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1.
Sci Rep ; 12(1): 7797, 2022 05 12.
Article in English | MEDLINE | ID: mdl-35551239

ABSTRACT

The molecular determinants of Plasmodium falciparum artemisinin resistance are the single nucleotide polymorphisms in the parasite's kelch propeller domain, pfk13. Validated and candidate markers are under surveillance in malaria endemic countries using artemisinin-based combination therapy. However, pfk13 mutations which may confer parasite artemisinin resistance in Africa remains elusive. It has therefore become imperative to report all observed pfk13 gene polymorphisms in malaria therapeutic efficacy studies for functional characterization. We herein report all novel pfk13 mutations observed only in the Ghanaian parasite population. In all, 977 archived samples from children aged 12 years and below with uncomplicated malaria from 2007 to 2017 were used. PCR/Sanger sequencing analysis revealed 78% (763/977) of the samples analyzed were wild type (WT) for pfk13 gene. Of the 214 (22%) mutants, 78 were novel mutations observed only in Ghana. The novel SNPs include R404G, P413H, N458D/H/I, C473W/S, R529I, M579T/Y, C580R/V, D584L, N585H/I, Q661G/L. Some of the mutations were sites and ecological zones specific. There was low nucleotide diversity and purifying selection at the pfk13 locus in Ghanaian parasite population. With increasing drug pressure and its consequent parasite resistance, documenting these mutations as baseline data is crucial for future molecular surveillance of P. falciparum resistance to artemisinin in Ghana.


Subject(s)
Antimalarials , Artemisinins , Malaria, Falciparum , Antimalarials/pharmacology , Antimalarials/therapeutic use , Artemisinins/pharmacology , Artemisinins/therapeutic use , Child , Drug Resistance/genetics , Ghana/epidemiology , Humans , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Plasmodium falciparum/genetics , Polymorphism, Single Nucleotide , Protozoan Proteins/genetics , Protozoan Proteins/pharmacology
2.
BMC Res Notes ; 12(1): 466, 2019 Jul 31.
Article in English | MEDLINE | ID: mdl-31366401

ABSTRACT

OBJECTIVE: HIV positive individuals infected with viral hepatitis B (HBV) or C (HCV) are at an increased risk of progression to kidney and liver failures. Therefore, prior to initiation of antiretroviral therapy, early diagnosis and initiation of appropriate treatment protocols are imperative for co-infected individuals. This study evaluated the prevalence of HBV and HCV, and extent of liver and renal dysfunction among 90 newly diagnosed HIV patients attending the Cape Coast Teaching Hospital HIV clinic. RESULTS: Levels of alanine aminotransferase, aspartate-platelet ratio index and estimated glomerular filtration rate were used respectively to diagnose hepatotoxicity, liver fibrosis and chronic kidney disease (CKD). Association analyses were evaluated by Pearson's Chi-square test or Fisher's exact test and considered significant at p < 0.05. Using rapid diagnostic tests, 75.6% (n = 68) had HIV1 mono-infection, 24.4% (n = 22) had HIV1/HBV co-infection while 0.0% (n = 0) had HIV1/HCV co-infection. The prevalence of hepatotoxicity, liver fibrosis, and CKD were 7.8% (n = 7), 2.2% (n = 2), and 15.5% (n = 14) respectively. Similar proportions of HIV1/HBV and HIV1 were diagnosed with liver fibrosis (p = 0.431). In relation to hepatotoxicity Grade, a high proportion of HIV1/HBV were diagnosed with Grade 2 (p = 0.042). Also, severely reduced kidney function (CKD stage 4) was observed in only HIV1/HBV (n = 2, 9.1%, p = 0.053).


Subject(s)
HIV Infections/physiopathology , Hepatitis B/physiopathology , Hepatitis C/physiopathology , Kidney/physiopathology , Liver Cirrhosis/physiopathology , Liver/physiopathology , Renal Insufficiency, Chronic/physiopathology , Adult , Alanine Transaminase/blood , Aspartic Acid/blood , Blood Platelets/pathology , Coinfection , Cross-Sectional Studies , Female , Ghana/epidemiology , Glomerular Filtration Rate , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/virology , Hepatitis B/diagnosis , Hepatitis B/epidemiology , Hepatitis B/virology , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C/virology , Humans , Kidney/metabolism , Kidney/virology , Liver/metabolism , Liver/virology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/virology , Liver Function Tests , Male , Middle Aged , Prevalence , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/virology
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