TY - JOUR

T1 - Second stage human African Trypanosomiasis with Trypanosoma brucei rhodesiense treated with fexinidazole

AU - Helleberg, Barbara Brask

AU - Gudmundsson, Katrine Snorradottir Steen

AU - Kurtzhals, Jørgen Anders Lindholm

AU - Helleberg, Marie

PY - 2023

Y1 - 2023

N2 - A man aged 60 years was admitted to Copenhagen University Hospital, with high grade fever (41°C), headache, and joint pain 7 days after returning from a two-week hunting safari in Zambia in Munyamadzi Game Ranch and Kazumba Game Ranch (Nyimba district), Luangwa Valley. He had contracted several tsetse fly bites. Physical examination showed a chancre on the right leg (figure 1A). Blood biochemistry revealed severe lymphopenia (0·2 × 109/L), low platelets (32 × 109/L), and elevated D-dimer (39 FEU/L). A loop-mediated isothermal amplification test for malaria was negative. A Giemsa-stained blood smear showed Trypanosoma spp (figure 1B) and metagenome sequencing determined the species as Trypanosoma brucei rhodesiense. Treatment with intravenous pentamidine was initiated and showed clinical improvement. After 5 days of treatment, platelets had increased to greater than 40 × 109/L and a lumbar puncture was performed. The cerebrospinal fluid cell count was 70 × 106/L, indicating second stage disease. Microscopy, metagenome sequencing, and specific TaqMan (Thermo Fisher Scientific, US) PCR, targeting a 103bp sequence of the 18S gene of T. brucei, were negative. The available treatment for second stage Tb rhodesiense is melarsoprol, which is toxic with a high frequency of severe, and sometimes fatal, adverse drug reactions (3–10% treatment-related fatality rate). Considering the potential risks associated with melarsoprol treatment and based on informal results of a clinical trial (NCT03974178), we decided to pursue off-label treatment with fexinidazole. The drug was procured through WHO, and the patient received 10 days of oral treatment. The patient received 1800 mg once a day for 4 days, followed by 1200 mg once a day for 6 days. He experienced no side-effects and showed no sign of relapse during a 6-month follow-up. The patient is still being regularly monitored.

AB - A man aged 60 years was admitted to Copenhagen University Hospital, with high grade fever (41°C), headache, and joint pain 7 days after returning from a two-week hunting safari in Zambia in Munyamadzi Game Ranch and Kazumba Game Ranch (Nyimba district), Luangwa Valley. He had contracted several tsetse fly bites. Physical examination showed a chancre on the right leg (figure 1A). Blood biochemistry revealed severe lymphopenia (0·2 × 109/L), low platelets (32 × 109/L), and elevated D-dimer (39 FEU/L). A loop-mediated isothermal amplification test for malaria was negative. A Giemsa-stained blood smear showed Trypanosoma spp (figure 1B) and metagenome sequencing determined the species as Trypanosoma brucei rhodesiense. Treatment with intravenous pentamidine was initiated and showed clinical improvement. After 5 days of treatment, platelets had increased to greater than 40 × 109/L and a lumbar puncture was performed. The cerebrospinal fluid cell count was 70 × 106/L, indicating second stage disease. Microscopy, metagenome sequencing, and specific TaqMan (Thermo Fisher Scientific, US) PCR, targeting a 103bp sequence of the 18S gene of T. brucei, were negative. The available treatment for second stage Tb rhodesiense is melarsoprol, which is toxic with a high frequency of severe, and sometimes fatal, adverse drug reactions (3–10% treatment-related fatality rate). Considering the potential risks associated with melarsoprol treatment and based on informal results of a clinical trial (NCT03974178), we decided to pursue off-label treatment with fexinidazole. The drug was procured through WHO, and the patient received 10 days of oral treatment. The patient received 1800 mg once a day for 4 days, followed by 1200 mg once a day for 6 days. He experienced no side-effects and showed no sign of relapse during a 6-month follow-up. The patient is still being regularly monitored.

KW - Animals

KW - Humans

KW - Trypanosomiasis, African/drug therapy

KW - Trypanosoma brucei rhodesiense

KW - Nitroimidazoles/therapeutic use

KW - Trypanocidal Agents/therapeutic use

U2 - 10.1016/S1473-3099(23)00358-4

DO - 10.1016/S1473-3099(23)00358-4

M3 - Journal article

C2 - 37890908

VL - 23

JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

SN - 1473-3099

IS - 11

M1 - e505

ER -