African trypanosomiasis medical therapy: Difference between revisions

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* (old "standard" 26-day melarsoprol therapy) Intravenous melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously for 3 days, with 7-day breaks between the series) (this regimen is less convenient and patients are less likely to complete therapy)<ref name="Pepin2006">{{cite journal | author=Pepin J, Mpia B | title=Randomized controlled trial of three regimens of melarsoprol in the treatment of ''Trypanosoma brucei gambiense'' trypanosomiasis | journal=Trans R Soc Trop Med Hyg | year=2006 | volume=100 | pages=437&ndash;41 | id=PMID 16483622 }}</ref>;
* (old "standard" 26-day melarsoprol therapy) Intravenous melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously for 3 days, with 7-day breaks between the series) (this regimen is less convenient and patients are less likely to complete therapy)<ref name="Pepin2006">{{cite journal | author=Pepin J, Mpia B | title=Randomized controlled trial of three regimens of melarsoprol in the treatment of ''Trypanosoma brucei gambiense'' trypanosomiasis | journal=Trans R Soc Trop Med Hyg | year=2006 | volume=100 | pages=437&ndash;41 | id=PMID 16483622 }}</ref>;
* (incremental melarsoprol therapy) 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3–10) (previously thought to reduce the risk of treatment-induced encephalopathy, but now known to be associated with an increased risk of relapse and a higher incidence of encephalopathy)<ref name="Bisser2007"/><ref name="Pepin2006"/>;
* (incremental melarsoprol therapy) 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3–10) (previously thought to reduce the risk of treatment-induced encephalopathy, but now known to be associated with an increased risk of relapse and a higher incidence of encephalopathy)<ref name="Bisser2007"/><ref name="Pepin2006"/>;
===Antimicrobial Regimen===
:* ''' Sleeping sickness'''<ref>{{cite web|title=African Trypanosomiasis| url=  http://www.cdc.gov/parasites/sleepingsickness/health_professionals/index.html}}</ref> 
::* 1. '''East african trypanosomiasis'''
:::* 1.1 '''T. b. rhodesiense, hemolymphatic stage'''
::::* 1.1.1 '''Adult '''
:::::* Preferred regimen: [[Suramin]] 1 gm IV on days 1,3,5,14, and 21
::::* 1.1.2 '''Pediatric'''
:::::* Preferred regimen: [[Suramin]] 20 mg/kg IV on days 1, 3, 5, 14, and 21
:::* 1.2 '''T. b. rhodesiense, CNS involvement'''
::::* 1.2.1 '''Adult'''
:::::* Preferred regimen: [[Melarsoprol]] 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
::::* 1.2.2 '''Pediatric'''
:::::* Preferred regimen: [[Melarsoprol]] 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days
::* 2. '''West african trypanosomiasis'''
:::* 2.1 '''T. b. gambiense, hemolymphatic stage'''
::::* 2.1.1 '''Adult'''
:::::* Preferred regimen: [[Pentamidine]] 4 mg/kg/day IM/ IV for 7-10 days
::::* 2.1.2 '''Pediatric'''
:::::* Preferred regimen: [[Pentamidine]] 4 mg/kg/day IM/IV for 7-10 days
:::::* Note (1): Pentamidine should be used during pregnancy and lacation  only if the potential benefit justifies the potential risk
:::::* Note (2): IM/IV Pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
:::* 2.2  '''T. b. gambiense, CNS involvement'''
::::* 2.2.1 '''Adult'''
:::::* Preferred regimen: [[Eflornithine]] 400 mg/kg/day  IV qid for 14 days
::::* 2.2.2 '''Pediatric'''
:::::* Preferred regimen: [[Eflornithine]] 400 mg/kg/day IV  qid for 14 days
:::::* Note (1): [[Eflornithine]] should be used during pregnancy and lactation, only if the potential benefit justifies the potential risk
:::::* Note (2): The safety of [[Eflornithine]] in children has not been established. Eflornithine is not approved by the Food and Drug Administration (FDA) for use in pediatric patients. [[Eflornithine]] is listed for the treatment of 1st stage African trypanosomiasis inTrypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.


==References==
==References==

Revision as of 20:34, 28 July 2015

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

Overview

Medical treatment of African trypanosomiasis should begin as soon as possible and is based on the infected person’s symptoms and laboratory results. Medication for the treatment of African trypanosomiasis is available through the CDC. Pentamidine isethionate and suramin (under an investigational New Drug Protocol from the CDC Drug Service) 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 T.b. gambiense or T. b. rhodiense).

Hospitalization for treatment is necessary. 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.

Medical Therapy

Pharmacotherapy

Pentamidine isethionate and suramin (under an investigational New Drug Protocol from the CDC Drug Service) 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 T.b. gambiense or T. b. rhodiense).

According to a treatment study of Trypanosoma gambiense caused human African trypanosomiasis, use of eflornithine (DMFO) resulted in fewer adverse events than treatment with melaroprol. [1]

All patients should be followed up for two years with lumbar punctures every six months to look for relapse.

Standard Treatment

The current standard treatment for first stage disease is:

The current standard treatment for second stage (late stage) disease is:

Alternative Therapies

Alternative first line therapies include:

  • Intravenous melarsoprol 0.6 mg/kg on day 1, 1.2 mg/kg iv melarsoprol on day 2, and 1.2 mg/kg/day iv melarsoprol combined with oral 7.5 mg/kg nifurtimox twice a day on days 3 to 10;[4] or
  • Intravenous eflornithine 50 mg/kd every six hours for 14 days.[5]

In areas with melarsoprol resistance or in patients who have relapsed after melarsoprol monotherapy, the treatment should be:

  • melarsoprol and nifurtimox, or
  • eflornithine

Out-Dated Therapies

The following traditional regimens should no longer be used:

  • (old "standard" 26-day melarsoprol therapy) Intravenous melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously for 3 days, with 7-day breaks between the series) (this regimen is less convenient and patients are less likely to complete therapy)[6];
  • (incremental melarsoprol therapy) 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3–10) (previously thought to reduce the risk of treatment-induced encephalopathy, but now known to be associated with an increased risk of relapse and a higher incidence of encephalopathy)[4][6];

Antimicrobial Regimen

  • Sleeping sickness[7]
  • 1. East african trypanosomiasis
  • 1.1 T. b. rhodesiense, hemolymphatic stage
  • 1.1.1 Adult
  • Preferred regimen: Suramin 1 gm IV on days 1,3,5,14, and 21
  • 1.1.2 Pediatric
  • Preferred regimen: Suramin 20 mg/kg IV on days 1, 3, 5, 14, and 21
  • 1.2 T. b. rhodesiense, CNS involvement
  • 1.2.1 Adult
  • Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
  • 1.2.2 Pediatric
  • Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days
  • 2. West african trypanosomiasis
  • 2.1 T. b. gambiense, hemolymphatic stage
  • 2.1.1 Adult
  • Preferred regimen: Pentamidine 4 mg/kg/day IM/ IV for 7-10 days
  • 2.1.2 Pediatric
  • Preferred regimen: Pentamidine 4 mg/kg/day IM/IV for 7-10 days
  • Note (1): Pentamidine should be used during pregnancy and lacation only if the potential benefit justifies the potential risk
  • Note (2): IM/IV Pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
  • 2.2 T. b. gambiense, CNS involvement
  • 2.2.1 Adult
  • Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days
  • 2.2.2 Pediatric
  • Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days
  • Note (1): Eflornithine should be used during pregnancy and lactation, only if the potential benefit justifies the potential risk
  • Note (2): The safety of Eflornithine in children has not been established. Eflornithine is not approved by the Food and Drug Administration (FDA) for use in pediatric patients. Eflornithine is listed for the treatment of 1st stage African trypanosomiasis inTrypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.

References

  1. ↑ 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.
  2. ↑ http://www.cdc.gov/ncidod/dpd/parasites/trypanosomiasis/factsht_ea_trypanosomiasis.htm#what http://www.cdc.gov/ncidod/dpd/parasites/trypanosomiasis/factsht_wa_trypanosomiasis.htm#Top http://www.dpd.cdc.gov/dpdx/HTML/TrypanosomiasisAfrican.htm
  3. ↑ "Efficacy of new, concise schedule for melarsoprol in treatment of sleeping sickness caused by Trypanosoma brucei gambiense: a randomised trial". Lancet. 355 (9213): 1419&ndash, 25. 2000. PMID 10791526. Text " Burri C, Nkunku S, Merolle A, et al. " ignored (help)
  4. ↑ 4.0 4.1 Bisser S, N'Siesi F-X, Lejon V; et al. (2007). J Infect Dis. 195: 322&ndash, 29 http://www.journals.uchicago.edu/JID/journal/issues/v195n3/36827/36827.html. Missing or empty |title= (help)
  5. ↑ van Nieuwenhove S, Schechter PJ, Declercq J; et al. (1985). "Treatment of gambiense sleeping sickness in the Sudan with oral DFMO (DL-alfa-difluoromethyl ornithine) an inhibitor of ornithine decarboxylase: first field trial". Trans R Soc Trop Med Hyg. 79 (5): 692&ndash, 8.
  6. ↑ 6.0 6.1 Pepin J, Mpia B (2006). "Randomized controlled trial of three regimens of melarsoprol in the treatment of Trypanosoma brucei gambiense trypanosomiasis". Trans R Soc Trop Med Hyg. 100: 437&ndash, 41. PMID 16483622.
  7. ↑ "African Trypanosomiasis".
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