African Trypanosomiasis (Sleeping Sickness)

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Practice Essentials

African trypanosomiasis (sleeping sickness) (see the image below) is an illness endemic to sub-Saharan Africa. It is caused by two subspecies of the flagellate protozoan Trypanosoma brucei, which are transmitted to human hosts by bites of infected tsetse flies.



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African trypanosomiasis (sleeping sickness). Human trypanosomes blood smear.

Signs and symptoms

Symptoms of stage 1 (early or hemolymphatic stage) disease may include the following:

Symptoms of stage 2 (late or neurologic stage) disease may include the following:

Physical findings in stage 1 (early or hemolymphatic stage) disease may include the following:

Physical findings in stage 2 (late or neurologic stage) disease may include the following:

See Presentation for more detail.

Diagnosis

Although general laboratory studies may be helpful, a definitive diagnosis of African trypanosomiasis requires actual detection of trypanosomes.

Significant laboratory abnormalities include the following:

Studies performed to detect trypanosomes include the following:

CSF assay is also done to measure white blood cell (WBC) counts, protein, and IgM in patients with parasitemia or positive serologies or symptoms.

The following studies may also be considered:

See Workup for more detail.

Management

The type of drug treatment used depends on the type and stage of disease, as follows:

Fexinidazole is a promising new oral drug recently recommended by the European Medicines Agency for the treatment of both stages of West African trypanosomiasis.

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

In both early- and late-stage trypanosomiasis, symptoms usually resolve after treatment, and the parasitemia clears on repeat blood smears.

Patients who have recovered from late-stage East African trypanosomiasis should undergo lumbar punctures every 3 months for the first year. Patients who have recovered from West African trypanosomiasis should undergo lumbar punctures every 6 months for 2 years.

See Treatment and Medication for more detail.

Background

African trypanosomiasis, also referred to as sleeping sickness, is an illness endemic to sub-Saharan Africa. It is caused by the flagellate protozoan Trypanosoma brucei, which exists in two morphologically identical subspecies transmitted to human hosts by bites of infected tsetse flies, which are found only in Africa, as follows:

Tsetse flies inhabit rural areas, living in the woodlands and thickets that dot the East African savannah. In central and West Africa, they live in the forests and vegetation along streams. Tsetse flies bite during daylight hours. Both male and female flies can transmit the infection, but, even in areas where African trypanosomiasis is endemic, only a very small percentage of flies are infected. Although the vast majority of infections are transmitted by the tsetse fly, other modes of transmission are possible. Occasionally, a pregnant woman can pass the infection to her unborn baby. In theory, the infection can also be transmitted via blood transfusion or sexual contact, but such cases have rarely been documented.

In West African trypanosomiasis, the reservoirs of infection for these vectors are exclusively human. East African trypanosomiasis, however, is a zoonotic infection with animal vectors. African trypanosomiasis must be distinguished from American trypanosomiasis, which is caused by Trypanosoma cruzi and has different vectors, clinical manifestations, and therapies.

The major epidemiological factor in African trypanosomiasis is contact between humans and tsetse flies. This interaction is influenced by an increasing tsetse fly density, changing feeding habits, and expanding human development into tsetse fly–infested areas.

Pathophysiology and Etiology

Trypanosomes are parasites with a two-host life cycle: mammalian and arthropod. The life cycle starts when the trypanosomes are ingested during a blood meal by the tsetse fly from either a human reservoir (West African trypanosomiasis) or an animal reservoir (East African trypanosomiasis). The trypanosomes multiply over a period of 2-3 weeks in the fly midgut; then, the trypanosomes migrate to the salivary gland.



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Trypanosoma life cycle. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.....

Humans are infected with T brucei after a fly bite, which occasionally causes a painful skin chancre at the site 5-15 days later. The injected parasites further mature and divide in the blood and lymphatic system, causing malaise, intermittent fever, rash, and wasting. Eventually, the parasitic invasion reaches the central nervous system (CNS), causing behavioral and neurologic changes (eg, encephalitis and coma). Death may occur.

Innate immunity to trypanosomes results from apolipoprotein L-1 (APOL1), which bind to high-density lipoprotein (HDL) in serum. This protein causes lysis of the trypanosomes when taken up through endocytosis. Disease develops when resistance to APOL1 is acquired.

The parasites escape the 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 and leads to waves of parasitemia. 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.

A hypersensitivity reaction causes skin problems, including persistent urticaria, pruritus, and facial edema. Increased lymphocyte levels in the spleen and lymph nodes infested with the parasite lead to fibrosis but rarely to splenomegaly. Monocytes, macrophages, and plasma cells infiltrate blood vessels, causing endarteritis and increased vascular permeability.

The gastrointestinal (GI) system is also affected. Kupffer cell hyperplasia occurs in the liver, along with portal infiltration and fatty degeneration. Hepatomegaly is rare. A pancarditis may develop secondary to extensive cellular infiltration and fibrosis (particularly in the East African form). Arrhythmia or cardiac failure can cause death before the development of CNS manifestations (including perivascular infiltration into the interstitium in the brain and spinal cord, leading to meningoencephalitis with edema, bleeding, and granulomatous lesions.

In rare instances, parasitic transmission can result from blood transfusions. Accidental transmission in the laboratory has also been implicated in a small number of cases.

Epidemiology

United States statistics

All cases of African trypanosomiasis in the United States are imported from Africa by travelers to endemic areas. Infections among travelers are rare (< 1 case/year among US travelers). Most of these infections are caused by T brucei rhodesiense and are acquired in East African game parks.

International statistics

African trypanosomiasis is confined to tropical Africa between latitudes 15°N and 20°S, or from north of South Africa to south of Algeria, Libya, and Egypt.[1] The prevalence of African trypanosomiasis outside this area varies by country and region. In 2005, major outbreaks occurred in Angola, the Democratic Republic of Congo, and Sudan.[2] In the Central African Republic, Chad, Congo, Côte d’Ivoire, Guinea, Malawi, Uganda, and Tanzania, African trypanosomiasis remains a major public health problem.[3, 4, 5]

Fewer than 50 new cases per year are reported in Burkina Faso, Cameroon, Equatorial Guinea, Gabon, Kenya, Mozambique, Nigeria, Rwanda, Zambia, and Zimbabwe.[6] In Benin, Botswana, Burundi, Ethiopia, Gambia, Ghana, Guinea Bissau, Liberia, Mali, Namibia, Niger, Senegal, Sierra Leone, Swaziland, and Togo, T brucei transmission seems to have stopped, and no new cases of African trypanosomiasis have been reported for several decades.

African trypanosomiasis threatens millions of people in 36 countries of sub-Saharan Africa. The current situation is difficult to assess in numerous endemic countries, because of a lack of surveillance and diagnostic expertise.

In 1986, a panel of experts convened by the World Health Organization (WHO) estimated that 70 million people lived in areas where transmission of African trypanosomiasis is possible. In 1998, almost 40,000 cases of the disease were reported, but in view of the remoteness of the affected regions and the focal nature of the disease, it was clear that this number did not reflect the true situation. It was estimated that 300,000-500,000 more cases were undiagnosed and thus went untreated.

During some epidemic periods, prevalence reached 50% in several villages in the Democratic Republic of Congo, Angola, and South Sudan. African trypanosomiasis was considered the first or second greatest cause of mortality in those communities, even ahead of HIV infection and AIDS. By 2005, surveillance had been reinforced, and the number of new cases reported throughout the continent had been substantially reduced; between 1998 and 2004, the figures for both forms of African trypanosomiasis together fell from 37,991 to 17,616.

In 2009, the World Health Organization (WHO) indicated that the number of new African trypanosomiasis cases reported dropped below 10,000 (9,878) for the first time in 50 years, and the estimated number of actual cases was 30,000. This plummeting trend continued, and, in 2014, only 3,796 cases were reported, with less than 15,000 estimated actual cases.

Age-, sex-, and race-related demographics

Exposure can occur at any age. Congenital African trypanosomiasis occurs in children, causing psychomotor retardation and seizure disorders. African trypanosomiasis has no sexual or racial predilection.

Prognosis

In early (stage 1) trypanosomiasis, most patients recover fully after treatment. In late (stage 2) trypanosomiasis, the CNS manifestations are ultimately fatal if untreated. The cure rate approaches 95% with drugs that work inside the CNS (eg, melarsoprol).

The symptoms of East African trypanosomiasis develop more quickly (starting 1 month after a bite) than the symptoms of West African trypanosomiasis, which can begin months to a year after the first bite.

Both types of African trypanosomiasis cause the same generalized symptoms, including intermittent fevers, rash, and lymphadenopathy. Notably, individuals with the East African form are more likely to experience cardiac complications and develop CNS disease more quickly, within weeks to a month. The CNS manifestations of behavioral changes, daytime somnolence, nighttime insomnia, stupor, and coma result in death if untreated.

In West African trypanosomiasis, the asymptomatic phase may precede onset of fevers, rash, and cervical lymphadenopathy. If unrecognized, the symptoms then progress to weight loss, asthenia, pruritus, and CNS disease with a more insidious onset. Meningismus is rare. Death at this point is usually due to aspiration or seizures caused by CNS damage.

History

Symptoms of stage 1 (early or hemolymphatic stage) African trypanosomiasis (sleeping sickness) include the following:

Symptoms of stage 2 (late or neurologic stage) African trypanosomiasis include the following:

Physical Examination

Physical findings in stage 1 (early or hemolymphatic stage) African trypanosomiasis include the following:

Physical findings in stage 2 (late or neurologic stage) African trypanosomiasis include the following:

Complications

Complications of African trypanosomiasis may include the following:

Approach Considerations

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.[7]

General Blood Studies and Serology

The most significant laboratory abnormalities in African trypanosomiasis include anemia, hypergammaglobulinemia, low complement levels, elevated erythrocyte sedimentation rate (ESR), thrombocytopenia, and hypoalbuminemia (but not eosinophilia or abnormal liver function). In the West African form, the total immunoglobulin M (IgM) level is notably higher in blood and CSF (along with a high CSF protein level).

Serologic antibody detection

Field serology-based diagnosis of African trypanosomiasis has been slow to progress. Although many research tools are available for diagnosis, few are used clinically in endemic areas.[8]

The standard serologic assay for diagnosing West African trypanosomiasis is the card agglutination test for trypanosomiasis (CATT). The CATT can be conducted in the field without electricity, and results are available in only 10 minutes. It is highly sensitive (96%) but less specific because of cross-reactivity with animal trypanosomes. Commercial antibody tests for Eastern African trypanosomiasis are not available.

Antigen detection tests based on enzyme-linked immunosorbent assay (ELISA) technology have been developed. They have shown inconsistent results and are not yet commercially available.

An individual serological rapid diagnostic test for the diagnosis of West African trypanosomiasis was recently developed and commercialized (HAT Sero-K-SeT). Its diagnostic performance was shown to be similar to that of CATT.[9]

Culture of CSF, blood, bone marrow aspirate, or tissue specimens can be performed in liquid media. Other tests that have been developed but are not frequently used in clinical settings include antibody detection in the CSF and intrathecal space (low sensitivity), polymerase chain reaction (PCR), and serum proteomic tests. Research tools such as isoenzyme analysis and restriction fragment length polymorphism (RFLP) are used for definitive subspecies identification.

Blood Smear

A wet smear of unstained blood or a Giemsa-stained thick smear (more sensitive; Wright and Leishman stains are inadequate) is examined to look for mobile trypanosomes (see the image below); the organisms remain mobile for only 15-20 minutes. This technique is most sensitive in the early stages of the disease, when the number of circulating parasites is highest (≥5000/mL), particularly in T brucei rhodesiense (East African) trypanosomiasis.



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Trypanosoma brucei in a thin blood smear stained with Giemsa. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.....

Better assays are now available, including the hematocrit centrifugation technique for buffy coat examination and the miniature anion-exchange centrifugation technique (mAECT), which filters out the red blood cells (RBCs) but not the trypanosomes. This test can be used to detect serum parasite levels as low as 5 /mL; the test can be repeated on subsequent days to increase the yield when results are negative.

Chancre aspirate can be used as a wet preparation, especially in East African trypanosomiasis, but a blood smear is more sensitive.

Aspiration of Lymph Node or Bone Marrow

Lymph node aspiration at a high dry magnification (´400) is commonly used as a rapid test for trypanosomes. It requires an immediate search for parasites because, as noted (see above), the organisms are mobile for only 15-20 minutes. This test has more utility in T brucei gambiense (West African) trypanosomiasis.

Bone marrow aspiration may yield positive results in some patients.

Lumbar Puncture and CSF Assay

Lumbar puncture should be performed whenever trypanosomiasis is suspected. CSF is examined for the purposes of detecting trypanosomes and measuring white blood cell (WBC) counts, protein, and IgM in patients with parasitemia or positive serologies or symptoms. CSF examination helps to diagnose and stage the disease. However, a negative result does not necessarily rule out the diagnosis.

The double centrifugation technique is the most sensitive method for detecting the trypanosomes. Other findings that may be noted on evaluation of the CSF include elevated WBC counts, elevated IgM levels, elevated total protein levels, and raised intracranial pressure. An uncommon characteristic finding is Mott cells, which are thought to be large eosinophilic plasma cells containing IgM that have failed to secrete their antibodies.

Increased intrathecal synthesis of IgM has been found to be the most sensitive indicator of CNS involvement in African trypanosomiasis. CNS disease can manifest early in East African trypanosomiasis.

Other Studies

Computed tomography (CT) and magnetic resonance imaging (MRI) of the head reveal cerebral edema and white matter enhancement, respectively, in patients with late-stage African trypanosomiasis.

In cases of neurologic involvement, electroencephalography (EEG) usually shows slow wave oscillations (delta waves), a nonspecific finding.

Approach Considerations

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.

If late stage disease is present or CNS disease complications and coma occur, intensive care unit (ICU) staff are needed while treatment is administered (ie, melarsoprol for East African trypanosomiasis or eflornithine for West African trypanosomiasis). Potential adverse effects from such drugs, including hematologic, renal, and hepatic function must be monitored.

Pharmacologic Therapy

The type of drug treatment used depends on the type and stage of African trypanosomiasis (sleeping sickness). Management recommendations were published in The Medical Letter on Drugs and Therapeutics in March 2000 (see the Table below).[10]

Table. Medications Recommended for Treatment of African Trypanosomiasis



View Table

See Table

Since 2009, the WHO has adopted the combination of eflornithine and nifurtimox (NECT) as first-line treatment for second-stage gambiense human African trypanosomiasis in all countries with endemic disease. The combination of both drugs reduces the duration of eflornithine monotherapy treatment and is easier to administer, while improving the level of efficacy and safety.

In November 2018, the European Medicines Agency (CHMP) adopted a positive opinion for fexinidazole as the first oral-only regimen for the treatment of first–stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis due to T brucei gambiense in adults and children aged 6 years and older and who weigh 20 kg or more.[11]

In a randomized trial including 394 patients with late-stage human African trypanosomiasis due to T brucei gambiense treated with fexinidazole or nifurtimox-eflornithine combination therapy (NECT), success at 18 months was noted in 91% of patients treated with fexinidazole versus 98% of patients treated with NECT.[12]

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.

Treatment of asymptomatic carriers is possible, and infection can be detected by means of the card agglutination test for trypanosomiasis (CATT) or lymph node aspiration and confirmed with smears.

Consultations

An infectious disease specialist should be consulted for evaluation of both early- and late-stage African trypanosomiasis in a symptomatic patient with recent travel or suspicious parasitic exposure.

Because African trypanosomiasis is so rarely encountered in the United States, it may be advisable to contact the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, for assistance in the diagnosis and treatment of this disease (Division of Parasitic Diseases, 770-488-7760; Drug Service, 404-639-3670).

Long-Term Monitoring

In both early- and late-stage trypanosomiasis, symptoms usually resolve after treatment, and the parasitemia clears on repeat blood smears.

Patients who have recovered from late-stage East African trypanosomiasis should undergo lumbar punctures every 3 months for the first year. Patients who have recovered from West African trypanosomiasis should undergo lumbar punctures every 6 months for 2 years.

If symptoms return, the CSF WBC count is higher than 20/µL, or trypanosomes are still present in blood or CSF, a relapse is suggested. However, a persistently elevated CSF WBC count may also be observed in recovering patients; thus, the change (increase or decrease) in the WBC count is more diagnostically helpful than the count by itself. If a relapse is noted, repeat treatment with melarsoprol or eflornithine may be considered.

Medication Summary

The type of drug treatment used depends on the type and stage of African trypanosomiasis (sleeping sickness)—that is, whether it is East African or West African and whether it is stage 1 (early/hemolymphatic) or stage 2 (late/neurologic).

Suramin

Clinical Context:  Suramin is an antiparasitic agent given intravenously (IV) in early-stage African trypanosomiasis and onchocerciasis. It is a polysulfonated naphthylamine derivative of urea. Suramin is trypanocidal and works by inhibiting parasitic enzymes and growth factors. It is highly bound to serum proteins and thus crosses the blood-brain barrier poorly. Serum levels are approximately 100 µg/mL. Suramin is more effective and less toxic than pentamidine. The drug is excreted in the urine at a slow rate.

Melarsoprol

Clinical Context:  Melarsoprol is a CDC anti-infective agent. It is a trivalent arsenical agent used in the late (neurologic) stage of African trypanosomiasis. It is trypanocidal, inhibiting parasitic glycolysis. Melarsoprol is water-insoluble and has a half-life of 35 hours. Serum levels are in the range of 2-5 µg/mL, but CSF levels are 50-fold lower. Melarsoprol is primarily excreted by the kidneys. Clinical improvement is usually observed within 4 days after starting the drug. Parasitemia is cleared in as many as 90-95% of cases. However, the drug can be toxic and even fatal in 4-6% of cases.

Studies have demonstrated the effectiveness of 10-day melarsoprol treatments for late-stage African trypanosomiasis. In addition, melarsoprol resistance has become a concern in the Congo and Uganda; as many as 30% of cases do not respond to the drug.

Eflornithine (Vaniqa)

Clinical Context:  Eflornithine is recommended for treatment of patients with West African trypanosomiasis, especially in the late (neurologic) stage. It is a selective and irreversible inhibitor of ornithine decarboxylase, which is a critical enzyme for DNA and RNA synthesis. It is used for patients in whom melarsoprol fails and is generally better tolerated and less toxic than arsenic drugs. The initial response time is 1-2 weeks. Eflornithine is available via the World Health Organization.

Pentamidine isethionate (Pentam)

Clinical Context:  Pentamidine isethionate is an antiprotozoal agent typically used for early (stage 1) African trypanosomiasis, as well as for Pneumocystis carinii pneumonia and leishmaniasis. It works by inhibiting dihydrofolate reductase enzyme, thereby interfering with parasite aerobic glycolysis.

Because of poor gastrointestinal absorption, pentamidine is administered IV or intramuscularly and is strongly bound to tissues, including the spleen, liver, and kidneys. Clinical improvement is usually noted within 24 hours of injection, and a cure rate exceeding 90% has been reported. Pentamidine does not penetrate the blood-brain barrier effectively and thus does not treat central nervous system infection.

Class Summary

Biochemical pathways in the parasite are sufficiently different from those in the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Author

Hazem Alsalman Hnaide, MD, Consulting Physician, Arizona ID Consultants

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD, Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Daniel R Lucey, MD, MPH, MD, MPH,

Disclosure: Nothing to disclose.

Kerry O Cleveland, MD, Professor of Medicine, University of Tennessee College of Medicine; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis

Disclosure: Nothing to disclose.

Kitonga P Kiminyo, MD, Consulting Staff, ID Consultants, Inc

Disclosure: Nothing to disclose.

Randy O Odero, MB, ChB, Infectious Disease Specialist

Disclosure: Nothing to disclose.

Acknowledgements

Gary L Gorby, MD Associate Professor, Departments of Internal Medicine and Medical Microbiology and Immunology, Division of Infectious Diseases, Creighton University School of Medicine; Associate Professor of Medicine, University of Nebraska Medical Center; Associate Chair, Omaha Veterans Affairs Medical Center

Gary L Gorby, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Joseph F John Jr, MD, FACP, FIDSA, FSHEA Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Daniel R Lucey, MD, MPH Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences

Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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African trypanosomiasis (sleeping sickness). Human trypanosomes blood smear.

Trypanosoma life cycle. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).

Trypanosoma brucei in a thin blood smear stained with Giemsa. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).

African trypanosomiasis (sleeping sickness). Human trypanosomes blood smear.

Trypanosoma life cycle. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).

Trypanosoma brucei in a thin blood smear stained with Giemsa. Courtesy of the CDC Division of Parasitic Diseases and Malaria (DPDx at https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html).

Type of Trypanosomiasis Medications
Stage 1 (Early or Hemolymphatic Stage) Stage 2 (Late or Neurologic Stage)
East African trypanosomiasis (caused by Trypanosoma brucei rhodesiense)Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21Melarsoprol 2-3.6 mg/kg/day IV for 3 days; after 1 week, 3.6 mg/kg/day for 3 days; after 10-21 days, repeat cycle
West African trypanosomiasis (caused by Trypanosoma brucei gambiense)Pentamidine isethionate 4 mg/kg/day IM for 10 days



or



Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21



Nifurtimox-eflornithine combination therapy (NECT): Nifurtimox 5 mg/kg PO q8h for 10 days and eflornithine 200 mg/kg IV q12h for 7 days



or



Eflornithine 400 mg/kg/day IV in 2 divided doses for 14 days



or



Melarsoprol IV for 10 days