Short Report: Association Between Chloroquine and Amodiaquine Resistance and Allelic Variation in the Plasmodium Falciparum Multiple Drug Resistance 1 Gene and the Chloroquine Resistance Transporter Gene in Isolates from the Upper Nile in Southern Sudan.

Amodiaquine, a 4-aminoquinoline compound, is being considered as an alternative to chloroquine and pyrimethamine/sulfadoxine where resistance in Plasmodium falciparum to both drugs has been selected. Although amodiaquine is more potent than chloroquine, its effectiveness is reduced in areas where chloroquine resistance is high. We report an association of the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multiple drug resistance 1 (pfmdr1) gene, two chloroquine resistance markers, with chloroquine and amodiaquine efficacy in vivo in southern Sudan. The data show that the allele of the pfcrt gene with a lysine to threonine change at codon 76 is strongly associated with both chloroquine and amodiaquine resistance. No such association was observed with the pfmdr1 gene

Variation in Quantity of Heat Produced from Charcoal of Prosopis Africana, Tectona Grandis, and Burkea Africana Wood Species

Variation in the quantity of heat produced from the charcoal of Prosopis africana, Tectona grandis, and Burkea africana wood species was investigated. This was done to determine whether differences in the species and parts of the trees have significant effect on quantity of heat from their charcoal samples. Data were collected using the copper calorimeter, a thermometer, an air tight burner and a weight balance. The results showed a gradual decrease in the quantity of heat produced as combustion time increased from 10 40 minutes in all wood species. Significant differences (p<0.05) in the quantity of heat produced both within and between the charcoal of all the wood species were also observed. Further investigation revealed that the base of all the samples produced more heat (p<0.05) within species followed by the bole and the crown. The between wood species showed that Prosopis africana produced more heat followed by Burkea africana and Tectona grandis which may be attributed to the impact of density as it is more concentrated at the base than any other part of the wood

The Administrative factors hindering the efficient accountability of public officers in fulfilling public functions

Submitted in partial fulfillment of the requirements of the Bachelor of Laws Degree, Strathmore University Law SchoolThis dissertation focuses on the regulation and holding to account of public officers with regard to fulfilling public functions, which can be understood as the responsibility taken up by the state to provide public services to its citizens. There has been an exponential increase in cases reported of public officers mismanaging and embezzling public funds in Kenya, leading to inefficient provision of services to the public and a reduction in the socio economic welfare of the citizens due to mismanagement of tax payer’s money. This research paper outlines the administrative measures stipulated by law with respect to policies made and the institutions established in regulating, monitoring, investigating and prosecuting actors. Moreover, the dissertation seeks to assert the real issues that have inhibited the efficient regulation and holding to account of public officers by providing a historical account of the role of regulatory bodies mandated with the role of investigating corrupt public officers in public office. The research paper further highlights the National Youth Service corruption scandal as its case study, providing the facts of the case and thereafter providing new reforms/approaches that can be implemented in the ongoing probing of the public officers accused of the corruption offences. Inherently, this research paper seeks to outline the statutory loopholes in the law with respect to regulation of public officers. It also outlines general institutional measures, internal and external, necessary to maintain efficiently provided public functions guided by the principles set out in the constitution with respect to leadership, integrity and the rule of la

Novel contributions to understanding the mechanism of folate transport and anti-folate resistance in Plasmodium falciparum

The primary focus of the PhD thesis has exclusively been on studies on Plasmodium falciparum with a remit to build a clear understanding on some of the critical and relevant questions relating to folates transport and antifolates resistance. The direction of this work has been constructed on the following themes of interest; 1. The Influence of folate pathway substrates on the In Vitro activities of antifolate drugs. 2. Functional characterization of heterologously expressed putative folate transporters in the Xenopus laevis oocyte. 3. Transcriptional analysis of putative folate transporter genes

Efficacy of chloroquine, sulphadoxine-pyrimethamine and amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria in Kajo Keji county, Sudan.

To provide advice on the rational use of antimalarial drugs, Médecins Sans Frontières conducted a randomized, an open label efficacy study in Kajo Keji, an area of high transmission of malaria in southern Sudan. The efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) were measured in a 28-day in vivo study, with results corrected by PCR genotyping. Of 2010 children screened, 115 children aged 6-59 months with uncomplicated Plasmodium falciparum malaria were randomized into each group to receive a supervised course of treatment. Of these, 114, 103 and 111 were analysed in the CQ, SP and AQ groups, respectively. The overall parasitological failure rates at day 28 were 93.9% [95% confidence interval (CI) 87.3-97.3] for CQ, 69.9% (95% CI 60.0-78.3) for SP, and 25.2% (95% CI 17.7-34.5) for AQ. These results provide important missing data on antimalarial drug efficacy in southern Sudan. They indicate that none of the drugs could be used in monotherapy and suggest that even in combination with artemisinin, cure rates might not be efficacious enough. We recommend a combination of artemether and lumefantrine as first-line treatment for uncomplicated P. falciparum malaria cases in Kajo Keji county

Chloroquine-resistance molecular markers (Pfcrt T76 and Pfmdr-1 Y86) and amodiaquine resistance in Burkina Faso.

We investigated the relationship between the two main molecular markers for chloroquine resistance (Pfcrt T76 and Pfmdr-1 Y86) and the clinical efficacy of amodiaquine in Burkina Faso. Before treatment, the prevalence of Pfcrt T76, Pfmdr-1 Y86 or both mutations in the same infection was significantly higher in patients who experienced a recrudescence than in those who successfully responded to the treatment. Therefore, these two molecular markers could be useful in monitoring amodiaquine resistance, particularly in countries where this drug is used in combination with artesunate as first- or second-line treatment

Molecular monitoring of the Leu-164 mutation of dihydrofolate reductase in a highly sulfadoxine/pyrimethamine-resistant area in Africa

The selection of point mutation at codon 164 (from isoleucine to leucine) of the dihydrofolate reductase (DHFR) enzyme in Plasmodium falciparum is associated with high sulfadoxine /pyrimethamine (SP) resistance. Using the yeast expression system that allows the detection of dhfr allele present at low level, the presence of this mutation had previously been reported between 1998–1999 in Muheza, Tanzania, an area of high SP resistance. Eighty five P. falciparum isolates, obtained from the same area between 2002 and 2003, were analysed for the presence of Leu-164 mutation, using standard protocol based on PCR-RFLP. None of the isolates had the Leu-164 mutation

Chloroquine resistance before and after its withdrawal in Kenya

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance

<p>Abstract</p> <p>Background</p> <p>Daily trimethoprim-sulfamethoxazole (TS) protects against malaria, but efficacy may be diminished as anti-folate resistance increases. This study assessed the incidence of falciparum malaria and the prevalence of resistance-conferring <it>Plasmodium falciparum </it>mutations in HIV-infected children receiving daily TS and HIV-uninfected children not taking TS.</p> <p>Materials and methods</p> <p>Subjects were 292 HIV-infected and 517 uninfected children from two cohort studies in Kampala, Uganda observed from August 2006 to December 2008. Daily TS was given to HIV-infected, but not HIV-uninfected children and all participants were provided an insecticide-treated bed net. Standardized protocols were used to measure the incidence of malaria and identify markers of antifolate resistance.</p> <p>Results</p> <p>Sixty-five episodes of falciparum malaria occurred in HIV-infected and 491 episodes in uninfected children during the observation period. TS was associated with a protective efficacy of 80% (0.10 vs. 0.45 episodes per person year, p < 0.001), and efficacy did not vary over three consecutive 9.5 month periods (81%, 74%, 80% respectively, p = 0.506). The prevalences of <it>dhfr </it>51I, 108N, and 59R and <it>dhps </it>437G and 540E mutations were each over 90% among parasites infecting both HIV-infected and uninfected children. Prevalence of the <it>dhfr </it>164L mutation, which is associated with high-level resistance, was significantly higher in parasites from HIV-infected compared to uninfected children (8% vs. 1%, p = 0.001). Sequencing of the <it>dhfr </it>and <it>dhps </it>genes identified only one additional polymorphism, <it>dhps </it>581G, in 2 of 30 samples from HIV-infected and 0 of 54 samples from uninfected children.</p> <p>Conclusion</p> <p>Despite high prevalence of known anti-folate resistance-mediating mutations, TS prophylaxis was highly effective against malaria, but was associated with presence of <it>dhfr </it>164L mutation.</p