Browsing by Author "Koram, K. A."
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Item Frequent and persistent, asymptomatic plasmodium falciparum infections in african infants, characterized by multilocus genotyping.(2001-03) Franks, S.; Koram, K. A.; Wagner, G. E.; Tetteh, K.; McGuinness, D.; Wheeler, J. G.; Nkrumah, F.; Ranford-Cartwright, L.; Riley, E.M.To determine the duration and complexity of naturally acquired Plasmodium falciparum infections in small children, a longitudinal cohort study of 143 newborns was conducted in coastal Ghana. On average, children experienced 2 episodes of infection in their first 2 years of life, the median duration of an asymptomatic infection was <4 weeks, and estimates of the mean number of parasite genotypes per infection were 1.15-2.28. Nevertheless, 40% of the children experienced infections lasting ≤12 weeks, and both the duration and complexity of infections increased with age. The longest period of continual infection was 64 weeks, and the maximum persistence of a single parasite genotype was 40 weeks. Thus, malaria infections in infants <5 months old tend to be asymptomatic and rapidly cleared; persistent asymptomatic parasitemia is more common in children >5 months old. The ability of very young children to clear or control malaria infections indicates the presence of effective innate or immune antiparasite mechanisms.Item Haplotype analyses of haemoglobin C and haemoglobin S and the dynamics of the evolutionary response to malaria in kassena-nankana district of Ghana.(2012-04) Ghansah, A.; Rockett, K.A.; Clark, T. G.; Wilson, M.D.; Koram, K. A.; Oduro, A. R.; Amenga-Etego, L.; Anyorigiya, T.; Hodgson, A.; Milligan, P.; Rogers, W.O.; Kwiatkowski, D.P.Background: Haemoglobin S (HbS) and C (HbC) are variants of the HBB gene which both protect against malaria. It is not clear, however, how these two alleles have evolved in the West African countries where they co-exist at high frequencies. Here we use haplotypic signatures of selection to investigate the evolutionary history of the malaria-protective alleles HbS and HbC in the Kassena-Nankana District (KND) of Ghana. Methodology/Principal Findings: The haplotypic structure of HbS and HbC alleles was investigated, by genotyping 56 SNPs around the HBB locus. We found that, in the KND population, both alleles reside on extended haplotypes (approximately 1.5 Mb for HbS and 650 Kb for HbC) that are significantly less diverse than those of the ancestral HbA allele. The extended haplotypes span a recombination hotspot that is known to exist in this region of the genome Significance: Our findings show strong support for recent positive selection of both the HbS and HbC alleles and provide insights into how these two alleles have both evolved in the population of northern Ghana. © 2012 Ghansah et al.Item Lack of gender-specific antibody recognition of products from domains of a var gene implicated in pregnancy-associated plasmodium falciparum malaria.(2003-07) Jensen, A. T. R.; Zornig, H. D.; Buhmann, C.; Salanti, A.; Koram, K. A.; Riley, E. M.; Theander, T.G.; Hviid, L.; Staalsoe, T.Gender-specific and parity-dependent acquired antibody recognition is characteristic of variant surface antigens (VSA) expressed by chondroitin sulfate A (CSA)-adherent Plasmodium falciparum involved in pregnancy-associated malaria (PAM). However, antibody recognition of recombinant products of a specific VSA gene (2O2var1) implicated in PAM and transcribed by a CSA-adhering parasite line did not have these characteristics. Furthermore, we could not demonstrate preferential transcription of 2O2var1 in the CSA-adhering line versus the unselected, parental isolate. Our data call for circumspection regarding the molecular identity of the parasite ligand mediating adhesion to CSA in PAM.Item Mutations in plasmodium falciparum chloroquine resistance transporter and multidrug resistance genes, and treatment outcomes in Ghanaian children with uncomplicated malaria.(2007-02) Duah, N. O.; Wilson, M. D.; Ghansah, A.; Abuaku, B.; Edoh, D.; Quashie, N. B.; Koram, K. A.The association between the clinical outcome of chloroquine treatment and mutations in the putative Plasmodium falciparum chloroquine resistance transporter (Pf crt) gene at codon 76 and multidrug resistance gene 1 (Pfmdr1) at codon 86 were investigated among 406 children with uncomplicated malaria presenting at five sentinel health centres in Ghana. Presence of mutations in isolates taken at pre-treatment and on day of recurrence of parasites was detected using PCR followed by RFLP techniques. The prevalence of Pf crt T76 mutants was 80% at Hohoe, 46% at Navrongo, 98% at Tarkwa, 61% at Sunyani and 46% at Yendi. The prevalence of the mutant Pf mdr1 at Hohoe, Navrongo, Tarkwa, Sunyani and Yendi were 78, 58, 95, 53 and 42%, respectively. Significant association between the Pf crt mutation and treatment outcome was observed at Hohoe and Sunyani (p < 0.05), but not at Navrongo, Tarkwa or Yendi (p > 0.05). Similarly, a statistical significant association between Pf mdr1 86 and treatment failures was observed at Hohoe and Sunyani (p < 0.05) but not at the other three sites. A positive correlation was found between mutant Pf crt prevalence only and treatment failures with a Spearman's ρ-value of 0.872 and a p-value=0.027. All parasite isolates from samples taken at recrudescence from patients with chloroquine treatment failures were found to have both Pf crt and Pf mdr mutations. © 2007 Oxford University Press.Item Studies on Genetic Mutations in Plasmodium Falciparum Strains Associated With 4- Aminoquinolines (Chloroquine) and Pyrimethamine Sulphadoxine (Fansidar) Resistance in Ghanaian Malaria Patients.(University of Ghana, 2001-09) Duah, N. O.; Wilson, M. D.; Koram, K. A.; Edoh, D.; University of Ghana, College of Basic and Applied Sciences, School of Biological Sciences, Department of Animal Biology and Conservation Science (DABCS)The malaria drug policy for Ghana is chloroquine, Fansidar and quinine as the first line, second line and third line drugs respectively. However, the burden of malaria has been complicated by the emergence of resistance especially to chloroquine, which is a cheap and effective drug. It has therefore become imperative that the levels of resistance of Plasmodium falciparum to anti-malarial drugs (chloroquine and Fansidar) in Ghana be established and the information used to develop an appropriate drug policy for effective case management. This present study therefore used molecular techniques, mostly, polymerase chain reaction (PCR) to detect and characterise mutations in the putative P. falciparum transporter gene (pfcrt) and P. falciparum multi-drug resistance gene (pfmdrl) that are known from previous studies to be associated with chloroquine resistance. Mutations in the dihydrofolate reductase g ene ( dhfr) and dihydropteroate synthase gene (dhps) that are associated with pyrimethamine-sulphadoxine (Fansidar) resistance were also studied. Children aged 5 years and below diagnosed as having uncomplicated malaria were recruited at two sentinel hospitals in Ghana (Hohoe and Navrongo) for the study with an informed consent from parents or guardians. Blood films obtained from the patients were examined for the presence of malaria parasites before treatment (Day 0) and then on Days 7 and 14 after treatment. Filter paper blood blots were also obtained at the same time, for use in PCR to detect the mutations. In addition to these, in-vitro chloroquine sensitivity test was performed on P. falciparum isolates from 26 patients. The in vivo studies revealed that 62% and 31 % of the patients from Hohoe and Navrongo respectively were resistant to chloroquine. The classification of resistance according to parasitological clearance at Hohoe was 55%, 33% and 13% for RI, RII and RIII levels respectively; it was 43%, 33% and 23% respectively at Navrongo. T he b aseline p revalence o f t he p fc r t 76 and p fm d rl 86 mutations were 82.5% and 82.0% in Hohoe and 43.8% and 61.5% in Navrongo. An association between pfcrt and p fm d r l mutations and clinical outcome was observed a t Hohoe (odds ratio = 12.40, p = 0.0001) but not at Navrongo (odds ratio = 1.16, p = 0.75). The baseline prevalence of the quintuple mutations of dhfr and dhps were 31.1% and 1.04% for Hohoe and Navrongo respectively. The in-vitro results showed that 7 of the 26 isolates were resistant to chloroquine with an IC50 value of 1.5xl0'6 mol/litre. The results from this study suggest that mutations in pfcrt and p fm d rl can be used to predict the outcome of chloroquine treatment at Hohoe but not at Navrongo. The observed differences in the pfcrt and pfmdrl prevalence rates and in the association between genetic mutations and treatment outcome, is thought to be due to differences in drug pressure at the two areas. The relatively high prevalence of the quintuple mutations of dhfr and dhps observed at Hohoe gives an idea of the use of Fansidar whilst is the contrary for Navrongo.