Dataset Information

Effect of Drug Pressure on Promoting the Emergence of Antimalarial-Resistant Parasites among Pregnant Women in Ghana.

ABSTRACT: The continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped Plasmodium falciparum resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple IRN I- A/FG K GS/T pfdhfr/pfdhps haplotypes, including the pfdhps A581G and A613S/T mutations, was high at delivery among post-SP treatment isolates (18.2%) compared to those of first antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine [IPTp-SP]; 6.1%; P?=?0.03). Regarding the pfk13 marker gene, two nonsynonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast Asia. These mutations were predicted in silico to alter the stability of the pfk13 propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance of additional mutations associated with increased SP resistance as well as emergence of resistance against artemisinin derivatives.

SUBMITTER: Tornyigah B

PROVIDER: S-EPMC7269459 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Drug Pressure on Promoting the Emergence of Antimalarial-Resistant Parasites among Pregnant Women in Ghana.

Tornyigah Bernard B Coppée Romain R Houze Pascal P Kusi Kwadwo A KA Adu Bright B Quakyi Isabella I Coleman Nathaniel N Mama Atikatou A Deloron Philippe P Anang Abraham K AK Clain Jérôme J Tahar Rachida R Ofori Michael F MF Tuikue Ndam Nicaise N

Antimicrobial agents and chemotherapy 20200521 6

The continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped <i>Plasmodium falciparum</i> resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple <b ...[more]

PMID: 32179528

Similar Datasets

Project description:BACKGROUND Patient-performed blood pressure monitoring in pregnancy is rarely performed in low- and middle-income country settings, including Ghana. The clinical efficacy of home blood pressure monitoring relies on a pregnant patient being able to independently execute the correct steps to position and use a blood pressure monitor and to achieve accurate blood pressure measurements. OBJECTIVE This study aimed to (1) assess whether pregnant women can correctly use an automatic blood pressure monitor to check their blood pressure before and after a brief training and (2) determine whether blood pressure values measured by pregnant women using an automatic monitor are similar to values measured by a healthcare provider using a standard clinic monitor. STUDY DESIGN This was a cross-sectional study conducted at the Korle Bu Teaching Hospital, a tertiary hospital in Accra, Ghana. Participants were adult pregnant women presenting for their first prenatal care visit. Data collection was performed by 2 Ghanaian physicians. Information on demographics, obstetrical history, and past medical history was collected. A brief training was provided on the correct use of the blood pressure monitor, including a verbal script, annotated photographs, and a hands-on demonstration. Pre- and posttraining assessments using a 9-item checklist of correct preparation, position, and use of an automatic blood pressure monitor were performed. Following a modified British Hypertension Society protocol, a series of 4 blood pressure measurements were taken, alternating between provider performed using a clinic monitor and patient performed using an automatic monitor intended for individual use and validated in pregnancy. RESULTS Among 176 participants, the mean age was 31.5 years (±5.6), and 130 (73.9%) were multiparous. Regarding socioeconomic characteristics, 128 (72.7%) were married, 171 (97.2%) had public insurance, and 87 (49.7%) had completed ≤9 years of formal education. Regarding clinical blood pressure issues, 19 (10.9%) had a history of a hypertensive disorder in a previous pregnancy, and 6 (3.4%) had chronic hypertension. Before receiving any training, 21 participants (12.1%) performed all 9 steps correctly to prepare, position, and use the automatic blood pressure monitor. Comparing pretraining vs posttraining ability, statistically significant increases were seen in the correct performance of each step and the mean number of steps performed correctly (6.1±1.8 vs 9.0±0.2, respectively; P<.001) and proportion performing all 9 steps correctly (12.1% vs 96.6%, respectively; P<.001). The mean difference between doctor-performed and patient-performed blood pressure measurements was 5.6±4.8 mm Hg for systolic blood pressure values and 3.4±3.08 mm Hg for diastolic blood pressure values, with most differences within 5 mm Hg for both systolic blood pressure values (102/176 [58.0%]) and diastolic blood pressure values (141/176 [80.1%]). CONCLUSION After a brief training, pregnant women in Ghana demonstrated that they are able to use an automatic blood pressure monitor to check their blood pressure correctly and accurately.

Project description:BackgroundDrug resistance remains a concern for malaria control and elimination. The effect of interventions on its prevalence needs to be monitored to pre-empt further selection. We assessed the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs: sulfadoxine-pyrimethamine (SP), chloroquine (CQ) and artemisinin combination therapy (ACTs) after the scale-up of a vector control activity that reduced transmission.MethodsA total of 400 P. falciparum isolates from children under five years were genotyped for seventeen single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, pfdhps and pfk13 genes using polymerase chain reaction (PCR) and high resolution melting (HRM) analysis. These included 80 isolates, each randomly selected from cross-sectional surveys of asymptomatic infections across 2010 (baseline), 2011, 2012, 2013 (midline: post-IRS) and 2014 (endline: post-IRS) during the peak transmission season, when IRS intervention was rolled out in Bunkpurugu Yunyoo (BY) District, Ghana. The proportions of isolates with drug resistant alleles were assessed over this period.ResultsThere were significant decreases in the prevalence of pfdhfr- I51R59N108 haplotype from 2010 to 2014, while the decline in pfdhfr/pfdhps- I51R59N108G437 during the same period was not significant. The prevalence of lumefantrine (LM), mefloquine (MQ) and amodiaquine (AQ) resistance-associated haplotypes pfmdr1-N86F184D1246 and pfmdr1-Y86Y184Y1246 showed decreasing trends (z = -2.86, P = 0.004 and z = -2.71, P = 0.007, respectively). Each of pfcrt-T76 and pfmdr1-Y86 mutant alleles also showed a declining trend in the asymptomatic reservoir, after the IRS rollout in 2014 (z = -2.87, P = 0.004 and z = -2.65, P = 0.008, respectively). Similarly, Pyrimethamine resistance mediating polymorphisms pfdhfr-N108, pfdhfr-I51 and pfdhfr-R59 also declined (z = -2.03, P = 0.042, z = -3.54, P<0.001 and z = -4.63, P<0.001, respectively), but not the sulphadoxine resistance mediating pfdhps-G437 and pfdhps-F436 (z = -0.36, P = 0.715 and z = 0.41, P = 0.684, respectively). No mutant pfk13-Y580 were detected during the study period.ConclusionThe study demonstrated declining trends in the prevalence of drug resistant mutations in asymptomatic P. falciparum infections following transmission reduction after an enhanced IRS intervention in Northern Ghana.

Project description:The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by Plasmodium spp., which includes Apicoplast DNA polymerase and Plasmodium falciparum cysteine protease falcipain-2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti-malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand-protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross-correlation matrix showed positive outcomes for the protein-ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.

Dataset Information

Effect of Drug Pressure on Promoting the Emergence of Antimalarial-Resistant Parasites among Pregnant Women in Ghana.

Publications

Effect of Drug Pressure on Promoting the Emergence of Antimalarial-Resistant Parasites among Pregnant Women in Ghana.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets