Publications by authors named "Sei Nishimura"

2 Publications

  • Page 1 of 1

The prevalence of glucose-6-phosphate dehydrogenase deficiency in Gambian school children.

Malar J 2014 Apr 17;13:148. Epub 2014 Apr 17.

Medical Research Council Unit, Atlantic Boulevard, Fajara, The Gambia.

Background: Primaquine, the only available drug effective against Plasmodium falciparum sexual stages, induces also a dose-dependent haemolysis, especially in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals. Therefore, it is important to determine the prevalence of this deficiency in areas that would potentially benefit from its use. The prevalence of G6PD deficiency by genotype and enzyme activity was determined in healthy school children in The Gambia.

Methods: Blood samples from primary school children collected during a dry season malaria survey were screened for G6PDd and malaria infection. Genotypes for allele mutations reported in the country; 376, 202A-, 968A- and 542 were analysed while enzyme activity (phenotype) was assayed using a semi-quantitative commercial test kit. Enzyme activity values were fitted in a finite mixture model to determine the distribution and calculate a cut-off for deficiency. The association between genotype and phenotype for boys and girls as well as the association between mutant genotype and deficient phenotype was analysed.

Results: Samples from 1,437 children; 51% boys were analysed. The prevalence of P. falciparum malaria infection was 14%. The prevalence of the 202A-, 968 and 542 mutations was 1.8%, 2.1% and 1.0%, respectively, and higher in boys than in girls. The prevalence of G6PDd phenotype was 6.4% (92/1,437), 7.8% (57/728) in boys and 4.9% (35/709) in girls with significantly higher odds in the former (OR 1.64, 95% CI 1.05, 2.53, p = 0.026). The deficient phenotype was associated with reduced odds of malaria infection (OR 0.77, 95% CI 0.36, 1.62, p = 0.49).

Conclusions: There is a weak association between genotype and phenotype estimates of G6PDd prevalence. The phenotype expression of deficiency represents combinations of mutant alleles rather than specific mutations. Genotype studies in individuals with a deficient phenotype would help identify alleles responsible for haemolysis.
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http://dx.doi.org/10.1186/1475-2875-13-148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999733PMC
April 2014

The effect of HLA polymorphisms on the recognition of Gag epitopes in HIV-1 CRF01_AE infection.

PLoS One 2012 27;7(7):e41696. Epub 2012 Jul 27.

Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.

Introduction: The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating.

Materials And Methods: 14 peptides based on consensus HIV-1 CRF01_AE amino acid sequences were designed for use in IFN-γ ELISpot assays and (51)Cr release assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico epitope-HLA prediction was performed.

Results: 29/66 (43.9%) patients recognized at least one peptide. In total 79 responses were seen against all 14 peptides. 28/79 (35.4%) of the responses were in patients with HLA alleles previously reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in individuals with HLA alleles previously reported to restrict epitopes of HIV clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not associated with HLA alleles previously known to restrict HIV epitopes. In silico epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%) were associated with HLA-C alleles. We further confirmed a novel HLA restriction of a previously identified HIV-1 Gag epitope [p24(122-130): PPIPVGDIY (PY9)] by HLA-B*40:01 with a standard (51)Cr release assay.

Discussion: CTL recognition sites in HIV-1 Gag were similar among different clades but the HLA restriction differed in Thai patients. This disparity in HLA restriction along different populations illustrated the importance of clade- and population-specific HLA analysis prior to CTL vaccine design.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0041696PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407236PMC
April 2013