Effectiveness of antimalarial drug combinations in treating concomitant urogenital schistosomiasis in malaria patients in Lambaréné, Gabon: A non-randomised event-monitoring study

TY - JOUR

T1 - Effectiveness of antimalarial drug combinations in treating concomitant urogenital schistosomiasis in malaria patients in Lambaréné, Gabon: A non-randomised event-monitoring study

AU - Zoleko-Manego, Rella

AU - Okwu, Dearie G

AU - Handrich, Christian

AU - Dimessa-Mbadinga, Lia B

AU - Akinosho, Malick A

AU - Ndzebe-Ndoumba, Wilfrid F

AU - Davi, Saskia D

AU - Stelzl, Daniel

AU - Veletzky, Luzia

AU - Kreidenweiss, Andrea

AU - Nordmann, Tamara

AU - Adegnika, Ayola A

AU - Lell, Bertrand

AU - Kremsner, Peter G

AU - Ramharter, Michael

AU - Mombo-Ngoma, Ghyslain

N1 - Copyright: © 2022 Zoleko-Manego et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/10

Y1 - 2022/10

N2 - BACKGROUND: Urogenital schistosomiasis is prevalent in many malaria endemic regions of sub-Saharan Africa and can lead to long-term health consequences if untreated. Antimalarial drugs used to treat uncomplicated malaria have shown to exert some activity against Schistosoma haematobium. Here, we explore the efficacy on concomitant urogenital schistosomiasis of first-line recommended artemisinin-based combination therapies (ACTs) and investigational second-generation ACTs when administered for the treatment of uncomplicated malaria in Gabon.METHODS: Microscopic determination of urogenital schistosomiasis was performed from urine samples collected from patients with confirmed uncomplicated malaria. Egg excretion reduction rate and cure rate were determined at 4-weeks and 6-weeks post-treatment with either artesunate-pyronaridine, artemether-lumefantrine, artesunate-amodiaquine or artefenomel-ferroquine.RESULTS: Fifty-two (16%) out of 322 malaria patients were co-infected with urogenital schistosomiasis and were treated with antimalarial drug combinations. Schistosoma haematobium egg excretion rates showed a median reduction of 100% (interquartile range (IQR), 17% to 100%) and 65% (IQR, -133% to 100%) at 4-weeks and 6-weeks post-treatment, respectively, in the artesunate-pyronaridine group (n = 20) compared to 35% (IQR, -250% to 70%) and 65% (IQR, -65% to 79%) in the artemether-lumefantrine group (n = 18). Artesunate-amodiaquine (n = 2) and artefenomel-ferroquine combination (n = 3) were not able to reduce the rate of eggs excreted in this limited number of patients. In addition, cure rates were 56% and 37% at 4- and 6-weeks post-treatment, respectively, with artesunate-pyronaridine and no cases of cure were observed for the other antimalarial combinations.CONCLUSIONS: Antimalarial treatments with artesunate-pyronaridine and artemether-lumefantrine reduced the excretion of S. haematobium eggs, comforting the hypothesis that antimalarial drugs could play a role in the control of schistosomiasis.TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov, under the Identifier NCT04264130.

AB - BACKGROUND: Urogenital schistosomiasis is prevalent in many malaria endemic regions of sub-Saharan Africa and can lead to long-term health consequences if untreated. Antimalarial drugs used to treat uncomplicated malaria have shown to exert some activity against Schistosoma haematobium. Here, we explore the efficacy on concomitant urogenital schistosomiasis of first-line recommended artemisinin-based combination therapies (ACTs) and investigational second-generation ACTs when administered for the treatment of uncomplicated malaria in Gabon.METHODS: Microscopic determination of urogenital schistosomiasis was performed from urine samples collected from patients with confirmed uncomplicated malaria. Egg excretion reduction rate and cure rate were determined at 4-weeks and 6-weeks post-treatment with either artesunate-pyronaridine, artemether-lumefantrine, artesunate-amodiaquine or artefenomel-ferroquine.RESULTS: Fifty-two (16%) out of 322 malaria patients were co-infected with urogenital schistosomiasis and were treated with antimalarial drug combinations. Schistosoma haematobium egg excretion rates showed a median reduction of 100% (interquartile range (IQR), 17% to 100%) and 65% (IQR, -133% to 100%) at 4-weeks and 6-weeks post-treatment, respectively, in the artesunate-pyronaridine group (n = 20) compared to 35% (IQR, -250% to 70%) and 65% (IQR, -65% to 79%) in the artemether-lumefantrine group (n = 18). Artesunate-amodiaquine (n = 2) and artefenomel-ferroquine combination (n = 3) were not able to reduce the rate of eggs excreted in this limited number of patients. In addition, cure rates were 56% and 37% at 4- and 6-weeks post-treatment, respectively, with artesunate-pyronaridine and no cases of cure were observed for the other antimalarial combinations.CONCLUSIONS: Antimalarial treatments with artesunate-pyronaridine and artemether-lumefantrine reduced the excretion of S. haematobium eggs, comforting the hypothesis that antimalarial drugs could play a role in the control of schistosomiasis.TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov, under the Identifier NCT04264130.

KW - Humans

KW - Amodiaquine/therapeutic use

KW - Antimalarials/therapeutic use

KW - Artemether

KW - Artemether, Lumefantrine Drug Combination/therapeutic use

KW - Artesunate/therapeutic use

KW - Drug Combinations

KW - Ethanolamines/therapeutic use

KW - Gabon/epidemiology

KW - Malaria/drug therapy

KW - Malaria, Falciparum/complications

KW - Schistosomiasis haematobia/complications

U2 - 10.1371/journal.pntd.0010899

DO - 10.1371/journal.pntd.0010899

M3 - SCORING: Journal article

C2 - 36315579

VL - 16

JO - PLOS NEGLECT TROP D

JF - PLOS NEGLECT TROP D

SN - 1935-2735

IS - 10

M1 - e0010899

ER -