Comparative activities of chloroquine mefloquine and sulphadoxine-pyrimethamine on in vivo and ex vivo male reproductive functions in mammalian models

Comparative reproductive activities of chloroquine, mefloquine and sulphadoxine-pyrimethamine were explored in albino Wistar rats and semen from West African Dwarf Buck [WADB] with a view to elucidating the mechanism of action of these drugs on malereproduction. Five adult male rats were administered 0.5 mL distilled water and served as the control. Five rats each were administered orally chloroquine [10 mg kg -1 b.w.], mefloquine [10 mg kg -1 b.w.] and sulphadoxine-pyrimethamine [5 mg kg -1 b.w.] orally, for four weeks. Each group had it's own recovery group. Sperm counts, motility and morphology were reduced in rats treated with these drugs in the order mefloquine [p<0.05]> chloroquine > sulphadoxine-pyrimethamine. There was an appreciable recovery in the motility of sperms in all recovery groups. Semen samples from WADB were extended separately with chloroquine, mefloquine and sulphadoxine-pyrimethamine. Extender 1 [first control] had no PENSTRIP [Penicillin and Streptomycin combination] while extender 2 [standard extender; second control] had PENSTRIP. Semen in extenders 3, 4 and 5 were treated with chloroquine, mefloquine and sulphadoxine-pyrimethamine, respectively. Spermatozoa progressive motility in these extenders examined under the microscope at 24 h for 5 days significantly reduced in mefloquine [p<0.01], slightly with chloroquine and unchanged with sulphadoxine-pyrimethamine. The pH of the extenders was significantly reduced in duration dependent manner in mefloquine while it remained unchanged with chloroquine and sulphadoxine-pyrimethamine. The results suggest the safety of sulphadoxine-pyrimethamine and chloroquine in preservation of semen ex vivo while the negative impact of mefloquine could reside within the testis or epididymis

Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial.

At a time when Fansimef, the fixed combination of mefloquine, sulfadoxine and pyrimethamine was considered for prophylaxis of falciparum malaria, a randomized double-blind study comparing the efficacy and tolerability of Fansimef with that of Lariam (mefloquine), Fansidar, chloroquine and placebo in malaria prophylaxis was performed in Thailand from July 1987 to January 1988. The study population of 602 adult males was recruited in Pak Tongchai District, some 360 km North-East of Bangkok, where multiresistant P. falciparum is endemic. All active treatments and placebo were given once weekly for 24 weeks with doses as follows: Fansimef: 125 mg mefloquine + 250 mg sulfadoxine + 12.5 mg pyrimethamine (1 half-strength tablet); Lariam: 125 mg mefloquine (1 half-strength tablet); Fansidar: 500 mg sulfadoxine + 25 mg pyrimethamine; chloroquine; 300 mg. A loading dose of 2 half-strength tablets was given in the Fansimef group in weeks 1 and 2 and in the Lariam group in weeks 1 to 4. The incidence of acute episodes of P. falciparum per 100 person months of prophylaxis was 0.17 each in the Fansimef and the Lariam groups, 1.18 in the Fansidar group, 0.69 in the chloroquine group and 0.64 in the placebo group (differences statistically not significant). Clinically adverse events were reported by 170 subjects (Fansimef 28, Lariam 29, Fansidar 41, choroquine 43, placebo 29; differences statistically not significant). The most frequent adverse events in all groups were headache, sleepiness, dizziness and weakness.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical trials of mefloquine with tetracycline.

A comparative trial of the combination of mefloquine or MSP with tetracycline was carried out in fifty-one adult Thai male patients with acute falciparum malaria. The patients were randomized to receive either the combination of tetracycline (250 mg qid for 7 days) with mefloquine 4 tablets (1,000 mg) or with MSP 4 tablets (one tablet contains 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine). Fifty patients had a complete 28-day follow-up period. Both regimens produced similar efficacy with no difference in adverse effects. In the mefloquine plus tetracycline group, the cure rate was 72% (18/25). One patient had an RIII response, the others showed initial response to the treatment with FCT and PCT of 40.7 +/- 27.4 and 76.2 +/- 34.2 hours (mean +/- SD) respectively. However, 6 patients developed recrudescence between days 17 and 29 (RI), 3 of these had vomiting. In the MSP plus tetracycline group, the cure rate was 76% (19/25). The means (+/- SD) of FCT and PCT were 44.7 +/- 38.0 and 80.6 +/- 25.0 hours, respectively. Six patients had recrudescence between days 17 and 31 (RI), 2 of these had vomiting. Although the addition of tetracycline improved the cure rate of mefloquine when compared with standard dose of mefloquine alone (3 tablets), these combinations seem to be useful in areas where alternative drugs are not available.

Oral lichenoid reactions during antimalarial prophylaxis with sulphadoxine-pyrimethamine combination.

The prevalence of clinically observed oral lichenoid reaction in 186 Malay army personnel using Fansidar for 9 weeks was found to be 4.8%. The prevalence was found to be 0.5% in 186 army personnel who had stopped using Fansidar for 2 months and 0% in 143 army personnel (control group) who had not used Fansidar for at least 4 months. The lesion showed a higher prevalence for the gingiva. There was no correlation between cigarette smoking and the occurrence of these lesions in each group.