In Vivo Efficacy of Artesunate/Sulphadoxine-Pyrimethamine versus Artesunate/Amodiaquine in the Treatment of Uncomplicated P. falciparium Malaria in Children around the Slope of Mount Cameroon: A Randomized Controlled Trial

Background: The development and spread of antimalarial drug resistant parasites contributes to the global impact of the disease. In vivo efficacy assessments of treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. Artemisinin-based combinations have been adopted as the first-line treatment for uncomplicated P. falciparum malaria in Cameroon since 2004. Methods: A total of 177 children aged six-months to 10 years with uncomplicated mono-infected falciparum malaria were randomized (1:1) to receive artesunate/sulphadoxine-pyrimethamine (AS/SP) or artesunate/amodiaquine (AS/AQ) pediatric tablets and followed up for 28 days according to the standard World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response (ACPR) on day 28. Results: The PCR corrected cure rate was high, overall (88.1%, 95% CI 83.1–93.1), 85.9% (95% CI 78.2–93.6), and 90.2% (95% CI 83.8–96.6) for AS/SP and AS/AQ, respectively. Twenty-one treatment failures were observed during follow-up, constituting one (4.6%), 14 (8.2%), and six (3.5%) early treatment failure (ETF), late clinical failure (LCF), and late parasitological failure (LPF), respectively. The drugs were well tolerated with no serious adverse events. Conclusions: Both AS/SP and AS/AQ are highly effective and well-tolerated treatments for uncomplicated P. falciparum malaria around the slope of Mount Cameroon

Association of candidate gene polymorphisms and TGF-beta/IL-10 levels with malaria in three regions of Cameroon: a case-control study.

BACKGROUND: Plasmodium falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical host genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity and improve vaccine development initiatives. METHODS: The effect of single nucleotide polymorphisms (SNPs) and plasma transforming growth factor beta (TGF-β) and interleukin 10 (IL-10) levels on malaria pathology was investigated in a case-control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Thirty-four malaria candidate polymorphisms, including the sickle cell trait (HbS), were assayed on the Sequenom iPLEX platform while plasma TGF-β and IL-10 levels were measured by sandwich ELISA. RESULTS: The study confirms the known protective effect of HbS against severe malaria and also reveals a protective effect of SNPs in the nitrogen oxide synthase 2 (NOS2) gene against malaria infection, anaemia and uncomplicated malaria. Furthermore, ADCY9 rs10775349 (additive G) and ABO rs8176746 AC individuals were associated with protection from hyperpyrexia and hyperparasitaemia, respectively. Meanwhile, individuals with the EMR1 rs373533 GT, EMR1 rs461645 CT and RTN3 rs542998 (additive C) genotypes were more susceptible to hyperpyrexia while both females and males with the rs1050828 and rs1050829 SNPs of G6PD, respectively, were more vulnerable to anaemia. Plasma TGF-β levels were strongly correlated with heterozygosity for the ADCY9 rs2230739 and HBB rs334 SNPs while individuals with the ABO rs8176746 AC genotype had lower IL-10 levels. CONCLUSION: Taken together, this study suggests that some rare polymorphisms in candidate genes may have important implications for the susceptibility of Cameroonians to severe malaria. Moreover using the uncomplicated malaria phenotype may permit the identification of novel pathways in the early development of the disease

MOESM2 of Malaria, helminths, co-infection and anaemia in a cohort of children from Mutengene, south western Cameroon

Additional file 3. Frequency distribution of age group, sex and anaemia status by helminth status. Proportion of participants who were helminth positive/negative by age group, gender and anaemia status at three time points

MOESM1 of Malaria, helminths, co-infection and anaemia in a cohort of children from Mutengene, south western Cameroon

Additional file 1. Number of malaria attacks by age group and gender. Proportion of participants with one attack vs multiple attacks by age group and gender

MOESM5 of Malaria, helminths, co-infection and anaemia in a cohort of children from Mutengene, south western Cameroon

Additional file 2. Frequency distribution of severity of anaemia by infection category. Proportion of participants with varying severity of anaemia by infection category (P-HL co-infection, Plasmodium only, helminths only)

Temporal distribution of ITN use, <i>P</i>. <i>falciparum</i> infection and malaria cases among participants from south western Cameroon.

<p>Temporal distribution of ITN use, <i>P</i>. <i>falciparum</i> infection and malaria cases among participants from south western Cameroon.</p

Reported ownership, quality and source of ITN of participants (n = 800) who started using bednets before and after the free distribution campaign.

<p>Reported ownership, quality and source of ITN of participants (n = 800) who started using bednets before and after the free distribution campaign.</p

Map of the study area.

<p>Localities on the slope of Mt. Cameroon included in the survey are indicated by blue triangles.</p

Association between human cytokine genetic polymorphisms and plasma cytokine levels.

<p>Plasma cytokine levels measured by ELISA were compared across human IL10 and <i>TNF</i> SNP genotypes of study participants. Of the three polymorphisms assayed for each cytokine, only the AA and TT genotypes of IL10 rs1800890 had lower plasma IL10 levels compared to their AT counterparts.</p