Should we abandon quinine plus antibiotic for treating uncomplicated falciparum malaria? A systematic review and meta-analysis of randomized controlled trials

Abstract

In this study, we compared the efficacies and adverse effects of quinine plus antibiotics and other anti-malaria drugs on treating uncomplicated falciparum malaria. By systematically searching the major databases PubMed, Embase, and the Cochrane Library, 14 randomized controlled trials (RCTs) including 1996 cases were identified. Then, we performed a systematic review and cumulative meta-analysis on these data. The primary outcome of these treatments was parasite failure at day 28. There was no significant difference between quinine plus antibiotic therapy (QACT) and artemisinin-based therapies (odds ratio (OR) 0.69, 95 % confidence interval (CI) 0.28 to 1.71) or non-artemisinin-based therapies except quinine monotherapy and chloroquine monotherapy (OR 0.56, 95 % CI 0.18 to 1.74). The secondary outcome was the adverse effects within 28 days, including nausea, dizziness, vomiting, diarrhea, abdominal pain, headache, and tinnitus. QACT significantly increased the risk of tinnitus compared with artemisinin-based therapies (OR 111.65, 95 % CI 12.63 to 986.87) and non-artemisinin-based therapies (OR 48.16, 95 % CI 16.23 to 142.92). Vomiting was more frequently reported in QACT compared with non-artemisinin-based therapies (OR 2.02, 95 % CI 1.14 to 3.56). This meta-analysis suggests that almost all regimens have equivalent treatment effect at the 28th day. However, the patients with QACT had a higher chance to suffer from vomiting and tinnitus. Therefore, QACT does not have significant advantage on treating uncomplicated falciparum malaria.

Efficacy of Quinine Plus Clindamycin Versus Artemether-Lumefantrine For The Treatment of Uncomplicated Plasmodium Falciparum Malaria In Kenyan Children (CLINDAQUINE): An Open-Label Randomised Trial

“…However, in the treatment of uncomplicated falciparum malaria in children, we found PCRadjusted ACPR rates of 44% with quinine plus clindamycin and 97% with artemether-lumefantrine on day 28 after treatment. This is inconsistent with the ndings of the QUINACT trial or the review by Song et al [14,17]. In the QUINACT trial, quinine plus clindamycin had similar e cacy as artesunate plus amodiaquine and artemether-lumefantrine as rescue treatment for recurrent falciparum malaria in children [17].…”

“…In the QUINACT trial, quinine plus clindamycin had similar e cacy as artesunate plus amodiaquine and artemether-lumefantrine as rescue treatment for recurrent falciparum malaria in children [17]. A review found no signi cant difference in e cacy between quinine plus antibiotics compared with that of ACTs [14].…”

“…Children treated using quinine plus clindamycin were more likely to develop severe adverse events associated with worsening of the malaria infection. The meta-analysis by Song et al found that treatment with quinine plus antibiotics was associated with an increased risk of tinnitus and vomiting [14].…”

“…One systematic review of seven randomized trials found inconclusive evidence on the e cacy of quinine plus clindamycin compared with other antimalarials (alone or in combination) in the treatment of uncomplicated falciparum malaria [13]. Another systematic review of 14 randomized trials found no difference in e cacy between quinine plus antibiotics compared with artemisinin-based and nonartemisinin-based combinations in the treatment of uncomplicated falciparum malaria [14]. There is no published study comparing the e cacy of quinine plus clindamycin with the recommended artemisininbased combinations in the primary treatment of uncomplicated falciparum malaria.…”

Efficacy of 3-day low dose quinine plus clindamycin versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children (CLINDAQUINE): an open-label randomized trial

“…One systematic review of seven randomized trials found inconclusive evidence on the efficacy of quinine plus clindamycin compared with other anti-malarials (alone or in combination) in the treatment of uncomplicated falciparum malaria [ 16 ]. Another systematic review of 14 randomized trials found no difference in efficacy between quinine plus antibiotics compared with artemisinin-based and non-artemisinin-based combinations in the treatment of uncomplicated falciparum malaria [ 17 ]. There is no published study comparing the efficacy of quinine plus clindamycin with the recommended artemisinin-based combinations in the primary treatment of uncomplicated falciparum malaria.…”