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{{African trypanosomiasis}} | {{African trypanosomiasis}} | ||
{{CMG}} | {{CMG}}; {{AOEIC}} Pilar Almonacid, {{ADG}} | ||
==Overview== | ==Overview== | ||
'''Sleeping sickness''' or '''African trypanosomiasis''' is a [[parasitic]] [[disease]] of people and animals caused by [[protozoa]] of the genus ''[[Trypanosoma]]'' and transmitted by the [[tsetse fly|'''tsetse fly''']]. The disease is [[Endemic (epidemiology)|endemic]] to 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|''Trypanosoma brucei rhodesiense'']] or [[Trypanosoma brucei gambiense|''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.<ref>{{cite paper | |||
|author=WHO Media centre | |||
|title=Fact sheet N°259: African trypanosomiasis or sleeping sickness | |||
|date=2001 | |||
|url=http://www.who.int/mediacentre/factsheets/fs259/en/index.html | |||
}}</ref> | |||
==Classification== | |||
African trypanosomiasis can be classified based upon the [[pathogen]] and [[Geographical pole|geographic location]] into two types, [[Trypanosomiasis, east-African|East African trypanosomiasis]] and [[Trypanosomiasis, west African|West African trypanosomiasis]].<ref name="pmid16308383">{{cite journal |vauthors=Picozzi K, Fèvre EM, Odiit M, Carrington M, Eisler MC, Maudlin I, Welburn SC |title=Sleeping sickness in Uganda: a thin line between two fatal diseases |journal=BMJ |volume=331 |issue=7527 |pages=1238–41 |year=2005 |pmid=16308383 |pmc=1289320 |doi=10.1136/bmj.331.7527.1238 |url=}}</ref> | |||
==Pathophysiology== | |||
African trypanosomiasis is a human tropical parasitic disease usually caused by [[protozoan]] hemo-flagellates belonging to the complex [[Trypanosoma brucei|''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 hemo-lymphatic stage with symptoms including [[fever]], [[lymphadenopathy]], and [[pruritus]]. In the [[Meningoencephalitis|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 [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] than [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']]. Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] and months to years for [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']]. | |||
==Causes== | |||
African trypanosomiasis is a human tropical [[parasitic]] [[disease]] usually caused by [[protozoan]] hemo-flagellates belonging to the complex ''[[Trypanosoma brucei]]''. Two [[subspecies]] that are [[Morphology (biology)|morphologically]] indistinguishable cause distinct [[disease]] patterns in humans: [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']] causes [[African trypanosomiasis|West African sleeping sickness]] and [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] causes [[East African sleeping sickness]]. | |||
==Differentiating African trypanosomiasis from other diseases== | |||
The hemo-lymphatic stage of [[African trypanosomiasis]] presents with a [[rash]], [[fever]], and [[anemia]] and must be differentiated from other diseases such as [[brucellosis]], [[typhoid fever]], [[malaria]], [[tuberculosis]], [[lymphoma]], [[dengue]], and [[leptospirosis]]. The most prominent symptoms in the [[neurological]] stage of [[African trypanosomiasis]] are [[Altered mental status|mental status changes]] and [[sleep disturbances]], so [[Differential diagnosis|differential diagnoses]] include [[CNS]] [[TB|tuberculosis]], [[meningitis]], and [[HIV]]-related [[Opportunistic infection|opportunistic infections]], including [[Cryptococcal Meningitis|cryptococcal meningitis]].<ref name="pmid1593042322">{{cite journal|author=Pappas G, Akritidis N, Bosilkovski M, Tsianos E|title=Brucellosis.|journal=N Engl J Med|year=2005|volume=352|issue=22|pages=2325-36|pmid=15930423|doi=10.1056/NEJMra050570|pmc=|url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15930423}}</ref><ref>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</ref><ref name="pmid754636422">{{cite journal|year=1995|title=Brucellosis: current epidemiology, diagnosis, and management.|url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7546364|journal=Curr Clin Top Infect Dis|volume=15|issue=|pages=115-28|doi=|pmc=|pmid=7546364|author=Young EJ}}</ref><ref name="enf22">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</ref> | |||
==Epidemiology and Demographics== | |||
Currently, it is estimated that the annual prevalence of [[African trypanosomiasis]] is less than 20,000. In 2014, 3,796 cases of sleeping sickness were reported to the World Health Organization and [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']] accounted for >98% of cases. There is no age predilection for [[African trypanosomiasis]] disease.<ref name="pmid16735165">{{cite journal |vauthors=Fèvre EM, Picozzi K, Jannin J, Welburn SC, Maudlin I |title=Human African trypanosomiasis: Epidemiology and control |journal=Adv. Parasitol. |volume=61 |issue= |pages=167–221 |year=2006 |pmid=16735165 |doi=10.1016/S0065-308X(05)61005-6 |url=}}</ref><ref name="pmid25125985">{{cite journal |vauthors=Franco JR, Simarro PP, Diarra A, Jannin JG |title=Epidemiology of human African trypanosomiasis |journal=Clin Epidemiol |volume=6 |issue= |pages=257–75 |year=2014 |pmid=25125985 |pmc=4130665 |doi=10.2147/CLEP.S39728 |url=}}</ref><ref name="urlTrypanosomiasis, African (Sleeping Sickness) - Chapter 3 - 2018 Yellow Book | Travelers Health | CDC">{{cite web |url=https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/trypanosomiasis-african-sleeping-sickness |title=Trypanosomiasis, African (Sleeping Sickness) - Chapter 3 - 2018 Yellow Book | Travelers' Health | CDC |format= |work= |accessdate=}}</ref><ref name="urlWHO | The current situation">{{cite web |url=http://www.who.int/trypanosomiasis_african/country/country_situation/en/ |title=WHO | The current situation |format= |work= |accessdate=}}</ref> | |||
==Risk Factors== | |||
Risk factors for [[African trypanosomiasis]] include residence in Central or South America, living in old houses with mud and stick wall constructions or straw roofs, ingestion of contaminated water, or receiving [[blood transfusions]] or [[organ donation]] from individuals in regions with high [[Endemic|endemicity]]. The risk of [[infection]] increases with the number of times a person is bitten by the [[Tsetse fly|tsetse fly.]] The [[neonatal]] risk is highest among those who [[Breastfeeding|breastfeed]] from [[bleeding]] or cracked nipples of infected mothers and infants who are delivered from [[seropositive]] mothers with active [[disease]]. | |||
==Natural History, Complications and Prognosis== | |||
If [[African trypanosomiasis]] is left untreated, the patient will develop symptoms of progressive [[Altered mental status|mental deterioration]], which is irreversible and eventually leads to death. Common complications that can develop as a result of [[African trypanosomiasis]] include [[anemia]], [[aspiration pneumonia]], [[meningoencephalitis]], [[Seizure|seizures]], [[coma]], [[perinatal death]], or [[abortion]] ([[congenital]] infection). The prognosis of [[African trypanosomiasis]] is good with treatment. Without treatment, the mortality rate of [[African trypanosomiasis|African sleeping sickness]] is close to 100%.<ref name="pmid16157286">{{cite journal |vauthors=Blum J, Schmid C, Burri C |title=Clinical aspects of 2541 patients with second stage human African trypanosomiasis |journal=Acta Trop. |volume=97 |issue=1 |pages=55–64 |year=2006 |pmid=16157286 |doi=10.1016/j.actatropica.2005.08.001 |url=}}</ref><ref name="pmid338269">{{cite journal |vauthors=Levine IM, Jossmann PB, DeAngelis V |title=Liorseal, a new muscle relaxant in the treatment of spasticity--a double-blind quantitative evaluation |journal=Dis Nerv Syst |volume=38 |issue=12 |pages=1011–5 |year=1977 |pmid=338269 |doi= |url=}}</ref> | |||
==Diagnosis== | |||
===History and Symptoms=== | |||
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|''Trypanosoma brucei rhodesiense'']] or [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']]) is causing the infection. However, [[infection]] with either form will eventually lead to [[coma]] and death if not treated.<ref name="pmid19833383">{{cite journal |vauthors=Brun R, Blum J, Chappuis F, Burri C |title=Human African trypanosomiasis |journal=Lancet |volume=375 |issue=9709 |pages=148–59 |year=2010 |pmid=19833383 |doi=10.1016/S0140-6736(09)60829-1 |url=}}</ref><ref name="pmid17582444">{{cite journal |vauthors=Masocha W, Rottenberg ME, Kristensson K |title=Migration of African trypanosomes across the blood-brain barrier |journal=Physiol. Behav. |volume=92 |issue=1-2 |pages=110–4 |year=2007 |pmid=17582444 |doi=10.1016/j.physbeh.2007.05.045 |url=}}</ref><ref name="pmid18261232">{{cite journal |vauthors=Checchi F, Filipe JA, Haydon DT, Chandramohan D, Chappuis F |title=Estimates of the duration of the early and late stage of gambiense sleeping sickness |journal=BMC Infect. Dis. |volume=8 |issue= |pages=16 |year=2008 |pmid=18261232 |pmc=2259357 |doi=10.1186/1471-2334-8-16 |url=}}</ref><ref name="pmid9557424">{{cite journal |vauthors=Odiit M, Kansiime F, Enyaru JC |title=Duration of symptoms and case fatality of sleeping sickness caused by Trypanosoma brucei rhodesiense in Tororo, Uganda |journal=East Afr Med J |volume=74 |issue=12 |pages=792–5 |year=1997 |pmid=9557424 |doi= |url=}}</ref> | |||
===Physical examination=== | |||
Physical examination findings of [[African trypanosomiasis]] depend upon the stage of the [[disease]]. [[Skin lesions|Skin lesion<nowiki/>s]] are more prominent in stage 1 of the disease; [[neurological]] findings such as [[Altered mental state|altered level of consciousness]] and [[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|blood]], [[bone marrow|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 hemo-lymphatic stages of [[African trypanosomiasis|West]] and [[African trypanosomiasis|East African Trypanosomiasis]], respectively. [[Melarsoprol]] is the drug of choice for late disease with [[central nervous system]] involvement (infections by [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']] or [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']]). Hospitalization is necessary in 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.<ref name="pmid23260189">{{cite journal |vauthors=Kennedy PG |title=Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness) |journal=Lancet Neurol |volume=12 |issue=2 |pages=186–94 |year=2013 |pmid=23260189 |doi=10.1016/S1474-4422(12)70296-X |url=}}</ref><ref name="pmid27072715">{{cite journal |vauthors=Singh Grewal A, Pandita D, Bhardwaj S, Lather V |title=Recent Updates on Development of Drug Molecules for Human African Trypanosomiasis |journal=Curr Top Med Chem |volume=16 |issue=20 |pages=2245–65 |year=2016 |pmid=27072715 |doi= |url=}}</ref><ref name="pmid17160135">{{cite journal |vauthors=Priotto G, Fogg C, Balasegaram M, Erphas O, Louga A, Checchi F, Ghabri S, Piola P |title=Three drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda |journal=PLoS Clin Trials |volume=1 |issue=8 |pages=e39 |year=2006 |pmid=17160135 |pmc=1687208 |doi=10.1371/journal.pctr.0010039 |url=}}</ref><ref name="pmid16080099">{{cite journal |vauthors=Chappuis F, Udayraj N, Stietenroth K, Meussen A, Bovier PA |title=Eflornithine is safer than melarsoprol for the treatment of second-stage Trypanosoma brucei gambiense human African trypanosomiasis |journal=Clin. Infect. Dis. |volume=41 |issue=5 |pages=748–51 |year=2005 |pmid=16080099 |doi=10.1086/432576 |url=}}</ref> | |||
===Surgery=== | |||
Surgical intervention is not recommended for the management of [[African trypanosomiasis]]. | |||
===Primary Prevention=== | |||
Primary 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 (anatomy)|organ]] and [[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 [[African trypanosomiasis|sleeping sickness]]. | |||
===Secondary Prevention=== | |||
The primary and secondary prevention strategies for [[African trypanosomiasis]] are the same. | |||
==References== | ==References== | ||
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[[Category:Dermatology]] | |||
[[Category:Neurology]] | [[Category:Neurology]] | ||
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[[Category:Infectious disease]] | [[Category:Infectious disease]] | ||
Latest revision as of 20:19, 29 July 2020
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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 of people and animals caused by protozoa of the genus Trypanosoma and transmitted by the tsetse fly. The disease is endemic to 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 protozoan hemo-flagellates 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 hemo-lymphatic stage with symptoms including 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 Trypanosoma brucei rhodesiense than Trypanosoma brucei gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.
Causes
African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemo-flagellates 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 trypanosomiasis presents with a rash, fever, and anemia and must be differentiated from other diseases such as brucellosis, typhoid fever, malaria, tuberculosis, lymphoma, dengue, and leptospirosis. The most prominent symptoms in the neurological stage of African trypanosomiasis are mental status changes and sleep disturbances, so differential diagnoses include CNS tuberculosis, 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 cases of sleeping sickness were reported to the World Health Organization and Trypanosoma brucei gambiense accounted for >98% of cases. There is no age predilection 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 mud and stick wall constructions or straw roofs, ingestion of contaminated water, or receiving blood transfusions or 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 or cracked nipples of infected mothers and infants who are delivered from seropositive mothers with active disease.
Natural History, Complications and Prognosis
If African trypanosomiasis is left untreated, the patient will develop symptoms of progressive mental deterioration, which is irreversible and eventually leads 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 depend upon the stage of the disease. Skin lesions are more prominent in stage 1 of the disease; neurological findings such as altered level of consciousness and 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 hemo-lymphatic stages 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 rhodesiense). Hospitalization is necessary in 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
Primary 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 and 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
- ↑ Template:Cite paper
- ↑ 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.
- ↑ Pappas G, Akritidis N, Bosilkovski M, Tsianos E (2005). "Brucellosis". N Engl J Med. 352 (22): 2325–36. doi:10.1056/NEJMra050570. PMID 15930423.
- ↑ 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
- ↑ Young EJ (1995). "Brucellosis: current epidemiology, diagnosis, and management". Curr Clin Top Infect Dis. 15: 115–28. PMID 7546364.
- ↑ 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
- ↑ 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.
- ↑ 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.
- ↑ "Trypanosomiasis, African (Sleeping Sickness) - Chapter 3 - 2018 Yellow Book | Travelers' Health | CDC".
- ↑ "WHO | The current situation".
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
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- ↑ 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.
- ↑ 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.