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

Abstract

Background The World Health Organization recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. The efficacy of quinine plus clindamycin was compared with that of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in children below 5 years of age. Methods An open-label, phase 3, randomized trial was conducted in western Kenya. Children aged 6–59 months with uncomplicated falciparum malaria were randomly assigned (1:1) via a computer-generated randomization list to receive 3 days of twice a day treatment with either oral quinine (20 mg/kg/day) plus clindamycin (20 mg/kg/day) or artemether-lumefantrine (artemether 20 mg, lumefantrine 120 mg) as one (for those weighing 5–14 kg) or two (for those weighing 15–24 kg) tablets per dose. The primary outcome was a PCR-corrected rate of adequate clinical and parasitological response (ACPR) on day 28 in the per-protocol population. Results Of the 384 children enrolled, 182/192 (94.8%) receiving quinine plus clindamycin and 171/192 (89.1%) receiving artemether-lumefantrine completed the study. The PCR-corrected ACPR rate was 44.0% (80 children) in the quinine plus clindamycin group and 97.1% (166 children) in the artemether-lumefantrine group (treatment difference − 53.1%, 95% CI − 43.5% to − 62.7%). At 72 h after starting treatment, 50.3% (94 children) in the quinine plus clindamycin group were still parasitaemic compared with 0.5% (1 child) in the artemether-lumefantrine group. Three cases of severe malaria were recorded as serious adverse events in the quinine plus clindamycin group. Conclusions The study found no evidence to support the use of a 3-day low dose course of quinine plus clindamycin in the treatment of uncomplicated falciparum malaria in children under 5 years of age in Kenya, where artemether-lumefantrine is still effective. Trial Registration: This trial is registered with the Pan-African Clinical Trials Registry, PACTR20129000419241.

Practical Applications of Supramolecular Macrocyclic Hosts in the Field of Herbal Medicines

“…Furthermore, scanning electron microscopy (SEM), [55] transmission electron microscope (TEM), [49] and dynamic light scattering (DLS) [59] have been frequently employed to perform determination of molecular sizes and morphologies of the tested samples. Consoli and Cuzzocrea, et al have developed a calix [4]arene-curcumin supramolecular assembly (Calix-Cur) as a promising nanocarrier for delivering curcumin to anterior ocular tissues. The size and morphology of the Calix-Cur were characterized by DLS and TEM measurements.…”

“…This versatility allows for the development of diverse drug delivery strategies. [140] In 2017, Consoli and Cuzzocrea et al introduced an ocular drug delivery system composed of a calix [4]arene nano-assembly (Figure 7). This system exhibited a significant improvement in the solubility, stability, and anti-inflammatory effects of curcumin compared to free curcumin, as demonstrated by both in vitro and in vivo experiments.…”

“…Our research group has developed a novel, straightforward, and label-free fluorescence IDA strategy for screening potential inhibitors of flavin monooxygenase 3 (FMO3) from Xuefu Zhuyu decoction (Figure 3). This approach utilizes a host-guest system consisting of p-sulfonatocalix [4]arene (SC4A) and oxazine 1 as the reporter pair. Through this strategy, we successfully identified naringin, paeoniflorin, βecdysterone, 18β-glycyrrhizic acid, amygdalin, albiflorin, and saikosaponin A as active compounds.…”

Potential of nanoformulations in malaria treatment

“…Combined antimalarial treatments that do not present artemisinin (ART) are recommended by the WHO when unavailable or suitable for treatment ( Who, 2015 ). An open randomized phase III clinical study compared the efficacy of quinine/clindamycin with artemether/lumefantrine in treating uncomplicated malaria in children below 5 years of age and did not find evidence for the use of quinine/clindamycin when artemether/lumefantrine is still effective ( Obonyo et al, 2022 ). A single monthly prophylactic antimalarial drug composed of a combination of naphthoquinone-azithromycin (NQAZ) was used in a randomized, placebo-controlled, double-blind study to evaluate its protective effect against Plasmodium infection.…”

Need for optimized dosages in the design of comparative clinical trials of anti-malarial drugs

“…A recent clinical trial conducted on Kenyan children by Obonyo et al compared malaria treatment with quinine (10 mg/kg quinine sulphate: bd) given with clindamycin (10 mg/kg: bd) for six doses with artemether–lumefantrine (administered in weight adjusted rounded dosages) [ 1 ]. According to the authors, only 44% (n = 80) of children given quinine + clindamycin had an adequate clinical and parasitological response compared with 97% (n = 166) in the artemether-lumefantrine treatment group.…”