Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial.
BACKGROUND
Morbidity control of schistosomiasis relies on a single drug, praziquantel. The antimalarial drug mefloquine possesses interesting antischistosomal properties, yet no clinical studies have been performed.


METHODS
We conducted a randomized, exploratory open-label trial to assess the efficacy and safety of mefloquine (25 mg/kg), artesunate (3 doses of 4 mg/kg), mefloquine-artesunate (3 doses of 100 mg artesunate plus 250 mg mefloquine), and praziquantel (40 mg/kg) against Schistosoma haematobium. The effects on Schistosoma mansoni, malaria parasitemia, soil-transmitted helminths, and intestinal protozoa were also determined.


RESULTS
A total of 83 S. haematobium-infected schoolchildren were included in the study. Cure rates of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against S. haematobium at day 26 after treatment were 21%, 25%, 61%, and 88%, respectively. Both mefloquine-artesunate and praziquantel resulted in egg reduction rates >95%. Significantly lower egg reduction rates were seen in the artesunate (85%) and mefloquine groups (74%). In children coinfected with S. mansoni, praziquantel and mefloquine-artesunate, but not mefloquine and artesunate alone, resulted in high cure rates and egg reduction rates. Mefloquine, artesunate, and mefloquine-artesunate completely cured infections due to Plasmodium falciparum. No effects were found against soil-transmitted helminths and intestinal protozoa. Abdominal pain was the most frequent adverse event, with a higher incidence among children treated with mefloquine (89%), mefloquine-artesunate (83%), and artesunate (60%) than among children treated with praziquantel (46%).


CONCLUSIONS
The high efficacy of mefloquine-artesunate against S. haematobium warrants further investigation. Individuals coinfected with Plasmodium and Schistosoma who were treated with a mefloquine-artesunate combination against malaria might have a dual benefit: clearance of malaria parasitemia and reduction of schistosomiasis-related morbidity.


BACKGROUND
Current Controlled Trials identifier: ISRCTN06498763.
Keiser
Jennifer
J
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland. jennifer.keiser@unibas.ch
N'Guessan
Nicaise A
NA
Adoubryn
Koffi D
KD
Silué
Kigbafori D
KD
Vounatsou
Penelope
P
Hatz
Christoph
C
Utzinger
Jürg
J
N'Goran
Eliézer K
EK
D015746:Abdominal Pain / Q000139:chemically induced; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000009:adverse effects; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects; D000077332:Artesunate; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015994:Incidence; D016778:Malaria, Falciparum / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage* / Q000009:adverse effects; D010270:Parasite Egg Count; D010963:Plasmodium falciparum / Q000187:drug effects; D011223:Praziquantel / Q000008:administration & dosage* / Q000009:adverse effects; D012548:Schistosoma haematobium / Q000187:drug effects / Q000302:isolation & purification; D012553:Schistosomiasis haematobia / Q000188:drug therapy*; D016896:Treatment Outcome
D000871:Anthelmintics; D037621:Artemisinins; D000077332:Artesunate; D011223:Praziquantel; D015767:Mefloquine