Effects of Oral Fexinidazole in Patients With Stage II Human African Trypanosomiasis

Investigators conducted a study that compared the safety and effectiveness of oral fexinidazole with nifurtimox-eflornithine combination therapy for the treatment of stage II gambiense human African trypanosomiasis.

Although oral fexinidazole was found to be both a convenient and cost-effective treatment for patients with stage II gambiense human African trypanosomiasis (g-HAT), it may be associated with an increased mortality and relapse rate compared with other g-HAT treatments. These findings were published in the Cochrane Database of Systematic Reviews.

Investigators conducted a review of randomized controlled trials that enrolled adults and children with stage II g-HAT. A diagnosis of stage II g-hat was defined as having a leukocyte count greater than 5 cells/mcL with or without trypanosomes on cerebrospinal fluid (CSF) analysis, as well as evidence of trypanosomal infection. The investigators sought to compare the effects of oral fexinidazole with nifurtimox-eflornithine combination therapy (NECT) for the treatment of stage II g-HAT. Studies of adults and children who relapsed after g-HAT treatment were also included in the review.

The primary outcomes were all-cause mortality and g-HAT relapse up to 24 months. The secondary outcome was treatment failure up to 24 months.

There was 1 randomized controlled trial (RCT) that met the inclusion criteria.  The RCT comprised 394 patients aged 15 years and older with stage II g-HAT. Patients were randomly assigned in a 2:1 fashion to receive either oral fexinidazole or NECT for 10 days. The trial was conducted at 10 sites in the Democratic Republic of the Congo and the Central African Republic.

Among a total of 394 patients included in the trial, 264 received oral fexinidazole and 130 received NECT. During treatment, there were 2 deaths among patients in the oral fexinidazole group vs none among those in the NECT group (risk difference [RD], 0.01; 95% CI, -0.01 to 0.02). At 24 months’ follow-up, there were 9 and 2 deaths among patients in the oral fexinidazole and NECT groups, respectively (RR, 2.22; 95% CI, 0.49-10.11). Of note, none of the 11 deaths were considered related to treatment; however, causes of death were not reported.

After a 24-month follow-up, oral fexinidazole was associated with an increased risk for g-HAT relapse compared with NECT, with 14 relapses among patients in the fexinidazole vs none in the NECT group (RD, 0.05; 95% CI, 0.02-0.08).

Of note, treatment failure at 24 months occurred among 27 and 3 patients in the oral  fexinidazole and NECT treatment groups, respectively (RR, 4.43; 95% CI, 1.37-14.34).

The investigators noted that adverse events at 24-months’ follow-up were common among included patients, with 247 and 121 adverse events reported among those in the oral fexinidazole and NECT groups, respectively.

This review was limited by the fact that only 1 study met the inclusion criteria, In addition, the overall certainty of the evidence ranged from very low to moderate.

According to the investigators, “fexinidazole has the advantages expected of an oral treatment [for patients with stage II g-HAT], such as removal of the need for infusions and systematic hospitalization, as well as [decreased] costs.”


Lutje V, Probyn K, Seixas J, Bergman H, Villanueva G. Chemotherapy for second-stage human African trypanosomiasis: drugs in use. Cochrane Database Syst Rev. Published online December 9, 2021. doi:10.1002/14651858.CD015374