Human African trypanosomiasis (HAT) is usually considered lethal without treatment, but treatment of the disease is effective. Some rare cases of spontaneous recovery have been reported.[150]Checchi F, Filipe JA, Barrett MP, et al. The natural progression of gambiense sleeping sickness: what is the evidence? PLoS Negl Trop Dis. 2008;2(12):e303.
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0000303
http://www.ncbi.nlm.nih.gov/pubmed/19104656?tool=bestpractice.com
[151]Jamonneau V, Ilboudo H, Kaboré J, et al. Untreated human infections by Trypanosoma brucei gambiense are not 100% fatal. PLoS Negl Trop Dis. 2012;6(6):e1691.
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001691
http://www.ncbi.nlm.nih.gov/pubmed/22720107?tool=bestpractice.com
[152]Bucheton B, MacLeod A, Jamonneau V. Human host determinants influencing the outcome of Trypanosoma brucei gambiense infections. Parasite Immunol. 2011 Aug;33(8):438-47.
http://www.ncbi.nlm.nih.gov/pubmed/21385185?tool=bestpractice.com
Relapses are possible, and their frequency depends on the drug used and differs from one area to another, reaching up to 60% of relapses to melarsoprol in some foci in some areas.[153]Robays J, Nyamowala G, Sese C, et al. High failure rates of melarsoprol for sleeping sickness, Democratic Republic of Congo. Emerg Infect Dis. 2008 Jun;14(6):966-7.
https://wwwnc.cdc.gov/eid/article/14/6/07-1266_article
http://www.ncbi.nlm.nih.gov/pubmed/18507916?tool=bestpractice.com
[154]Legros D, Evans S, Maiso F, et al. Risk factors for treatment failure after melarsoprol for Trypanosoma brucei gambiense trypanosomiasis in Uganda. Trans R Soc Trop Med Hyg. 1999 Jul-Aug;93(4):439-42.
http://www.ncbi.nlm.nih.gov/pubmed/10674099?tool=bestpractice.com
Although there is no test of cure, treatment outcome assessment is recommended, including cerebrospinal fluid (CSF) examination in symptomatic patients.[32]World Health Organization. Guidelines for the treatment of human African trypanosomiasis. Jun 2024 [internet publication].
https://www.who.int/publications/i/item/9789240096035
Reappearance of trypanosomes within 24 months after treatment is considered as a relapse and not a reinfection.[155]World Health Organization. Epidemiology and control of African trypanosomiasis. WHO Technical Report Series 739. 1986 [internet publication].
https://iris.who.int/bitstream/handle/10665/40346/WHO_TRS_739.pdf
For clinical trials, a follow-up period of 18 months is maintained to assess drug efficacy.[156]World Health Organization. Recommendations of the informal consultation on issues for clinical product development for human African trypanosomiasis. Geneva: WHO; 2007.
https://iris.who.int/bitstream/handle/10665/69727/WHO_CDS_NTD_IDM_2007.1_eng.pdf
Nevertheless, patients should be followed up for 24 months to assess cure. Follow-up is based on parasitologic diagnosis and the analysis of CSF parameters.
Gambiense HAT
The disease has a chronic course with an evolution of several months to years from infection to first stage, to second stage, and finally death as a result of complications of the disease (infections, wasting situation, and cardiac or neurologic problems).[31]Checchi F, Filipe JA, Haydon DT, et al. Estimates of the duration of the early and late stage of gambiense sleeping sickness. BMC Infect Dis. 2008 Feb 8;8:16.
https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-8-16
http://www.ncbi.nlm.nih.gov/pubmed/18261232?tool=bestpractice.com
Treatment in first-stage disease with pentamidine has good results in terms of safety and efficacy, with low lethality (<0.5%) and high cure rate (around 95%).[135]Doua F, Miezan TW, Sanon Singaro JR, et al. The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense trypanosomiasis. Am J Trop Med Hyg. 1996 Dec;55(6):586-8.
http://www.ncbi.nlm.nih.gov/pubmed/9025682?tool=bestpractice.com
[136]Balasegaram M, Harris S, Checchi F, et al. Treatment outcomes and risk factors for relapse in patients with early-stage human African trypanosomiasis (HAT) in the Republic of the Congo. Bull World Health Organ. 2006 Oct;84(10):777-82.
http://www.ncbi.nlm.nih.gov/pubmed/17128357?tool=bestpractice.com
Fexinidazole presents equivalent efficacy to pentamidine in first-stage disease.[132]Kande Betu Ku Mesu V, Mutombo Kalonji W, Bardonneau C, et al. Oral fexinidazole for stage 1 or early stage 2 African Trypanosoma brucei gambiense trypanosomiasis: a prospective, multicentre, open-label, cohort study. Lancet Glob Health. 2021 Jul;9(7):e999-1008.
https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00208-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34143998?tool=bestpractice.com
Treatment in second-stage disease shows variable efficacy depending on the area and drugs used (70% to 95% cure rate) with considerable lethality depending on the drug used (0.15% to 10%). Eflornithine treatment has a mortality of 0.7% to 2% and an efficacy of around 90%, but in some areas (Kasai province in Democratic Republic of the Congo [DRC]) this efficacy is decreasing (80%).[137]Chappuis F, Udayraj N, Stietenroth K, et al. Eflornithine is safer than melarsoprol for the treatment of second-stage Trypanosoma brucei gambiense human African trypanosomiasis. Clin Infect Dis. 2005 Sep 1;41(5):748-51.
http://www.ncbi.nlm.nih.gov/pubmed/16080099?tool=bestpractice.com
The combination of nifurtimox plus eflornithine has shown a lower mortality (0.15% to 0.5%) and a cure rate of 95% to 98%.[32]World Health Organization. Guidelines for the treatment of human African trypanosomiasis. Jun 2024 [internet publication].
https://www.who.int/publications/i/item/9789240096035
[157]Alirol E, Schrumpf D, Amici Heradi J, et al. Nifurtimox-eflornithine combination therapy for second-stage Gambiense human African trypanosomiasis: Médecins sans Frontières experience in the Democratic Republic of the Congo. Clin Infect Dis. 2013 Jan;56(2):195-203.
http://www.ncbi.nlm.nih.gov/pubmed/23074318?tool=bestpractice.com
[158]Franco JR, Simarro PP, Diarra A, et al. Monitoring the use of nifurtimox-eflornithine combination therapy (NECT) in the treatment of second stage gambiense human African trypanosomiasis. Res Rep Trop Med. 2012 Aug 23;3:93-101.
https://www.dovepress.com/article/download/10808
http://www.ncbi.nlm.nih.gov/pubmed/30100776?tool=bestpractice.com
Fexinidazole presents equivalent efficacy to nifurtimox plus eflornithine in nonsevere second-stage disease (<100 white blood cells [WBC]/microliter in CSF), and inferior efficacy to nifurtimox plus eflornithine in severe second-stage disease (≥100 WBC/microliter in CSF). The mortality rate is around 1.5%.[133]Mesu VKBK, Kalonji WM, Bardonneau C, et al. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial. Lancet. 2018 Jan 13;391(10116):144-54.
http://www.ncbi.nlm.nih.gov/pubmed/29113731?tool=bestpractice.com
[134]Lutje V, Probyn K, Seixas J, et al. Chemotherapy for second-stage human African trypanosomiasis: drugs in use. Cochrane Database Syst Rev. 2021 Dec 9;(12):CD015374.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015374/full
http://www.ncbi.nlm.nih.gov/pubmed/34882307?tool=bestpractice.com
Melarsoprol shows a high mortality (3% to 10%) with variable efficacy. The level of treatment failure increased after the year 2000, reaching 59% in some areas of DRC.[138]Schmid C, Richer M, Bilenge CM, et al. Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (Impamel II). J Infect Dis. 2005 Jun 1;191(11):1922-31.
http://www.ncbi.nlm.nih.gov/pubmed/15871127?tool=bestpractice.com
[139]Kuepfer I, Schmid C, Allan M, et al. Safety and efficacy of the 10-day melarsoprol schedule for the treatment of second stage Rhodesiense sleeping sickness. PLoS Negl Trop Dis. 2012 Aug;6(8):e1695.
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001695
http://www.ncbi.nlm.nih.gov/pubmed/22970329?tool=bestpractice.com
Rhodesiense HAT
The disease has an acute course with an evolution of several weeks from infection to first stage to second-stage disease, and finally death as a result of complications of the disease (cardiac or neurologic problems, infections).[159]Fèvre EM, Coleman PG, Welburn SC, et al. Reanalyzing the 1900-1920 sleeping sickness epidemic in Uganda. Emerg Infect Dis. 2004 Apr;10(4):567-73.
https://wwwnc.cdc.gov/eid/article/10/4/02-0626_article
http://www.ncbi.nlm.nih.gov/pubmed/15200843?tool=bestpractice.com
Treatment in the first stage with suramin has good results in terms of safety and efficacy, with low lethality (<0.5%) and high cure rate (around 95%).[160]Fairlamb AH. Chemotherapy of human African trypanosomiasis: current and future prospects. Trends Parasitol. 2003 Nov;19(11):488-94.
http://www.ncbi.nlm.nih.gov/pubmed/14580959?tool=bestpractice.com
Treatment in the second stage with melarsoprol shows an adequate efficacy (90% to 97% cure rate) but with considerable lethality (5% to 10%).[140]Pepin J, Milord F. The treatment of human African trypanosomiasis. Adv Parasitol. 1994;33:1-47.
http://www.ncbi.nlm.nih.gov/pubmed/8122565?tool=bestpractice.com
Treatment outcome assessment is limited to patients in whom symptoms reappear.