Clindamycin plus quinine for treating uncomplicated falciparum malaria: a systematic review and meta-analysis

BACKGROUND: Artemisinin-based combinations are recommended for treatment of uncomplicated falciparum malaria, but are costly and in limited supply. Clindamycin plus quinine is an alternative non-artemisinin-based combination recommended by World Health Organization. The efficacy and safety of clindamycin plus quinine is not known. This systematic review aims to assess the efficacy of clindamycin plus quinine versus other anti-malarial drugs in the treatment of uncomplicated falciparum malaria. METHODS: All randomized controlled trials comparing clindamycin plus quinine with other anti-malarial drugs in treating uncomplicated malaria were included in this systematic review. Databases searched included: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. Two authors independently assessed study eligibility, extracted data and assessed methodological quality. The primary outcome measure was treatment failure by day 28. Dichotomous data was compared using risk ratio (RR), in a fixed effects model. RESULTS: Seven trials with 929 participants were included. Clindamycin plus quinine significantly reduced the risk of day 28 treatment failure compared with quinine (RR 0.14 [95% CI 0.07 to 0.29]), quinine plus sulphadoxine-pyrimethamine (RR 0.17 [95% CI 0.06 to 0.44]), amodiaquine (RR 0.11 [95% CI 0.04 to 0.27]), or chloroquine (RR 0.11 [95% CI 0.04 to 0.29]), but had similar efficacy compared with quinine plus tetracycline (RR 0.33 [95% CI 0.01 to 8.04]), quinine plus doxycycline (RR 1.00 [95% CI 0.21 to 4.66]), artesunate plus clindamycin (RR 0.57 [95% CI 0.26 to 1.24]), or chloroquine plus clindamycin (RR 0.38 [95% CI 0.13 to 1.10]). Adverse events were similar across treatment groups but were poorly reported. CONCLUSION: The evidence on the efficacy of clindamycin plus quinine as an alternative treatment for uncomplicated malaria is inconclusive. Adequately powered trials are urgently required to compare this combination with artemisinin-based combinations.