, arthralgia, and high fever (39 C). She had a medical history of dengue 4 years ago.[bloodjournal.org]
  • These include fever, rash, swelling of the face and hands, headaches, fatigue, aching muscles and joints, itching skin, and swollen lymph nodes. Weight loss occurs as the illness progresses.[web.archive.org]
Weight Loss
  • His travel history and rapid onset of symptoms, including fever, chills, headache, lethargy, and weight loss, were suggestive of Trypanosoma brucei rhodesiense infection, and trypanosomes were demonstrated in routine blood smears and buffy-coat preparations[ncbi.nlm.nih.gov]
  • The illness progresses after a few weeks to weight loss, as well as personality changes, slurred speech, seizures, difficulty balancing and walking resulting from central nervous system failure.[iamat.org]
  • Anorexia, wasting and weight loss. Irritability, tremors, and increased muscle tone are usual signs; sometimes ataxia or hemiparesis occurs, but rarely meningism.[patient.info]
  • Weight loss occurs as the illness progresses. Progressive confusion, personality changes, daytime sleepiness with nighttime sleep disturbances, and other neurologic problems occur after the infection has invaded the central nervous system.[web.archive.org]
Anemia
  • Back to full disease list Other Names: Nagana, Tsetse Disease, Tsetse Fly Disease, Trypanosomosis African animal trypanosomiasis (AAT) is a parasitic disease that causes anemia, loss of condition, and emaciation in livestock.[cfsph.iastate.edu]
  • This may be the result of immune-mediated reactions against antigens on red blood cells, cardiac tissue, and brain tissue, resulting in hemolysis, anemia, pancarditis, and meningoencephalitis.[symptoma.com]
  • […] reference imported from Wikimedia project English Wikipedia symptoms Winterbottom's sign 1 reference stated in WikiSkripta periodic fever 1 reference stated in WikiSkripta headache 1 reference stated in WikiSkripta malaise 1 reference stated in WikiSkripta anemia[wikidata.org]
  • These macrophages release harmful chemicals such as TNF's, cause organ lesions, anemia, and cachexia.[austincc.edu]
  • If left untreated, the parasitic infection causes anemia, heart, kidney, and endocrine failure, and neurologic damage. Subsequently patients develop confusion, disruption of the sleep cycle, and mental deterioration.[icd10data.com]
Malaise
  • The injected parasites mature further and divide in the blood and lymphatic system causing malaise, intermittent fever, rash and wasting.[symptoma.com]
  • Symptoms tend to be nonspecific, including: General malaise. Intermittent fever. Myalgia. Headache. Pruritus, urticaria and facial oedema which sometimes occur.[patient.info]
  • Blood 2016 127:167; doi: A 49-year-old Spanish woman presented immediately on return to Spain from a 2-week visit to Tanzania with malaise, fatigue, arthralgia, and high fever (39 C). She had a medical history of dengue 4 years ago.[bloodjournal.org]
  • […] health specialty Infectious Disease 1 reference imported from Wikimedia project English Wikipedia symptoms Winterbottom's sign 1 reference stated in WikiSkripta periodic fever 1 reference stated in WikiSkripta headache 1 reference stated in WikiSkripta malaise[wikidata.org]
Splenomegaly
  • Lymphadenopathy and splenomegaly led us eventually to the diagnosis of sleeping sickness. After treatment with suramin his spermiogram returned to normal.[ncbi.nlm.nih.gov]
  • We demonstrate that HAT patients exhibit parasitaemia-independent plasma endotoxaemia, and that this is associated with splenomegaly and lymphadenopathy. Endotoxin concentrations normalize rapidly after treatment.[ncbi.nlm.nih.gov]
  • Infested lymph nodes and increased lymphocyte levels in the spleen lead to fibrosis but it rarely every gets to splenomegaly.[symptoma.com]
  • The disease progresses through two phases: Stage 1 is marked by fever, lymphadenopathy, splenomegaly, and myocarditis.[medical-dictionary.thefreedictionary.com]
  • Skin invasion for enhanced transmission is likely a powerful evolutionary force driving extravasation, suggesting that the generalised tissue penetration underlying pathogenesis (i.e. splenomegaly, hepatomegaly, CNS invasion) is a secondary epiphenomenon[elifesciences.org]
Generalized Lymphadenopathy
  • Symptoms include characteristic skin lesions, intermittent fever, headache, rigors, transient edema, generalized lymphadenopathy, and often fatal meningoencephalitis.[merckmanuals.com]
Severe Clinical Course
  • A severe clinical course of acute rhodesiense trypanosomiasis with renal failure, respiratory distress, disseminated intravascular coagulation syndrome, haemolysis, liver insufficiency and myocarditis was confirmed.[ncbi.nlm.nih.gov]
Loss of Appetite
  • Early findings include insomnia, loss of appetite, behavioural changes, mood disorders, apathy, and headaches. A variety of muscle disorders may follow, including tremors and disturbances of speech, gait, and reflexes.[dermnetnz.org]
  • People who experience symptoms may have fevers, rashes, extreme tiredness, vomiting, loss of appetite, or swollen lymph nodes. The side of the face where the infected feces were rubbed into an eye or a bug bite may swell.[humanillnesses.com]
Hepatosplenomegaly
  • Abdominal and pelvic MRI showed hepatosplenomegaly and multiple enlarged lymph nodes. FDG PET/CT showed generalized hypermetabolic lymph nodes, diffuse FDG uptake of the spleen, and hepatosplenomegaly mimicking lymphoma.[ncbi.nlm.nih.gov]
  • On admission, his clinical status was severe, with high fever of 41ºC, preceded by chills, bleeding from the gums and oral mucosa, haemorrhages at the sites of venipuncture, numerous ecchymoses, fine-spotted skin rash, tachycardia, hepatosplenomegaly,[ncbi.nlm.nih.gov]
  • Hepatosplenomegaly and lymphadenopathy were absent.[bloodjournal.org]
  • In the first stage, when trypanosomes multiply in the haemolymphatic system, infected individuals experience intermittent episodes of fever and develop lymphadenopathy, and other non‐specific signs such as hepatosplenomegaly and skin rashes ( Stich 2002[doi.org]
Hepatomegaly
  • Skin invasion for enhanced transmission is likely a powerful evolutionary force driving extravasation, suggesting that the generalised tissue penetration underlying pathogenesis (i.e. splenomegaly, hepatomegaly, CNS invasion) is a secondary epiphenomenon[elifesciences.org]
Chancre
  • Skin findings included a fluctuant, indurated, tsetse-fly bite site (chancre) and a fleeting, erythematous, macular eruption. The diagnosis was confirmed by the presence of the organism in peripheral blood smears.[ncbi.nlm.nih.gov]
  • He presented with an inoculation chancre and was treated with suramin within four days of fever onset. Two weeks earlier, HAT was also reported in a German traveller who had visited the Masai Mara area.[ncbi.nlm.nih.gov]
  • Occasionally this causes a skin chancre at the site of penetration. The injected parasites mature further and divide in the blood and lymphatic system causing malaise, intermittent fever, rash and wasting.[symptoma.com]
Insect Bite
  • He gave no history of a painful insect bite but presented with classical early signs of sleeping sickness (a primary chancre, regional lymphadenopathy, circinate erythema and a cyclical fever pattern).[ncbi.nlm.nih.gov]
  • He gave no history of a painful insect bite but presented with classic early signs of sleeping sickness (a primary chancre, regional lymphadenopathy, circinate erythema, and a cyclical fever pattern).[ncbi.nlm.nih.gov]
  • How can I prevent African trypanosomiasis and prevent other insect bites? Wear protective clothing, including long-sleeved shirts and pants. The tsetse fly can bite through thin fabrics, so clothing should be made of medium-weight material.[web.archive.org]
  • How can I prevent African trypanosomiasis and other insect bites? Wear protective clothing, including long-sleeved shirts and pants. The tsetse fly can bite through thin fabrics, so clothing should be made of medium-weight material.[web.archive.org]
Pruritus
  • T.b gambiense does not have a specific presentation but weight loss, lymphadenopathy, pruritus, facial edema, myalgia, malaise, headache and fever may be recorded.[symptoma.com]
  • Pruritus, urticaria and facial oedema which sometimes occur.[patient.info]
  • Side effects include nausea, vomiting, pruritus (itching), uricaria (hives), hypesthesia (decreased sensitivity), photophobia (increased sensitivity to light), and peripheral neuropathy.[web.stanford.edu]
  • The multivariable exploration of pretreatment risk factors for reactions at the injection site (261/1055 patients) identified as predictors: age less than 15 years (odds ratio 1.62, 95% confidence interval 1.16 to 2.26; P 0.005) and pruritus (odds ratio[doi.org]
Eruptions
  • Skin findings included a fluctuant, indurated, tsetse-fly bite site (chancre) and a fleeting, erythematous, macular eruption. The diagnosis was confirmed by the presence of the organism in peripheral blood smears.[ncbi.nlm.nih.gov]
  • Frequently there are transient skin eruptions characterized by erythema or edema. These symptoms and signs may progress to the phase of central nervous system.[histopathology-india.net]
  • In 1901, a devastating epidemic erupted in Uganda, killing more than 250,000 people, including about two-thirds of the population in the affected lakeshore areas.[en.wikipedia.org]
Myalgia
  • A previously healthy 60-year-old woman presented with a 2-to-3-day history of fevers, chills, myalgias, headache, and two pruritic areas on her back.[nejm.org]
  • T.b gambiense does not have a specific presentation but weight loss, lymphadenopathy, pruritus, facial edema, myalgia, malaise, headache and fever may be recorded.[symptoma.com]
  • Myalgia. Headache. Pruritus, urticaria and facial oedema which sometimes occur.[patient.info]
  • Adults presenting with arthralgia or myalgia had a lower risk of major toxicity. An explanation might be that these symptoms are indicative of an earlier stage of the disease progression.[doi.org]
Arthralgia
  • Blood 2016 127:167; doi: A 49-year-old Spanish woman presented immediately on return to Spain from a 2-week visit to Tanzania with malaise, fatigue, arthralgia, and high fever (39 C). She had a medical history of dengue 4 years ago.[bloodjournal.org]
  • English Wikipedia symptoms Winterbottom's sign 1 reference stated in WikiSkripta periodic fever 1 reference stated in WikiSkripta headache 1 reference stated in WikiSkripta malaise 1 reference stated in WikiSkripta anemia 1 reference stated in WikiSkripta Arthralgia[wikidata.org]
  • Adults presenting with arthralgia or myalgia had a lower risk of major toxicity. An explanation might be that these symptoms are indicative of an earlier stage of the disease progression.[doi.org]
Headache
  • Despite the presence of headaches, nuchal rigidity, and CSF pleocytosis, he was treated for non-CNS African trypanosomiasis, based on a normal CSF IgM level.[ncbi.nlm.nih.gov]
  • The most common side effects observed were vomiting, nausea, headache, insomnia, weakness, dizziness and tremor.[ema.europa.eu]
  • T.b gambiense does not have a specific presentation but weight loss, lymphadenopathy, pruritus, facial edema, myalgia, malaise, headache and fever may be recorded.[symptoma.com]
  • Kampala — IT starts with a headache, joint pains and fever. It is the kind you would expect to get over quickly. But after a while, things get worse. You fall asleep most of the time, are confused and get intense pains and convulsions.[allafrica.com]
  • The parasite initially lives in the bloodstream of the human host causing fever and headaches, but eventually crosses into the brain where it causes irreversible neurological damage. Without treatment, the disease is fatal.[web.archive.org]
Seizure
  • Severe reactions affected 138 (13.1%) patients (mainly seizures, fever, diarrhoea, and bacterial infections), leading to 15 deaths.[ncbi.nlm.nih.gov]
  • 1/149 6/170 Skin reactions Graded melarsoprol 26 days vs fixed melarsoprol 10 days Pepin 2006 3/70 6/170 Confusion 7/70 4/170 Seizures 0/70 6/170 Skin reactions Eflornithine monotherapy Eflornithine 7 days vs 14 days Pepin 2000 7/158 10/163 Seizures[doi.org]
  • Seizures appeared consistently at the beginning of treatment (median day 3). Patients recovered well from seizures and only two intractable cases necessitated stopping treatment.[doi.org]
  • Behavioural changes such as mania or psychosis with speech disorders and seizures. Seizures occur in children but rarely in adults. Stupor and coma (hence the name sleeping sickness).[patient.info]
  • Congenital African trypanosomiasis occurs in children, causing psychomotor retardation and seizure disorders. African trypanosomiasis has no sexual or racial predilection.[emedicine.medscape.com]
Insomnia
  • The second phase of the illness usually becomes evident 1 to 2 years after infection and is characterized by fever, headache, muscle and joint pain, itchy skin, weakness, weight loss, insomnia, confusion, personality changes, slurred speech, seizures,[iamat.org]
  • General symptoms include: Mood changes, anxiety Fever, sweating Headache Weakness Insomnia at night Sleepiness during the day (may be uncontrollable) Swollen lymph nodes all over the body Swollen, red, painful nodule at site of the fly bite Diagnosis[nlm.nih.gov]
  • The primary symptom of the disease is hypersomnia or excessive sleep, although the disease can also cause insomnia.[house.wikia.com]
  • The most common side effects observed were vomiting, nausea, headache, insomnia, weakness, dizziness and tremor.[ema.europa.eu]
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]
  • Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible[ncbi.nlm.nih.gov]
  • The CNS gets involved after months to years of infection and this is characterized by severe headaches, somnolence, range of neurologic manifestations, mood disorders, behavior change, focal deficits, endocrine disorders etc.[symptoma.com]
  • Our study suggests that in states such as trypanosomal sleeping sickness or disulfiram treatment, remotely formed tryptophol gains ready access to brain (it is 100% cleared in a single capillary passage), and could thus cause somnolence.[ncbi.nlm.nih.gov]
Personality Change
  • A 33 year old male African patient, a former resident of Cameroon, presented with a 4-month history of progressive personality changes.[ncbi.nlm.nih.gov]
  • The illness progresses after a few weeks to weight loss, as well as personality changes, slurred speech, seizures, difficulty balancing and walking resulting from central nervous system failure.[iamat.org]
  • 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]
  • Progressive confusion, personality changes, and other neurologic problems occur after infection has invaded the central nervous system. If left untreated, infection becomes worse and death will occur within months.[web.archive.org]

Workup

Although general laboratory studies may be helpful in the diagnosis of African trypanosomiasis (sleeping sickness), a definitive diagnosis of T brucei infection requires actual detection of trypanosomes in blood, lymph nodes, cerebrospinal fluid (CSF), skin chancre aspirates, or bone marrow. In areas where diagnostic studies are not readily available, however, symptomatic improvement after empiric treatment is the usual confirmatory test. Buffy-coat preparations concentrate the parasite [9].

Treatment

Prehospital care of African trypanosomiasis (sleeping sickness) centers on management of the acute symptoms of fever and malaise in conjunction with close monitoring of the patient’s neurologic status. In the emergency department, if central nervous system (CNS) symptoms are severe, airway management to prevent aspiration becomes important, along with an immediate blood smear, complete blood count (CBC), and lumbar puncture for trypanosome detection [10].

Prognosis

Patients of stage 1 trypanosomiasis recover fully after treatment. In stage 2 trypanosomiasis however, the manifestations in the CNS ultimately become fatal if left untreated. With drugs that work inside the CNS like melasorprol, the cure rate is more than 95% [8].

Etiology

In humans, there are two subspecies that are responsible for the initiation of the disease. In west and central Africa, the disease is caused by Trypanosoma brucei gambiense [5]. Trypanosoma brucei rhodesiense has a limited geographical range and it is responsible for causing the disease in east and southern Africa. Additionally, Trypanosoma brucei brucei is responsible affecting animals bit it doesn’t affect humans.

Epidemiology

In the United States, all cases of African trypanosomiasis is imported from Africa by travellers who go to areas that have been designated as endemic. Infections amongst travellers however, is around 1 case per year, with some years not getting any records. Most of the infections are of T brucei rhodesiense and these are acquired in game parks in Eastern Africa.

Internationally, this disease is confined to tropical Africa covering the north of South Africa to south of Algeria, Libya and Egypt. Outside this area, the prevalence of African Trypanosomiasis varies by country and region [4]. Major outbreaks occurred in Angola, DR Congo and Sudan in 2005. African trypanosomiasis remains a challenge in the Central African Republic, Chad, Congo, Cote d’Ivoire, Tanzania, Uganda, Malawi and Guinea.

In Zimbabwe, Zambia, Rwanda, Nigeria, Mozambique, Kenya, Gabon, Equatorial Guinea, Cameroon and Burkina Faso, less than 50 cases are reported each year. The transmission of T.Brucei seems to have stopped in Togo, Swaziland, Sierra Leone, Senegal, Niger, Namibia, Mali, Liberia, Guinea Bissau, Ghana, Gambia, Ethiopia, Burundi, Bostwana and Benin as no new case has been reported for decades now.

The African Trypanosomiasis condition is a threat to millions of people in 36 countries in sub Saharan Africa. The situation is difficult to assess presently because of the lack of diagnostic expertise and surveillance in these locations.

Sex distribution
Age distribution

Pathophysiology

The parasites, trypanosomes are parasites known for a 2-host life cycle namely mammalian and arthropod. The life cycle begins when the trypanosome is ingested during the course of a blood meal from either an animal reservoir (East African trypanosomiasis) or a human reservoir (West African trypanosomiasis). The parasites multiply over a 2-3 week period in the mid gut of the fly from where they move to its salivary gland, developing into an epimastigote [6].

Humans get infected with T brucei following the bite of a fly. Occasionally this causes a skin chancre at the site of penetration. The injected parasites mature further and divide in the blood and lymphatic system causing malaise, intermittent fever, rash and wasting. Over time, the parasites spread into the Central Nervous System where behavioral and neurologic changes like encephalitis and coma. In extreme cases, death may occur.

The parasites escape the initial host defense mechanisms through extensive antigenic variation of parasite surface glycoproteins (major variant surface glycoprotein [VSG]). This evasion of humoral immune responses contributes to virulence. During the parasitemia, most pathologic changes occur in the hematologic, lymphatic, cardiac, and central nervous systems. This may be the result of immune-mediated reactions against antigens on red blood cells, cardiac tissue, and brain tissue, resulting in hemolysis, anemia, pancarditis, and meningoencephalitis [7].

Skin problems like persistent urticaria, puritus and facial edema are caused by hypersensitivity reaction. Infested lymph nodes and increased lymphocyte levels in the spleen lead to fibrosis but it rarely every gets to splenomegaly. When the monocytes, macrophages and plasma cells get into the blood vessels increased vascular permeability and endarteritis occur.

Prevention

No vaccine is available for African trypanosomiasis. Chemoprophylaxis is unavailable.

Avoidance of travel to areas heavily infested with tsetse flies is recommended. Tsetse flies are attracted to moving vehicles and dark contrasting colors. They are not affected by insect repellants and can bite through lightweight clothing. At-risk travelers are advised to wear wrist- and ankle- length clothing that is made of medium-weight fabric in neutral colors.

Summary

More commonly known as sleeping sickness, African Trypanosomiasis is an ailment that is endemic in sub-Saharan Africa [1]. It is caused by Trypanosoma brucei, a flagellate protozoan that exists in two morphologically identical subspecies namely: T brucei gambiense (West African or Gambian African trypanosomiasis) and T brucei rhodesiense (East African or Rhodesian African trypanosomiasis).

Both parasites are passed on to human hosts via the bite of already infected tsetse flies. Glossina palpalis transmits T brucei gambiense and Glossina Morsitans transmits T brucei rhodesiense. Both are only found in Africa.

For West African trypanosomiasis, humans are the exclusive reservoir of infection. With East African trypanosomiasis on the other hand, there is a zoonotic infection with animal vectors. African trypanosomiasis must not be confused with American trypanosomiasis. The latter is caused by Trypanosoma Cruzi and has different vectors, clinical manifestations as well as therapies.
The main factor that is epidemiologic in African trypanosomiasis is the contact between humans and tsetse flies [2].

The interaction is further influenced by increase in tse tse fly density, feeding habits that have continued to change, continued expansion into tsetse fly infested by humans, and increasing number of immunologically naïve individuals in areas that were formally endemic. The major outbreak between 1920 and 1950 brought about extensive treatment and immunity for 50 years. Infection is now recurring though meaning that the same populatison are losing their immunity [3].

Patient Information

Following recovery from stage-2 disease, a lumbar puncture is required every 3 months for the first year in patients with East African disease and every 6 months for 2 years in patients with West African disease.

Relapse has occurred if symptoms return, CSF pleocytosis appears, or if trypanosomes are still present in blood or CSF. A persistently elevated CSF white cell count can be found in recovering patients, so a change in white cell count is more helpful as an indicator of relapse.

If relapse occurs, treatment with melarsoprol or eflornithine should be repeated.

References

Article

  1. Truc P, Lando A, Penchenier L, Vatunga G, Josenando T. Human African trypanosomiasis in Angola: clinical observations, treatment, and use of PCR for stage determination of early stage of the disease. Trans R Soc Trop Med Hyg. Jan 2012;106(1):10-4.
  2. Simarro PP, Cecchi G, Franco JR, Paone M, Fèvre EM, Diarra A, et al. Risk for human african trypanosomiasis, central Africa, 2000-2009. Emerg Infect Dis. Dec 2011;17(12):2322-4.
  3. Kohagne TL, M'eyi MP, Kamkuimo RG, Kaba D, Louis JF, Mimpfoundi R. Transmission of human African trypanosomiasis in the Komo-Mondah focus, Gabon. Pan Afr Med J. 2011;8:36.
  4. Abramowicz M. Drugs For Parasitic Infections. In: Abramowicz M, ed. The Medical Letter on Drugs and Therapeutics. New Rochelle, NY: The Medical Letter, Inc; 2000:1-12.
  5. Bisser S, N'Siesi FX, Lejon V, Preux PM, Van Nieuwenhove S, Miaka Mia Bilenge C, et al. Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness. J Infect Dis. Feb 1 2007;195(3):322-9.
  6. Kennedy PG. Human African trypanosomiasis of the CNS: current issues and challenges. J Clin Invest 2004; 113:496.
  7. Barrett MP, Burchmore RJ, Stich A, et al. The trypanosomiases. Lancet 2003; 362:1469.
  8. Jamonneau V, Ilboudo H, Kaboré J, et al. Untreated human infections by Trypanosoma brucei gambiense are not 100% fatal. PLoS Negl Trop Dis 2012; 6:e1691.
  9. Urech K, Neumayr A, Blum J. Sleeping sickness in travelers - do they really sleep? PLoS Negl Trop Dis 2011; 5:e1358.
  10. Pépin J, Méda HA. The epidemiology and control of human African trypanosomiasis. Adv Parasitol 2001; 49:71.

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Last updated: 2019-07-11 20:45