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==Overview==
==Overview==
'''Sleeping sickness''' or '''African trypanosomiasis''' is a [[parasitic]] [[disease]] in people and animals, caused by [[protozoa]] of genus ''[[Trypanosoma]]'' and transmitted by the '''[[tsetse fly]]'''. The disease is [[Endemic (epidemiology)|endemic]] in certain regions of Sub-Saharan Africa, covering about 36 countries and 60 million people. The clinical course of human African trypanosomiasis has two stages. In the first stage, the [[Parasites|parasite]] is found in the peripheral circulation, but it has not yet invaded the [[central nervous system]]. Once the [[Parasites|parasite]] crosses the [[blood-brain barrier]] and infects the [[central nervous system]], the [[disease]] enters the second stage. The [[subspecies]] that cause African trypanosomiasis have different rates of [[disease]] progression, and the clinical features depend on which form of the [[Parasites|parasite]] (Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense) is causing the [[infection]]. However, [[infection]] with either form will eventually lead to [[coma]] and death if not treated.
'''Sleeping sickness''' or '''African trypanosomiasis''' is a [[parasitic]] [[disease]] in people and animals, caused by [[protozoa]] of genus ''[[Trypanosoma]]'' and transmitted by the '''[[tsetse fly]]'''. The disease is [[Endemic (epidemiology)|endemic]] in certain regions of Sub-Saharan Africa, covering about 36 countries and 60 million people. The clinical course of human African trypanosomiasis has two stages. In the first stage, the [[Parasites|parasite]] is found in the peripheral circulation but it has not yet invaded the [[central nervous system]]. Once the [[Parasites|parasite]] crosses the [[blood-brain barrier]] and infects the [[central nervous system]], the [[disease]] enters the second stage. The [[subspecies]] that cause African trypanosomiasis have different rates of [[disease]] progression, and the clinical features depend on which form of the [[Parasites|parasite]] (Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense) is causing the [[infection]]. However, [[infection]] with either form will eventually lead to [[coma]] and death if not treated.


==Historical Perspective==
==Historical Perspective==

Revision as of 16:51, 25 July 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid ; Aditya Ganti M.B.B.S. [2]

Overview

Sleeping sickness or African trypanosomiasis is a parasitic disease in people and animals, caused by protozoa of genus Trypanosoma and transmitted by the tsetse fly. The disease is endemic in certain regions of Sub-Saharan Africa, covering about 36 countries and 60 million people. The clinical course of human African trypanosomiasis has two stages. In the first stage, the parasite is found in the peripheral circulation but it has not yet invaded the central nervous system. Once the parasite crosses the blood-brain barrier and infects the central nervous system, the disease enters the second stage. The subspecies that cause African trypanosomiasis have different rates of disease progression, and the clinical features depend on which form of the parasite (Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense) is causing the infection. However, infection with either form will eventually lead to coma and death if not treated.

Historical Perspective

African trypanosomiasis has been present in Africa for thousands of years. In 1903, David Bruce identified the causative agent vector. In 1910, the differentiation between the subspecies of the protozoa was established. [1]

Classification

African trypanosomiasis can be classified based upon the pathogen and geographic location into two types East African trypanosomiasis and West African trypanosomiasis.[2]

Pathophysiology

African trypanosomiasis is a human tropical parasitic disease usually caused by a protozoan hemoflagellates belonging to the complex Trypanosoma brucei. Infection is usually transmitted via the tsetse fly bite to the human host. A trypanosomal chancre develops on the site of inoculation. This is followed by a hemolymphatic stage with symptoms that include fever, lymphadenopathy, and pruritus. In the meningoencephalitic stage, invasion of the central nervous system can cause headaches, somnolence, abnormal behavior, and lead to loss of consciousness and coma. The course of infection is much more acute with T. b. rhodesiense than T. b. gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for T. b. rhodesiense and months to years for T. b. gambiense.

Causes

African trypanosomiasis is a human tropical parasitic disease usually caused by a protozoan hemoflagellates belonging to the complex Trypanosoma brucei. Two subspecies that are morphologically indistinguishable cause distinct disease patterns in humans: Trypanosoma brucei gambiense causes West African sleeping sickness and Trypanosoma brucei rhodesiense causes East African sleeping sickness.

Differentiating African trypanosomiasis from other diseases

The hemo-lymphatic stage of African trympnosomiasis presents with a rash, fever, and anemia and must be differentiated with other diseases such as brucellosis, typhoid fever, malaria, tuberculosis, lymphoma, Dengue, Leptospirosis. The Most prominent symptom in the neurological stage of African trypanosomiasis is mental status changes and sleep disturbances, differential diagnoses in CNS TB, meningitis, and HIV-related opportunistic infections, including cryptococcal meningitis.[3][4][5][6]

Epidemiology and Demographics

Currently, it is estimated that the annual prevalence of African trypanosomiasis is less than 20,000. In 2014, 3,796 sleeping sickness cases were reported to the World Health Organization and Trypanosoma brucei gambiense accounted for >98% of cases. There is no age predominance for African trypanosomiasis disease.[7][8][9][10]

Risk Factors

Risk factors for African trypanosomiasis include residence in Central or South America, living in old houses with either mud and sticks wall constructions or straw roofs, ingestion of contaminated water, or receiving blood transfusions/organ donation from individuals in regions with high endemicity. The risk of infection increases with the number of times a person is bitten by the tsetse fly. The Neonatal risk is highest among those who breastfeed from bleeding / cracked nipples of infected mothers and infants who are delivered from seropositive mothers with active disease.

Natural History, Complications and Prognosis

If left untreated, the patient will develop symptoms of progressive mental deterioration, which is irreversible and eventually lead to death. Common complications that can develop as a result of African trypanosomiasis include anemia, aspiration pneumonia, meningoencephalitis, seizures, coma, perinatal death or abortion (congenital infection). The prognosis of African trypanosomiasis is good with treatment. Without treatment, the mortality rate of African sleeping sickness is close to 100%.[11][12]

Diagnosis

History and Symptoms

The clinical course of human African trypanosomiasis has two stages. In the first stage, the parasite is found in the peripheral circulation but it has not yet invaded the central nervous system. Once the parasite crosses the blood-brain barrier and infects the central nervous system, the disease enters the second stage. The subspecies that cause African trypanosomiasis have different rates of disease progression, and the clinical features depend on which form of the parasite (Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense is causing the infection. However, infection with either form will eventually lead to coma and death if not treated.[13][14][15][16]

Physical examination

Physical examination findings of African trypanosomiasis depends upon the stage of the disease. Skin lesions are more prominent in stage 1 and neurological findings such as altered level of consciousness along with hemiparesis predominate in stage 2.

Laboratory Findings

The diagnosis of African trypanosomiasis rests upon demonstrating trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, and cerebrospinal fluid in the late stages of infection.

X-ray Findings

There are no x-ray findings associated with African trypanosomiasis.

CT scan Findings

There are no CT scan findings associated with African trypanosomiasis.

MRI Findings

There are no MRI findings associated with African trypanosomiasis.

Ultrasound Findings

There are no ultrasound findings associated with African trypanosomiasis.

Other imaging findings

There are no other imaging findings associated with African trypanosomiasis.

Other Diagnostic Studies

There are no other diagnostic findings for African trypanosomiasis.

Treatment

Medical Therapy

Medical treatment of African trypanosomiasis should begin as soon as possible and is based on the infected person’s symptoms and laboratory results. Medications are the mainstay of treatment for African trypanosomiasis. Pentamidine isethionate and suramin are the drugs of choice to treat the hemolymphatic stage of West and East African Trypanosomiasis, respectively. Melarsoprol is the drug of choice for late disease with central nervous system involvement (infections by Trypanosoma brucei gambiense or Trypanosoma brucei rhodiense). Hospitalization is necessary for the second stage of the disease. Periodic follow-up exams that include a spinal tap are required for 2 years. If a person fails to receive medical treatment for African trypanosomiasis, death will occur within several weeks to months.[17][18][19][20]

Surgery

Surgical intervention is not recommended for the management of African trypanosomiasis.

Primary Prevention

Prevention and control focus on the eradication of the parasitic host, the tsetse fly. Methods of primary prevention of African trypanosomiasis include use of insecticides to control the vector, use of new construction compounds in building walls and roofs, and organ/blood testing prior to donation. Regular active surveillance, involving case detection and treatment, in addition to tsetse fly control, is the backbone of the strategy for control of sleeping sickness.

Secondary Prevention

The primary and secondary prevention strategies for African trypanosomiasis are the same.

References

  1. Template:Cite paper
  2. Picozzi K, Fèvre EM, Odiit M, Carrington M, Eisler MC, Maudlin I, Welburn SC (2005). "Sleeping sickness in Uganda: a thin line between two fatal diseases". BMJ. 331 (7527): 1238–41. doi:10.1136/bmj.331.7527.1238. PMC 1289320. PMID 16308383.
  3. Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). "Brucellosis". N Engl J Med. 352 (22): 2325–36. doi:10.1056/NEJMra050570. PMID 15930423.
  4. Brucellosis "Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo"Harrison's Principles of Internal Medicine, 19e Accessed on January,2017
  5. Young EJ (1995). "Brucellosis: current epidemiology, diagnosis, and management". Curr Clin Top Infect Dis. 15: 115–28. PMID 7546364.
  6. Enfermedades infecciosas: Brucelosis -Diagnóstico de Brucelosis,Guia para el Equipo de Salud. Ministerio de Salud-Argentina. http://www.msal.gob.ar/images/stories/bes/graficos/0000000304cnt-guia-medica-brucelosis.pdf. Accessed on February 2, 2016
  7. Fèvre EM, Picozzi K, Jannin J, Welburn SC, Maudlin I (2006). "Human African trypanosomiasis: Epidemiology and control". Adv. Parasitol. 61: 167–221. doi:10.1016/S0065-308X(05)61005-6. PMID 16735165.
  8. Franco JR, Simarro PP, Diarra A, Jannin JG (2014). "Epidemiology of human African trypanosomiasis". Clin Epidemiol. 6: 257–75. doi:10.2147/CLEP.S39728. PMC 4130665. PMID 25125985.
  9. "Trypanosomiasis, African (Sleeping Sickness) - Chapter 3 - 2018 Yellow Book | Travelers' Health | CDC".
  10. "WHO | The current situation".
  11. Blum J, Schmid C, Burri C (2006). "Clinical aspects of 2541 patients with second stage human African trypanosomiasis". Acta Trop. 97 (1): 55–64. doi:10.1016/j.actatropica.2005.08.001. PMID 16157286.
  12. Levine IM, Jossmann PB, DeAngelis V (1977). "Liorseal, a new muscle relaxant in the treatment of spasticity--a double-blind quantitative evaluation". Dis Nerv Syst. 38 (12): 1011–5. PMID 338269.
  13. Brun R, Blum J, Chappuis F, Burri C (2010). "Human African trypanosomiasis". Lancet. 375 (9709): 148–59. doi:10.1016/S0140-6736(09)60829-1. PMID 19833383.
  14. Masocha W, Rottenberg ME, Kristensson K (2007). "Migration of African trypanosomes across the blood-brain barrier". Physiol. Behav. 92 (1–2): 110–4. doi:10.1016/j.physbeh.2007.05.045. PMID 17582444.
  15. Checchi F, Filipe JA, Haydon DT, Chandramohan D, Chappuis F (2008). "Estimates of the duration of the early and late stage of gambiense sleeping sickness". BMC Infect. Dis. 8: 16. doi:10.1186/1471-2334-8-16. PMC 2259357. PMID 18261232.
  16. Odiit M, Kansiime F, Enyaru JC (1997). "Duration of symptoms and case fatality of sleeping sickness caused by Trypanosoma brucei rhodesiense in Tororo, Uganda". East Afr Med J. 74 (12): 792–5. PMID 9557424.
  17. Kennedy PG (2013). "Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)". Lancet Neurol. 12 (2): 186–94. doi:10.1016/S1474-4422(12)70296-X. PMID 23260189.
  18. Singh Grewal A, Pandita D, Bhardwaj S, Lather V (2016). "Recent Updates on Development of Drug Molecules for Human African Trypanosomiasis". Curr Top Med Chem. 16 (20): 2245–65. PMID 27072715.
  19. Priotto G, Fogg C, Balasegaram M, Erphas O, Louga A, Checchi F, Ghabri S, Piola P (2006). "Three drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda". PLoS Clin Trials. 1 (8): e39. doi:10.1371/journal.pctr.0010039. PMC 1687208. PMID 17160135.
  20. Chappuis F, Udayraj N, Stietenroth K, Meussen A, Bovier PA (2005). "Eflornithine is safer than melarsoprol for the treatment of second-stage Trypanosoma brucei gambiense human African trypanosomiasis". Clin. Infect. Dis. 41 (5): 748–51. doi:10.1086/432576. PMID 16080099.