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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