The risk factors associated with gametocytaemia at presentation and after treatment with different antimalarial drug regimens were evaluated in 767 children enrolled prospectively in 5 antimalarial drug trials between July 1996 and December 2002 in a hyperendemic area of southwestern Nigeria. The children were assigned to one of 6 treatment groups: chloroquine (CQ) only; pyrimethamine-sulfadoxine (PS) only; amodiaquine (AQ) only; CQ combined with chlorpheniramine (CQCP); or PS combined with CQ (CQPS) or AQ (AQPS). At enrolment, 115 (15%) of 767 children were gametocyte carriers. During follow-up, 15.6% of all patients (i.e. 120 patients) developed patent gametocytaemia, which in 85% (102 patients) had developed by day 7 following treatment. In a multiple regression model, 4 factors were found to be independent risk factors for the presence of gametocytaemia at enrolment: male gender (adjusted odds ratio [AOR] = 0.55, 95% confidence interval [CI] 0.36-0.83, P=0.005), absence of fever (AOR = 1.61, 95% CI 1.05-2.5, P=0.03), duration of illness >3 days (AOR=1.57, 95% CI 1.0-2.4, P=0.047), and asexual parasite densities less than 5000/microl (AOR=0.42, 95% CI 0.24-0.73, P=0.002). The presence of patent gametocytaemia at enrolment (AOR=0.04, 95% CI 0.02-0.07, P<0.001) and recrudescence of asexual parasites within 14 days were associated with the presence of gametocytaemia 7 or 14 days after enrolment (AOR=0.5, 95% CI 0.3-0.8, P=0.007). Delay in the time taken to clear the initial parasitaemia (>2 days) was associated with increased risk of subsequent gametocyte carriage. These findings may have implications for malaria control efforts in sub-Saharan Africa where control of the disease depends almost entirely on chemotherapy.

The activities of amodiaquine, artesunate, and artesunate-amodiaquine against asexual-and sexual-stage parasites were evaluated in 360 Nigerian children with uncomplicated Plasmodium falciparum malaria randomized to the standard dose regimens of the three drugs/combination. Clinical recovery from illness occurred in all children. There were no significant differences in fever clearance times. Patients treated with artesunate or artesunate-amodiaquine had significantly shorter parasite clearance times (1.4 ؎ 0.5 days or 1.4 ؎ 0.6 days versus 3.2 ؎ 2.3 days, P ‫؍‬ 0.0001) and lower gametocyte carriage rates (3.3 or 1.7% versus 11.7%, P ‫؍‬ 0.001) than those treated with amodiaquine alone. Gametocytemia was detected in 62 patients (11.7% before treatment and 5.6% after treatment). The pretreatment gametocyte sex ratio, which was female biased, increased significantly during the course of treatment with amodiaquine but not with artesunate and artesunateamodiaquine. These results suggest that artesunate and artesunate-amodiaquine reduce gametocyte carriage and may reduce transmissibility in P. falciparum malaria by accelerating asexual clearance and influencing gametocyte sex ratio.

This review aims at providing synthetic information with scientific evidence on the trends in the malaria events from 1960 to 2011, with the hope that it will help policy makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in both Sub-Sahara Africa and in the People’s Republic of China by highlighting the achievements, progress and challenges in research on moving malaria from epidemic status towards elimination. Our findings showed that since 1960, malaria control programmes in most countries have been disjointed and not harmonized. Interestingly, during the last decade, the causal factors of the unprecedented and substantial decline in malaria morbidity and mortality rates in most vulnerable groups in these endemic areas are multifaceted, including not only the spread of malaria and its related effects but also political and financial willingness, commitment and funding by governments and international donors. The benefits of scaling up the impact of malaria coverage interventions, improvement of health system approaches and sustained commitment of stakeholders are highlighted, although considerable efforts are still necessary in Sub-Sahara Africa. Furthermore, novel integrated control strategies aiming at moving malaria from epidemic status to control towards elimination, require solid research priorities both for sustainability of the most efficient existing tools and intervention coverage, and in gaining more insights in the understanding of the epidemiology, pathogenesis, vector dynamics, and socioeconomic aspects of the disease. In conclusion, political commitment and financial investment of stakeholders in sustaining the scaling up impact of malaria control interventions, networking between African and Chinese scientists, and their Western partners are urgently needed in upholding the recent gains, and in translating lessons learnt from the Chinese malaria control achievements and successes into practical interventions in malaria endemic countries in Africa and elsewhere.

The treatment efficacy and effects of artemether-lumefantrine (AL) and amodiaquine-sulfalene-pyrimethamine (ASP) on gametocyte carriage were evaluated in 181 children < or = 10 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive either drug combination. All children recovered clinically. Fever clearance times were similar. The rate of P. falciparum reappearance (recrudescence or re-infection) between two and six weeks after the start of therapy was significantly higher in AL-treated children (P = 0.01). Parasite clearance was significantly faster in children treated with AL (mean +/- SD = 1.7 +/- 0.6 days, 95% confidence interval = 1.58 - 1.83, P = 0.0001) but the polymerase chain reaction-corrected cure rate (90 of 91 versus 84 of 90) and the rate of resolution of malaria-related anemia two weeks after treatment began (45 of 50 versus 33 of 46) were higher in children treated with ASP. Gametocyte carriage rates were similar. Both regimens were well tolerated. Artemether-lumefantrine clears parasitemia more rapidly than ASP but both combinations are effective in treatment of uncomplicated P. falciparum malaria in Nigerian children.

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Summarybackground Increasing drug resistance in Plasmodium falciparum has necessitated renewed search for cheap, effective alternatives to commonly available antimalarials, chloroquine and pyrimethaminesulphadoxine, for the treatment of malaria in Africa. Probenecid, an inhibitor of organic anion transporters and multiresistance-associated proteins, can chemosensitize P. falciparum to pyrimethamine and sulphadoxine in vitro, but the clinical significance is unclear. We assessed the safety, treatment efficacy, and effects on gametocyte carriage of adding probenecid to pyrimethaminesulphadoxine.methods We evaluated 151 children aged 12 years or younger who had uncomplicated P. falciparum malaria. Patients were randomly assigned pyrimethamine-sulphadoxine (25 mg/kg of the sulphadoxine component) or pyrimethamine-sulphadoxine as above plus probenecid 20-25 mg/kg of bodyweight in two divided doses daily for 3 days. The primary endpoints were parasitological cure rates on days 14 and 28.results Both regimens were well tolerated; no child was withdrawn because of drug intolerance. Fever (1.9 ± 1.1 vs. 2.4 ± 1.2 days, P ¼ 0.02) and parasite clearance (2.3 ± 0.9 vs. 2.7 ± 1.1 days, P ¼ 0.04) were significantly shorter, and the parasitological cure rate on day 14 (96.2% vs. 83.5%, P ¼ 0.02) but not day 28 (79.4% vs. 72.6%, P ¼ 0.4), was significantly higher in children treated with pyrimethamine-sulphadoxine-probenecid than in those treated with pyrimethamine-sulphadoxine. Gametocyte carriage was similar with both treatment regimens.conclusions The combination of pyrimethamine-sulphadoxine, and probenecid, at a relatively moderate dose, improved treatment efficacy but had no effect on gametocyte carriage. The pyrimethamine-sulphadoxine-probenecid combination merits further evaluation as a potential treatment for use in Nigeria.

Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS), df = 1, P = 0.02). Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.