BACKGROUND The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS We used polymerase chain reaction–based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P = 0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P = 0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.)

Objective To examine cooking practices and 24-h personal and kitchen area exposures to fine particulate matter (PM2.5) and black carbon in cooks using biomass in Ghana. Methods Researchers administered a detailed survey to 421 households. In a sub-sample of 36 households, researchers collected 24-h integrated PM2.5 samples (personal and kitchen area); in addition, the primary cook was monitored for real-time PM2.5. All filters were also analyzed for black carbon using a multi-wavelength reflectance method. Predictors of PM2.5 exposure were analyzed, including cooking behaviors, fuel, stove and kitchen type, weather, demographic factors and other smoke sources. Results The majority of households cooked outdoors (55%; 231/417), used biomass (wood or charcoal) as their primary fuel (99%; 412/413), and cooked on traditional fires (77%, 323/421). In the sub-sample of 29 households with complete, valid exposure monitoring data, the 24-h integrated concentrations of PM2.5 were substantially higher in the kitchen sample (mean 446.8 μg/m3) than in the personal air sample (mean 128.5 μg/m3). Black carbon concentrations followed the same pattern such that concentrations were higher in the kitchen sample (14.5 μg/m3) than in the personal air sample (8.8 μg/m3). Spikes in real-time personal concentrations of PM2.5 accounted for the majority of exposure; the most polluted 5%, or 72 min, of the 24-h monitoring period accounted for 75% of all exposure. Two variables that had some predictive power for personal PM2.5 exposures were primary fuel type and ethnicity, while reported kerosene lantern use was associated with increased personal and kitchen area concentrations of black carbon. Conclusion Personal concentrations of PM2.5 exhibited considerable inter-subject variability across kitchen types (enclosed, semi-enclosed, outdoor), and can be elevated even in outdoor cooking settings. Furthermore, personal concentrations of PM2.5 were not associated with kitchen type and were not predicted by kitchen area samples; rather they were driven by spikes in PM2.5 concentrations during cooking. Personal exposures were more enriched with black carbon when compared to kitchen area samples, underscoring the need to explore other sources of incomplete combustion such as roadway emissions, charcoal production and kerosene use.

BackgroundArtesunate+amodiaquine (AS+AQ) and artemether-lumefantrine (AL) are now the most frequently recommended first line treatments for uncomplicated malaria in Africa. Artesunate+chlorproguanil-dapsone (AS+CD) was a potential alternative for treatment of uncomplicated malaria. A comparison of the efficacy and safety of these three drug combinations was necessary to make evidence based drug treatment policies.MethodsFive hundred and thirty-four, glucose-6-phosphate dehydrogenase (G6PD) normal children were randomised in blocks of 15 to the AS+AQ, AL or AS+CD groups. Administration of study drugs was supervised by project staff and the children were followed up at r home on days 1,2,3,7,14 and 28 post treatment. Parasitological and clinical failures and adverse events were compared between the study groups.Main FindingsIn a per-protocol analysis, the parasitological and clinical failure rate at day 28 post treatment (PCF28) was lower in the AS+AQ group compared to the AL or AS+CD groups (corrected for re-infections: 6.6% vs 13.8% and 13.8% respectively, p = 0.08; uncorrected: 14.6% vs 27.6% and 28.1% respectively, p = 0.005). In the intention to treat analysis, the rate of early treatment failure was high in all three groups (AS+AQ 13.3%; AL 15.2%; and AS+CD 9.3%, p = 0.2) primarily due to vomiting. However, the PCF28 corrected for re-infection was lower, though not significantly, in the AS+AQ group compared to the AL or the AS+CD groups (AS+AQ 18.3%; AL 24.2%; AS+CD 20.8%, p = 0.4) The incidence of adverse events was comparable between the groups.ConclusionsAS+AQ is an appropriate first line treatment for uncomplicated malaria in Ghana and possibly in the neighbouring countries in West Africa. The effectiveness of AL in routine programme conditions needs to be studied further in West Africa.Trial RegistrationClinicalTrials.gov NCT00119145

BackgroundClinical trials conducted in Africa often require substantial investments to support trial centres and public health facilities. Trial resources could potentially generate benefits for routine health service delivery but may have unintended consequences. Strengthening ethical practice requires understanding the potential effects of trial inputs on the perceptions and practices of routine health care providers. This study explores the influence of malaria vaccine trials on health service delivery in Ghana, Kenya and Burkina Faso.MethodsWe conducted: audits of trial inputs in 10 trial facilities and among 144 health workers; individual interviews with frontline providers (n=99) and health managers (n=14); and group discussions with fieldworkers (n=9 discussions). Descriptive summaries were generated from audit data. Qualitative data were analysed using a framework approach.ResultsFacilities involved in trials benefited from infrastructure and equipment upgrades, support with essential drugs, access to trial vehicles, and placement of additional qualified trial staff. Qualified trial staff in facilities were often seen as role models by their colleagues; assisting with supportive supervision and reducing facility workload. Some facility staff in place before the trial also received formal training and salary top-ups from the trials. However, differential access to support caused dissatisfaction, and some interviewees expressed concerns about what would happen at the end of the trial once financial and supervisory support was removed.ConclusionClinical trials function as short-term complex health service delivery interventions in the facilities in which they are based. They have the potential to both benefit facilities, staff and communities through providing the supportive environment required for improvements in routine care, but they can also generate dissatisfaction, relationship challenges and demoralisation among staff. Minimising trial related harm and maximising benefits requires careful planning and engagement of key actors at the outset of trials, throughout the trial and on its’ completion.

BackgroundDihydroartemisinin-piperaquine (DHA-PQ) is one of five WHO recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. However, little was known on its post-registration safety and effectiveness in sub-Saharan Africa. DHA-PQ provides a long post-treatment prophylactic effect against re-infection; however, new infections have been reported within a few weeks of treatment, especially in children. This paper reports the clinical outcomes following administration of DHQ-PQ in real-life conditions in public health facilities in Burkina Faso, Ghana, Mozambique, and Tanzania for the treatment of confirmed uncomplicated malaria.MethodsAn observational, non-comparative, longitudinal study was conducted on 10,591 patients with confirmed uncomplicated malaria visiting public health facilities within seven health and demographic surveillance system sites in four African countries (Ghana, Tanzania, Burkina Faso, Mozambique) between September 2013 and April 2014. Patients were treated with DHA-PQ based on body weight and followed up for 28 days to assess the clinical outcome. A nested cohort of 1002 was intensely followed up. Clinical outcome was assessed using the proportion of patients who reported signs and symptoms of malaria after completing 3 days of treatment.ResultsA total of 11,097 patients were screened with 11,017 enrolled, 94 were lost to follow-up, 332 withdrew and 10,591 (96.1 %) patients aged 6 months–85 years met protocol requirements for analysis. Females were 52.8 and 48.5 % were <5 years of age. Malaria was diagnosed by microscopy and rapid diagnostic test in 69.8 % and 29.9 %, respectively. At day 28, the unadjusted risk of recurrent symptomatic parasitaemia was 0.5 % (51/10,591). Most of the recurrent symptomatic malaria patients (76 %) were children <5 years. The mean haemoglobin level decreased from 10.6 g/dl on day 1 to 10.2 g/dl on day 7. There was no significant renal impairment in the nested cohort during the first 7 days of follow-up with minimal non-clinically significant changes noted in the liver enzymes.ConclusionDHA-PQ was effective and well tolerated in the treatment of uncomplicated malaria and provides an excellent alternative first-line ACT in sub-Saharan Africa.