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Ingasia L.A.,Kenya Medical Research Institute | Cheruiyot J.,Kenya Medical Research Institute | Okoth S.A.,Centers for Disease Control and Prevention | Okoth S.A.,Atlanta Research and Education Foundation Medical Center | And 2 more authors.
Infection, Genetics and Evolution | Year: 2016

Transmission intensity, movement of human and vector hosts, biogeographical features, and malaria control measures are some of the important factors that determine Plasmodium falciparum parasite genetic variability and population structure. Kenya has different malaria ecologies which might require different disease intervention methods. Refined parasite population genetic studies are critical for informing malaria control and elimination strategies. This study describes the genetic diversity and population structure of P. falciparum parasites from the different malaria ecological zones in Kenya. Twelve multi-locus microsatellite (MS) loci previously described were genotyped in 225 P. falciparum isolates collected between 2012 and 2013 from five sites; three in lowland endemic regions (Kisumu, Kombewa, and Malindi) and two in highland, epidemic regions (Kisii and Kericho). Parasites from the lowland endemic and highland epidemic regions of western Kenya had high genetic diversity compared to coastal lowland endemic region of Kenya [Malindi]. The Kenyan parasites had a mean genetic differentiation index (FST) of 0.072 (p = 0.011). The multi-locus genetic analysis of the 12 MS revealed all the parasites had unique haplotypes. Significant linkage disequilibrium (LD) was observed in all the five parasite populations. Kisumu had the most significant index of association values (0.16; p < 0.0001) whereas Kisii had the least significant index of association values (0.03; p < 0.0001). Our data suggest high genetic diversity in Kenyan parasite population with the exception of parasite from Malindi where malaria has been on the decline. The presence of significant LD suggests that there is occurrence of inbreeding in the parasite population. Parasite populations from Kisii showed the strongest evidence for epidemic population structure whereas the rest of the regions showed panmixia. Defining the genetic diversity of the parasites in different ecological regions of Kenya after introduction of the artemether-lumefantrine is important in refining the spread of drug resistant strains and malaria transmission for more effective control and eventual elimination of malaria in Kenya. © 2016. Source


Iriemenam N.C.,Centers for Disease Control and Prevention | Pandey J.P.,Medical University of South Carolina | Williamson J.,Centers for Disease Control and Prevention | Blackstock A.J.,Centers for Disease Control and Prevention | And 13 more authors.
PLoS ONE | Year: 2013

Immunoglobulin (Ig) GM and KM allotypes, genetic markers of γ and κ chains, are associated with humoral immune responsiveness. Previous studies have shown the relationships between GM6-carrying haplotypes and susceptibility to malaria infection in children and adults; however, the role of the genetic markers in placental malaria (PM) infection and PM with HIV co-infection during pregnancy has not been investigated. We examined the relationship between the gene polymorphisms of Ig GM6 and KM allotypes and the risk of PM infection in pregnant women with known HIV status. DNA samples from 728 pregnant women were genotyped for GM6 and KM alleles using polymerase chain reaction-restriction fragment length polymorphism method. Individual GM6 and KM genotypes and the combined GM6 and KM genotypes were assessed in relation to PM in HIV-1 negative and positive women, respectively. There was no significant effect of individual GM6 and KM genotypes on the risk of PM infection in HIV-1 negative and positive women. However, the combination of homozygosity for GM6(+) and KM3 was associated with decreased risk of PM (adjusted OR, 0.25; 95% CI, 0.08-0.8; P = 0.019) in HIV-1 negative women while in HIV-1 positive women the combination of GM6(+/-) with either KM1-3 or KM1 was associated with increased risk of PM infection (adjusted OR, 2.10; 95% CI, 1.18-3.73; P = 0.011). Hardy-Weinberg Equilibrium (HWE) tests further showed an overall significant positive F(is) (indication of deficit in heterozygotes) for GM6 while there was no deviation for KM genotype frequency from HWE in the same population. These findings suggest that the combination of homozygous GM6(+) and KM3 may protect against PM in HIV-1 negative women while the HIV-1 positive women with heterozygous GM6(+/-) combined with KM1-3 or KM1 may be more susceptible to PM infection. The deficit in heterozygotes for GM6 further suggests that GM6 could be under selection likely by malaria infection. Source


Lucchi N.W.,Centers for Disease Control and Prevention | Narayanan J.,Centers for Disease Control and Prevention | Karell M.A.,Atlanta Research and Education Foundation Medical Center | Xayavong M.,Centers for Disease Control and Prevention | And 5 more authors.
PLoS ONE | Year: 2013

There is a critical need for developing new malaria diagnostic tools that are sensitive, cost effective and capable of performing large scale diagnosis. The real-time PCR methods are particularly robust for large scale screening and they can be used in malaria control and elimination programs. We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. falciparum and the Plasmodium genus by real-time PCR. A total of 119 samples consisting of different malaria species and mixed infections were used to test the utility of the novel PET-PCR primers in the diagnosis of clinical samples. The sensitivity and specificity were calculated using a nested PCR as the gold standard and the novel primer sets demonstrated 100% sensitivity and specificity. The limits of detection for P. falciparum was shown to be 3.2 parasites/μl using both Plasmodium genus and P. falciparum-specific primers and 5.8 parasites/μl for P. ovale, 3.5 parasites/μl for P. malariae and 5 parasites/μl for P. vivax using the genus specific primer set. Moreover, the reaction can be duplexed to detect both Plasmodium spp. and P. falciparum in a single reaction. The PET-PCR assay does not require internal probes or intercalating dyes which makes it convenient to use and less expensive than other real-time PCR diagnostic formats. Further validation of this technique in the field will help to assess its utility for large scale screening in malaria control and elimination programs. Source


Singh P.P.,Regional Medical Research Center for Tribals | Singh P.P.,National Institute of Malaria Research Field Unit | Lucchi N.W.,Centers for Disease Control and Prevention | Blackstock A.,Centers for Disease Control and Prevention | And 4 more authors.
PLoS ONE | Year: 2012

Macrophage migration inhibitory factor (MIF) is a pluripotent factor produced by a variety of cells. It plays an important biological role in the regulation of pregnancy and has been shown to influence malaria pathogenesis. In this study, the levels of MIF in the peripheral, cord and placental intervillous blood (IVB) plasma collected from women residing in a malaria endemic region of Central India was determined and its association with malaria in pregnancy and birth outcomes was investigated. MIF levels were significantly different in IVB, peripheral, and cord plasma, with IVB plasma having the highest MIF levels and peripheral plasma having the lowest. Placental malaria positive women had significantly higher IVB plasma MIF levels than placental malaria negative women, but this relationship was not seen in peripheral or cord plasma MIF levels. In addition, the odds of stillbirth and low birth weight deliveries for the uppermost placental MIF quartile (irrespective of placental malaria status) was significantly higher than that of the lowest placental MIF quartile, supporting the hypothesis that elevated concentrations of placental MIF may be associated with an increased risk of adverse birth outcome. © 2012 Singh et al. Source

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