Division of Infectious Diseases, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
Canadian Medical Association Journal (Impact Factor: 5.81). 06/2004; 170(11):1693-702.
Source: PubMed Central

ABSTRACT Malaria is a parasitic infection of global importance. Although relatively uncommon in developed countries, where the disease occurs mainly in travellers who have returned from endemic regions, it remains one of the most prevalent infections of humans worldwide. In endemic regions, malaria is a significant cause of morbidity and mortality and creates enormous social and economic burdens. Current efforts to control malaria focus on reducing attributable morbidity and mortality. Targeted chemoprophylaxis and use of insecticide-treated bed nets have been successful in some endemic areas. For travellers to malaria-endemic regions, personal protective measures and appropriate chemoprophylaxis can significantly reduce the risk of infection. Prompt evaluation of the febrile traveller, a high degree of suspicion of malaria, rapid and accurate diagnosis, and appropriate antimalarial therapy are essential in order to optimize clinical outcomes of infected patients. Additional approaches to malaria control, including genetic manipulation of mosquitoes and malaria vaccines, are areas of ongoing research.

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    ABSTRACT: The antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials. In this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3α and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. The proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1*01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein. HLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.
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    ABSTRACT: Although microscopic examination of Giemsa-stained blood smears remains the gold standard for diagnosis of malaria, molecular detection using polymerase chain reaction (PCR) is becoming increasingly popular. Due to discrepant PCR and microscopy results, we aimed to optimize our detection assays for P. malariae and P. ovale by sequencing the 18S rRNA region and developing a new primer and probe set for real time PCR (qPCR). Clinical specimens positive for P. malariae (n=15) or P. ovale (n=33) underwent amplification and sequencing of the 18S rRNA region. Based on sequence discrepancies between our current primer/probe and clinical isolates, degenerate P. ovale primer and probe were developed to determine if performance characteristics improved. Reference standard ("gold" standard) was microscopy. No 18S sequence heterogeneity was observed among the P. malariae isolates, and sensitivity and specificity of our current P. malariae qPCR assay was 100%. Compared to microscopy, the sensitivity and specificity of our current P. ovale qPCR assay were 72.7% and 100%, respectively. Five single nucleotide polymorphisms (SNPs) were identified in P. ovale. Sensitivity of the new P. ovale assay increased to 100% with 100% specificity. We therefore improved the performance characteristics of our P. ovale molecular detection assay through development of a degenerate primer and probe set which accommodates 18S SNPs among the 2 sub-species of P. ovale. Given the sub-optimal sensitivity of rapid diagnostic tests for non-falciparum malaria, and the typically low parasitemia of P. malariae and P. ovale, a well performing confirmatory molecular assay is imperative for clinical laboratories.
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