PATH (GAVI Alliance grant) and Merck.

GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.

BackgroundConsidering the natural history of malaria of continued susceptibility to infection and episodes of illness that decline in frequency and severity over time, studies which attempt to relate immune response to protection must be longitudinal and have clearly specified definitions of immune status. Putative vaccines are expected to protect against infection, mild or severe disease or reduce transmission, but so far it has not been easy to clearly establish what constitutes protective immunity or how this develops naturally, especially among the affected target groups. The present study was done in under six year old children to identify malaria antigens which induce antibodies that correlate with protection from Plasmodium falciparum malaria.MethodsIn this longitudinal study, the multiplex assay was used to measure IgG antibody levels to 10 malaria antigens (GLURP R0, GLURP R2, MSP3 FVO, AMA1 FVO, AMA1 LR32, AMA1 3D7, MSP1 3D7, MSP1 FVO, LSA-1and EBA175RII) in 325 children aged 1 to 6 years in the Kassena Nankana district of northern Ghana. The antigen specific antibody levels were then related to the risk of clinical malaria over the ensuing year using a negative binomial regression model.ResultsIgG levels generally increased with age. The risk of clinical malaria decreased with increasing antibody levels. Except for FMPOII-LSA, (p = 0.05), higher IgG levels were associated with reduced risk of clinical malaria (defined as axillary temperature ≥37.5°C and parasitaemia of ≥5000 parasites/ul blood) in a univariate analysis, upon correcting for the confounding effect of age. However, in a combined multiple regression analysis, only IgG levels to MSP1-3D7 (Incidence rate ratio = 0.84, [95% C.I.= 0.73, 0.97, P = 0.02]) and AMA1 3D7 (IRR = 0.84 [95% C.I.= 0.74, 0.96, P = 0.01]) were associated with a reduced risk of clinical malaria over one year of morbidity surveillance.ConclusionThe data from this study support the view that a multivalent vaccine involving different antigens is most likely to be more effective than a monovalent one. Functional assays, like the parasite growth inhibition assay will be necessary to confirm if these associations reflect functional roles of antibodies to MSP1-3D7 and AMA1-3D7 in this population.

SummaryThe study examined the efficacy of chloroquine (CQ), amodiaquine (AQ) and sulphadoxinepyrimethamine (SP) for the treatment of uncomplicated Plasmodium falciparum malaria in Ghana.A total of 351 children were randomized to receive either of the three study drugs. Patients were evaluated using the WHO 14-day in vivo antimalarial testing guidelines. The 14-day adequate clinical and parasitological response analysis revealed that CQ, 46.7% (95% CI 37.5, 56.0) has the least efficacy compared with AQ, 86.1% (95% CI 78.3, 91.8) and SP, 77.6% (95% CI 68.9, 84.8). Late parasite failures were also lower and similar in the AQ and SP (9.6% and 10.3%) than in the CQ (32.5%) group. However, CQ and AQ groups showed better fever clearance compared with SP throughout except for day 7 and after when possibly due to its significant late clinical failures, clearance by CQ was lower. Our findings suggest that CQ is no longer useful in Ghana and should be replaced as a first-line treatment of malaria. Replacement of CQ preferably with AQ combination treatment will be an effective and an affordable alternative for the treatment of uncomplicated malaria.

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Background Malaria remains a major public health problem, especially in sub-Sahara African countries. The Malaria Control Program of Ghana has implemented Seasonal Malaria Chemoprevention (SMC) intervention in the Upper West Region in 2015. This preventive drug has been recommended by WHO as very safe and effective in preventing malaria in children under five years. This study assessed community acceptability of the SMC intervention in the Lawra district of Northern Ghana. Methodology This was a qualitative study where focus group discussions and in-depth interviews were conducted with community-based health volunteers and parents whose children received the SMC drug. Purposive sampling method was used to select study participants. The interviews were recorded with consent of study participants. All interviews were transcribed and coded into emergent themes using Nvivo 10 software before thematic content analysis. Results Study participants perceived that the introduction of the SMC intervention in the area had helped to reduce the prevalence of malaria among children less than five years of age. Parents held the view that the drug was very good in preventing malaria. The results also showed high acceptability of the SMC intervention by parents and other community members. Parents reported that they were willing to allow their children to receive the drug and wished the intervention could continue in the district for children to continue to benefit. Nonetheless, negative attitude on the part of few parents made them not to allow their children to receive the drug. Conclusion The interpretation of our data showed high acceptability of the SMC by stakeholders in the study area. However, intensive and continued health education on the benefits of the SMC drug could help to further improve acceptability of the program.

Background In Sahelian Africa, the risk of malaria increases with the arrival of the rains, particularly in young children. Following successful trials, the World Health Organization (WHO) recommended the use of seasonal malaria chemoprevention (SMC) in areas with seasonal peak in malaria cases. This study evaluated the pilot implementation of SMC in Northern Ghana. Methods Fourteen communities each serving as clusters were selected randomly from Lawra District of Upper West Region as intervention area and West Mamprusi District in the Northern Region as the non-intervention area. The intervention was undertaken by the National Malaria Control Programme in collaboration with regional health directorates using sulfadoxine-pyrimethamine plus amodiaquine and standard WHO protocols. Before and after surveys for malaria parasitaemia and haemoglobin levels as well as monitoring for malaria morbidity and mortality were undertaken. Results At the end of the intervention, participant retention was 92.9% (697/731) and 89.5% (634/708) in the intervention and the non-intervention areas, respectively. The proportion of children with asexual parasites reduced by 19% (p = 0.000) in the intervention and increased by 12% (p = 0.000) in the non-intervention area. Incidence rates of severe malaria were 10 and 20 per 1000 person-years follow up in the intervention and comparison areas, respectively with P.E of 45% (p = 0.62). For mild malaria, it was 220 and 170 per 1000 person-years in intervention and comparison area, respectively with PE of - 25% (p = 0.31). The proportion of children with anaemia defined as Hb< 11.0 g/dl reduced from 14.2% (52.8–38.6%) in the intervention area as compared to an increase of 8.1% (54.5% to 62.6) the non-intervention arm, Mean Hb reduced by 0. 24 g/dl (p = 0.000) in the non-intervention area and increased of 0.39 g/dl (p = 000) in the intervention area. Conclusions The feasibility and effectiveness of SMC introduction in Northern Ghana was demonstrated as evidenced by high study retention, reduction in malaria parasitaemia and anaemia during the wet season.

Although the use of artesunate-amodiaquine treatment is growing in Africa, data on its effectiveness are limited. In only the second published comparison of supervised and unsupervised treatments with this combination, Ghanaian children with uncomplicated malaria have recently been investigated in an open-label, randomized, comparative study. Children aged 6-120 months attending the Navrongo War Memorial hospital between November 2005 and December 2006 were enrolled if they had uncomplicated Plasmodium falciparum malaria and at least one of their parents/guardians gave their informed consent. Overall, 638 patients were screened, 357 were found to have P. falciparum infection, and 308 of these satisfied the other selection criteria and were enrolled. The subjects were divided randomly into two treatment arms. All the children were scheduled to receive 10 mg amodiaquine/kg and 4 mg artesunate/kg daily for 3 days but only 154 (the 'supervised') were given all their treatments in hospital, with each dose directly observed. Although the other 154 children (the 'unsupervised') were given their first dose in hospital, under supervision, they were then sent home with the tablets they required to complete treatment. Study participation lasted for 28 days, with follow-up on days 3, 7, 14, 21 and 28. During follow-up, axillary temperatures, any emergent signs and symptoms, and concomitant drug consumption were recorded and haemoglobin concentrations and malarial parasitaemias and gametocytaemias were measured. All but seven of the 308 subjects completed the study. At enrolment the subjects had a mean age of 45.0 months, a mean weight of 14.8 kg, a mean axillary temperature of 37.9 degrees C and a geometric mean parasitaemia of 11,367 asexual stages/microl. About 55% of the children investigated were girls. There were no significant baseline difference between the two treatment arms. Although there was also no difference in the clearance of fever and parasitaemia between the two arms by day 14, a supervised child was significantly more likely to show an adequate clinical and parasitological response, by day 21 (91.3% v. 84.1%; P= 0.05) or day 28 (80.0% v. 64.9%; P<0.01), than an unsupervised child. The reported adverse effects following treatment and the trend in haemoglobin recovery were, however, similar in the two arms. Although artesunate-amodiaquine appeared very effective in the treatment of uncomplicated P. falciparum malaria in children, whether supervised or not, it appears that supervised treatment provided stronger prevention against re-infection and recrudescence. At least in the present study, treatment at home, without medical supervision, probably led to relatively poor compliance.