Ya-Ping Shi

Predicted and observed alleles of Plasmodium falciparum merozoite surface protein-1 (MSP-1), a potential malaria vaccine antigen

The 19-kDa antigenic domain of Plasmodium falciparum merozoite surface protein (MSP)-1 is a potential malaria vaccine candidate. Based on the amino acid substitution, four known alleles, E-TSR (PNG-MAD20 type), E-KNG (Uganda-PA type), Q-KNG (Wellcome type), and Q-TSR (Indo type) of this domain have been identified. Using single or double crossover recombinational events, we predicted the existence of additional alleles of this antigen. The presence of the predicted alleles was determined in parasite isolates from western Kenya, by undertaking a cross-sectional and a longitudinal study. Of the ten predicted alleles, we have revealed the presence of three new alleles: E-KSG-L (Kenya-1 type); E-KSR-L (Kenya-2 type); and E-KNG-F (Kenya-3 type). The results of this study suggest that it may be possible to predict the complexity of the genetic makeup of natural parasite populations.

Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission

Background: Little is known about the impact of HIV-1 group M subtypes on mother-to-child transmission (MTCT) of HIV-1 in African settings where multiple HIV-1 group M subtypes are co-circulating. Objective: To assess the role of subtype variation on MTCT. Methods: HIV-1-infected women attending an antenatal clinic in western Kenya were enrolled for a prospective study (1996–2000) of MTCT. HIV-1 subtype analysis of p24gag and gp41env identified potential recombinants, and their role in MTCT was determined. Results: Among 414 women for whom HIV-1 subtype and HIV transmission status were available, MTCT occurred in 80 (19.3%). MTCT rates were higher among women with subtype D compared with subtype A in either the gp41 region [31.6 versus 16.1%, relative risk (RR) 2.0, P = 0.002] or p24 region (29.9 versus 18.0%, RR 1.7, P = 0.02). Discordant subtype combinations were identified in 103 of the women (25.9%), and were associated with higher rates of MTCT (28.2 versus 17.0%, RR 1.7, P = 0.01). In multivariate analysis, women with subtype combinations D/D, D/A, and A/D had an increased risk of MTCT (adjusted odds ratios 3.5, 2.5, 6.2; P = 0.005, 0.05, and 0.0003, respectively) compared with A/A women after adjustment for maternal HIV viral load, placental malaria infection, episiotomy or perineal tear, and low birthweight. Conclusion: MTCT appears to be more common among mothers infected with subtype D compared with subtype A. Such differences in MTCT frequency may be caused by altered cellular tropism for placental cell types.

Genetic diversity and high proportion of intersubtype recombinants among HIV type 1-infected pregnant women in Kisumu, western Kenya.

The high genetic diversity of HIV-1 continues to complicate effective vaccine development. To better understand the extent of genetic diversity, intersubtype recombinants and their relative contribution to the HIV epidemic in Kenya, we undertook a detailed molecular epidemiological investigation on HIV-1-infected women attending an antenatal clinic in Kisumu, Kenya. Analysis of gag-p24 region from 460 specimens indicated that 310 (67.4%) were A, 94 (20.4%) were D, 28 (6.1%) were C, 9 (2.0%) were A2, 8 (1.7%) were G, and 11 (2.4%) were unclassifiable. Analysis of the env -gp41 region revealed that 326 (70.9%) were A, 85 (18.5%) D, 26 (5.7%) C, 9 (2.0%) each of A2 and G, 4(0.9%) unclassifiable, and 1 (0.2%) CRF02_AG. Parallel analyses of the gag-p24 and env-gp41 regions indicated that 344 (74.8%) were concordant subtypes, while the remaining 116 (25.2%) were discordant subtypes. The most common discordant subtypes were D/A (40, 8.7%), A/D (27, 5.9%), C/A (11, 2.4%), and A/C (8, 1.7%). Further analysis of a 2.1-kb fragment spanning the gag-pol region from 38 selected specimens revealed that 19 were intersubtype recombinants and majority of them were unique recombinant forms. Distribution of concordant and discordant subtypes remained fairly stable over the 4-year period (1996-2000) studied. Comparison of amino acid sequences of gag-p24 and env-gp41 regions with the subtype A consensus sequence or Kenyan candidate vaccine antigen (HIVA) revealed minor variations in the immunodominant epitopes. These data provide further evidence of high genetic diversity, with subtype A as the predominant subtype and a high proportion of intersubtype recombinants in Kenya.

Effect of haematinic supplementation and malaria prevention on maternal anaemia and malaria in western Kenya

Objectiveu2002 To evaluate the effect of routine antenatal haematinic supplementation programmes and intermittent preventive treatment (IPT) with sulphadoxine–pyrimethamine (SP) in Kenya.