African Trypanosomiasis (Sleeping Sickness)


Article Author:
Noel Dunn


Article Editor:
Rotimi Adigun


Editors In Chief:
Marlon Bayot
John Sanchez
Bruce Blanchard


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Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
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Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
12/14/2018 1:01:23 PM

Introduction

African trypanosomiasis, also known as human African trypanosomiasis (HAT) and sleeping sickness, is caused by 1 of 2 Trypanosoma brucei protozoa transmitted by the tsetse fly in sub-Saharan Africa. The disease is considered a neglected tropical disease and remains a nearly universal fatal disease if not treated.[1][2][3]

Etiology

Trypanosoma brucei is usually transmitted to humans from an infected tsetse fly.[4]

Epidemiology

HAT Trypanosoma brucei gambiense is a disease endemic to western sub-Saharan Africa, while HAT Trypanosoma brucei rhodesiense affects areas of eastern sub-Saharan Africa. As the 2 diseases are spread by different tsetse subspecies, the 2 diseases do not overlap, though Uganda has both variants within its borders. Estimates of the disease prevalence have proven to be difficult, though some studies estimate 20,000 individuals are affected by the disease, with nearly 9100 dying from both variants in 2010.

African trypanosomiasis can occur at any age and can affect all races.[5]

Pathophysiology

Once the tsetse fly ingests the trypanosomes, they multiply and develop into epimastigotes. Humans are infected after the bite from a tsetse fly. The injected parasites then rapidly divide in the bloodstream and lymphatics. Eventually, the parasite enters the central nervous system (CNS) and causes neurological and behavioral symptoms.

The trypanosomes evade the host's immune system because of extensive antigenic variation of the glycoproteins located on the surface of the parasite. During this time, the parasites invade almost every organ in the body.

Some individuals may develop a severe hypersensitivity reaction to the parasite that leads to itching, swelling, and edema.

In the liver, there may be portal infiltration and fatty degeneration.

When the heart is invaded, arrhythmias may develop leading to death.

When the brain is involved, it may lead to meningoencephalitis, bleeding, edema, and granulomatous lesions.

History and Physical

HAT Trypanosoma brucei gambiense

The initial stage often presents with a painless eschar at the point of infection, though this is often not recalled due to a prolonged asymptomatic course. Patients often have an indolent first stage marked by posterior cervical lymphadenopathy (Winterbottom’s sign), headaches, malaise, and arthralgias. As the disease progresses to the second stage, patients will develop somnolence, fatigue, neurological deficits, tremors, ataxia, seizures, comas, and eventually death.

HAT Trypanosoma brucei rhodesiense

Affected individuals typically present after inoculation with a painful eschar and a rapidly progressing illness marked by fevers, rash, fatigue, and myalgias. Within a few weeks to months, the disease progresses to the second stage, with symptoms identical to that of HAT Trypanosoma brucei gambiense but with a much-accelerated course that quickly leads to death.

Physical Findings

  • Induration at the bite site
  • In light-skinned individuals, one may see skin lesions (trypanids)
  • Generalized lymphadenopathy which is most prominent in the axilla and inguinal area.
  • Fever
  • Tachycardia
  • Edema
  • Splenomegaly
  • Disorientation and altered mental status
  • Psychosis
  • Stupor and coma

Evaluation

HAT Trypanosoma brucei gambiense can be screened for with the card agglutination trypanosoma test (CATT), a study that examines serum for antigen and that carries a sensitivity of 91% and specificity of 97%. Both species can also be identified with Giemsa-stained blood, lymph node aspirates, and cerebrospinal fluid (CSF) fluid. All patients with suspected HAT should be screened for CNS involvement with a lumbar puncture; CSF fluid should be tested for trypanosomes, leukocytosis, and trypanosome IgM.  In the second-stage infections, the number of parasites in congestive heart failure (CHF) can be very low. World Health Organization (WHO) diagnostic criteria for suspected second stage trypanosomiasis, therefore, consists of either the presence of trypanosomes in CSF fluid or greater than 5 white blood cells (WBCs) per microliter of fluid in a suspected case.

In many hospitals, in Africa, a blood smear is often done as it will reveal the mobile trypanosomes. Blood smears are often positive in early disease when the number of circulating parasites is very high.

Lymph node aspiration is sometimes done to identify the parasite and may yield positive results.

CT scan and MRI of the brain frequently reveal massive cerebral edema and enhancement of the white matter.

Treatment / Management

The early stage management requires treatment of fever and malaise. Close monitoring of the CNS status is necessary. Sometimes, patients may require intubation and mechanical ventilation as they can not maintain a patent airway.[6][7][8]

HAT Trypanosoma brucei gambiense: Treatment during the first stage consists of pentamidine. After patients develop CNS symptoms, patients will require eflornithine and nifurtimox. If no response is achieved, providers may resort to melarsoprol.

HAT Trypanosoma brucei rhodesiense: Treatment of the initial stage consists of suramin while treatment of the second stage consists of melarsoprol.

Most studies today show that combination therapy with melarsoprol and nifurtimox is more effective than either solo therapy.

Prognosis

If the infection is treated during the early stage, recovery is possible in most patients. However, if the patient presents with stage 2 disease, the CNS involvement usually is fatal. Today, the cure rate with the drug melarsoprol is more than 90%.[9]

Complications

  • Severe wasting
  • Anemia
  • Fatigue
  • Stupor
  • Psychosis
  • Aspiration pneumonitis
  • Death

Postoperative and Rehabilitation Care

  • Patients need long-term monitoring to ensure they have not developed any complications.
  • The patients should be followed up with regular blood smears and lumbar puncture every three months for the first 12 months and then at six monthly intervals.
  • If relapse is noted, then repeat treatment with melarsoprol is needed.
  • Side effects of melarsoprol include hypertension, encephalopathy, neuropathy, cardiac damage, and vomiting.
  • Side effects of suramin include emesis, neuropathy, kidney damage and blood dyscrasias.
  • Side effects of eflornithine include pancytopenia, seizures, and hearing impairment.
  • Because of these severe side effects, patients need to be closely monitored and the dose adjusted or discontinued.

Consultations

If a patient is suspected of having African trypanosomiasis, immediate consultation with an infectious disease expert is recommended.

If the patient is in the United States, one should contact the Centers for Disease Control and Prevention (CDC).

Deterrence and Patient Education

  • There is no vaccine yet available.
  • Tourists should avoid travel to endemic areas and avoid wearing dark contrasting colors.
  • The tsetse fly is not affected by any insect repellant.

Pearls and Other Issues

Melarsoprol is an arsenical compound that must be administered in propylene glycol. Administration of the drug is painful and carries multiple adverse effects, the most serious consisting of the melarsoprol-induced encephalopathic syndrome. This occurs in 1.5% to 28% of treatments and results in nearly a 50% mortality rate. All patients receiving the medication should, therefore, be monitored in a hospital setting.

Enhancing Healthcare Team Outcomes

African trypanosomiasis, also known as human African trypanosomiasis (HAT) and sleeping sickness, is caused by 1 of 2 Trypanosoma brucei protozoa transmitted by the tsetse fly in sub-Saharan Africa. The disease is considered a neglected tropical disease and remains a nearly universal fatal disease if not treated. However, most healthcare workers in North America are unlikely to see a case in their lifetime. But it is still important to consider this disorder in the differential in a patient coming from the tropics. The best advice is to immediately consult with infectious disease on how to make the diagnosis and manage the patient.


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African Trypanosomiasis (Sleeping Sickness) - Questions

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A patient from eastern Africa presents with a headache, nausea, and vomiting. He has difficulty in his gait and a lumbar puncture reveals trypanosomiasis. What is the drug of choice for this patient?



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A 53-year old male presents to the emergency department after having a 2-day history of fevers, joint pain, and malaise. His wife reports that he sometimes seems to be confused over the last day. He states that he returned from Tanzania 4 days ago where he was on a safari. He had multiple insect bites but is adamant that he took atovaquone/proguanil as malarial prophylaxis. The patient has a history of hypertension but is otherwise healthy and denies any surgeries. He is only currently taking hydrochlorothiazide, atovaquone/proguanil, and primaquine. On physical examination, the patient has a fever to 101.3 F, heart rate of 89 beats per minute, blood pressure of 123/85 mmHg, respiratory rate of 18, and SpO2 of 99% on room air. He is alert and oriented to person, place, and time but must often be reoriented. Physical examination is benign with no focal neurological deficits or neck stiffness. Multiple insect bites are noted on his upper extremities with a chancre on his right, upper arm. A CBC shows a white blood cell count of 14,000 with a 10.2% eosinophil predominance. Malaria rapid diagnostic test, thick smear, and thin smear are negative. What is the next best step?



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African Trypanosomiasis (Sleeping Sickness) - References

References

Franco JR,Cecchi G,Priotto G,Paone M,Diarra A,Grout L,Simarro PP,Zhao W,Argaw D, Monitoring the elimination of human African trypanosomiasis: Update to 2016. PLoS neglected tropical diseases. 2018 Dec     [PubMed]
Barrett MP, The elimination of human African trypanosomiasis is in sight: Report from the third WHO stakeholders meeting on elimination of gambiense human African trypanosomiasis. PLoS neglected tropical diseases. 2018 Dec     [PubMed]
Bentley SJ,Jamabo M,Boshoff A, The Hsp70/J-protein machinery of the African trypanosome, Trypanosoma brucei. Cell stress     [PubMed]
Saarman NP,Opiro R,Hyseni C,Echodu R,Opiyo EA,Dion K,Johnson T,Aksoy S,Caccone A, The population genomics of multiple tsetse fly (Glossina fuscipes fuscipes) admixture zones in Uganda. Molecular ecology. 2018 Nov 24     [PubMed]
Kame-Ngasse GI,Njiokou F,Melachio-Tanekou TT,Farikou O,Simo G,Geiger A, Prevalence of symbionts and trypanosome infections in tsetse flies of two villages of the     [PubMed]
Ferrins L,Sharma A,Thomas SM,Mehta N,Erath J,Tanghe S,Leed SE,Rodriguez A,Mensa-Wilmot K,Sciotti RJ,Gillingwater K,Pollastri MP, Anilinoquinoline based inhibitors of trypanosomatid proliferation. PLoS neglected tropical diseases. 2018 Nov     [PubMed]
Merritt MW,Sutherland CS,Tediosi F, Ethical Considerations for Global Health Decision-Making: Justice-Enhanced Cost-Effectiveness Analysis of New Technologies for {i}Trypanosoma brucei gambiense{/i}. Public health ethics. 2018 Nov     [PubMed]
Tarawneh AH,Al-Momani LAA,León F,Jain SK,Gadetskaya AV,Abu-Orabi ST,Tekwani BL,Cutler SJ, Evaluation of Triazole and Isoxazole Derivatives as Potential Anti-infective Agents. Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents. 2018 Apr     [PubMed]
Kazumba LM,Kaka JT,Ngoyi DM,Tshala-Katumbay D, Mortality trends and risk factors in advanced stage-2 Human African Trypanosomiasis: A critical appraisal of 23 years of experience in the Democratic Republic of Congo. PLoS neglected tropical diseases. 2018 Jun     [PubMed]

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