scholarly journals Absence of Plasmodium falciparum artemisinin resistance gene mutations eleven years after the adoption of artemisinin-based combination therapy in Nigeria

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Moses Ikegbunam ◽  
Johnson A. Ojo ◽  
Kossiwa Kokou ◽  
Ugonna Morikwe ◽  
Chukwuemeka Nworu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Gene Mutations ◽  
Artemisinin Resistance ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Cross Sectional ◽  
Two Samples ◽  
Group A

Abstract Background The occurrence of artemisinin resistance (ART)-associated polymorphism of Plasmodium falciparum K13-propeller (pfk13) gene before and after the introduction of artemisinin-based combination therapy (ACT) in two regions of Nigeria was investigated in this study. Regular surveillance is necessary to make a definite conclusion on the emergence and pattern of possible resistance to ART. Methods This cross-sectional study was carried out in the Southwestern and Southeastern geopolitical zones of Nigeria. A total of 150, 217, and 475 participants were enrolled for the study in the Southwest (2004_Group A), Southwest (2015_Group B), and southeast (2015_Group C), respectively. Blood samples were collected from the study participants for DNA extraction and a nested PCR for P. falciparum identification. Samples that were positive for P. falciparum were genotyped for the pfk13 gene using the Sanger sequencing method. The single nucleotide polymorphisms were analysed using the Bioedit software. Results A total of 116, 125, and 83 samples were positive for P. falciparum, respectively for the samples collected from the Southwest (2004 and 2015) and southeast (2015). Parasite DNA samples collected from febrile children in 2004 (Group A; n = 71) and 2015 (Group B; n = 73) in Osogbo Western Nigeria and 2015_Group C (n = 36) in southeast Nigeria were sequenced successfully. This study did not observe mutations associated with the in vitro resistance in southeast Asia, such as Y493H, R539T, I543T, and C580Y. Two new polymorphisms V520A and V581I were observed in two samples collected in Osogbo, Southwest Nigeria. These two mutations occurred in the year 2004 (Group A) before the introduction of ACT. Six mutations were identified in 17% of the samples collected in southeast Nigeria. One of these mutations (D547G) was non-synonymous, while the remaining (V510V, R515R, Q613Q, E688E, and N458N) were synonymous. Also, one (2%) heterozygote allele was identified at codon 458 in the 2015 (Group C) samples. Conclusions None of the mutations observed in this study were previously validated to be associated with ART resistance. These results, therefore, suggest that artemisinin is likely to remain highly effective in treating malaria in the study areas that are malarious zone.

Comparative Evaluation of the Amount of Sorption and Solubility Seen in Soft Liner with Herbal and Commercially Available Denture Cleanser - An In vitro Study

2021 ◽  
pp. 245-254
Author(s):  
Malika J. Sehgal ◽  
Surekha Dubey
Keyword(s):  
Artificial Saliva ◽  
In Vitro Study ◽  
Acrylic Resin ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Group A ◽  
Soft Liner ◽  
Soft Denture Liner ◽  
Group B

Aims: the aim of the current study is to assess the quantity of sorption and solubility seen in the soft denture liner with herbal (neem) and commercially (clinsodent) available denture cleanser. Materials and Methods: The cross sectional study was carried out in the Department of Prosthodontics at Sharad Pawar Dental College And Hospital between February 2021 and July 2021. 52 samples of heat cured acrylic resin of circular shape were prepared using a stainless steel mould. The resilient liner was applied to all the samples using a denture adhesive. All samples will then be desiccated for 24 hours to get a stable or conditioned weight W1. The samples will then be divided into 2 groups namely: Group A (clinsodent group) and the Group B (herbal denture cleanser group). All the samples were immersed daily in cleanser for 8 hour and then transferred to artificial saliva for rest 16 hours of the day. Solutions of artificial saliva and denture cleanser was changed daily for the entire period of study that is 7 days. Later, all the test samples were removed from saliva, wiped dry, weighed for saturated weight W2. - After desiccating again for 24 hours the samples were again assessed for renovated weight that is W3. Results: With respect to sorption and solubility it was found that the clinsodent group exhibited greater percentage of sorption when compared to the neem denture cleanser group after a period of 7 days, p-values of 0.0001,S. Conclusion: It can be established that the solubility and sorption values of clinsodent group were higher when compared to the herbal denture cleanser group. Overall, neem in the form of denture cleanser performed better than clinsodent.

scholarly journals Occurrence of pfatpase6 Single Nucleotide Polymorphisms Associated with Artemisinin Resistance among Field Isolates of Plasmodium falciparum in North-Eastern Tanzania

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Jaffu Chilongola ◽  
Arnold Ndaro ◽  
Hipolite Tarimo ◽  
Tamara Shedrack ◽  
Sakurani Barthazary ◽  
...  
Keyword(s):  
Artemisinin Resistance ◽  
Dried Blood Spots ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Clear Trend ◽  
Cross Sectional ◽  
Archived Samples ◽  
Current Prevalence ◽  
Transmission Area

We aimed to determine the current prevalence of four P. falciparum candidate artemisinin resistance biomarkers L263E, E431K, A623E, and S769N in the pfatpase6 gene in a high transmission area in Tanzania in a retrospective cross sectional study using 154 archived samples collected from three previous malaria studies in 2010, 2011 and 2013. Mutations in pfatpase6 gene were detected in parasite DNA isolated from Dried Blood Spots by using PCR-RFLP. We observed overall allelic frequencies for L263E, E431K, A623E, and S769N to be 5.8% (9/154), 16.2% (25/154), 0.0% (0/154), and 3.9% (6/154). The L263E mutation was not detected in 2010 but occurred at 3.9% and 2.6% in 2011 and 2013 respectively. The L263E mutation showed a significant change of frequency between 2010 and 2011, but not between 2011 and 2013 P<0.05. Frequency of E431K was highest of all without any clear trend whereas S769N increased from 2.2% in 2010 to 3.6% in 2011 and 5.1% in 2013. A623E mutation was not detected. The worrisome detection and the increase in the frequency of S769N and other mutations calls for urgent assessment of temporal changes of known artemisinin biomarkers in association with in vivo ACT efficacy.

scholarly journals Assessment of antimalarial drug resistant markers in asymptomatic Plasmodium falciparum infections after 4 years of indoor residual spraying in Northern Ghana

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0233478
Author(s):  
James L. Myers-Hansen ◽  
Benjamin Abuaku ◽  
Muyiwa K. Oyebola ◽  
Benedicta A. Mensah ◽  
Collins Ahorlu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Combination Therapy ◽  
Scale Up ◽  
Gene Mutations ◽  
Indoor Residual Spraying ◽  
Northern Ghana ◽  
Drug Resistant ◽  
Nucleotide Polymorphisms ◽  
Control Activity ◽  
Cross Sectional

Background Drug 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. Methods A 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. Results There 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. Conclusion The 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.

scholarly journals Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Afolabi Owoloye ◽  
Michael Olufemi ◽  
Emmanuel T. Idowu ◽  
Kolapo M. Oyebola
Keyword(s):  
Plasmodium Falciparum ◽  
Partial Resistance ◽  
Meta Analysis ◽  
Artemisinin Resistance ◽  
Health Impact ◽  
Nucleotide Polymorphisms ◽  
African Countries ◽  
Effective Interventions ◽  
Resistance Markers

Abstract Background The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance. Methods Findings from published research articles on the prevalence of pfk13, pfcoronin and pfatpase6 polymorphisms in Africa were collated. PubMed, Embase and Google Scholar were searched for relevant articles reporting polymorphisms in these genes across Africa from 2014 to August 2021, for pfk13 and pfcoronin. For pfatpase6, relevant articles between 2003 and August 2021 were retrieved. Results Eighty-seven studies passed the inclusion criteria for this analysis and reported 742 single nucleotide polymorphisms in 37,864 P. falciparum isolates from 29 African countries. Five validated-pfk13 partial resistance markers were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, F446I in Mali, C580Y in Ghana, and P553L in an Angolan isolate. In Tanzania, three (L263E, E431K, S769N) of the four mutations (L263E, E431K, A623E, S769N) in pfatpase6 gene associated with high in vitro IC50 were reported. pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya, and Congo, with P76S being the most prevalent mutation. Conclusions This meta-analysis provides an overview of the prevalence and widespread distribution of pfk13, pfcoronin and pfatpase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria across the continent. Graphical Abstract

scholarly journals Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum

2021 ◽  
Author(s):  
Afolabi Owoloye ◽  
Michael Juwon Olufemi ◽  
Emmanuel Taiwo Idowu ◽  
Kolapo Muyiwa Oyebola
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Mutations ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Health Impact ◽  
Nucleotide Polymorphisms ◽  
African Countries ◽  
Effective Interventions ◽  
Failure Monitoring ◽  
Published Research

Abstract The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapies (ACTs). However, the emergence of artemisinin (ART) resistance in South-East Asia and reports of delayed parasite sensitivity to ACTs in African parasites signal an imminent treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is required to stop resistance in its tracks. Plasmodium falciparum Kelch-13 (Pfk13), Pfcoronin and PfATPase6 gene mutations have been associated with ART resistance. In this review, we collated findings from published research articles to establish the prevalence of Pfk13, Pfcoronin and PfATPase6 polymorphisms in Africa. We searched PubMed, Embase and Google Scholar for relevant articles reporting polymorphisms in these genes across Africa between 2014 to 2021. Seventy-two studies which passed the inclusion criteria reported 739 single nucleotide polymorphisms (331 unique variants) from 34,353 samples collected in 26 African countries. Four validated Pfk13 resistant markers linked with delayed parasite clearance were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, and F446I in Mali, and P553L in Angola. In Tanzania, three (L263E, E431K, and S769N) of the four mutations (L263E, E431K, A623E, and S769N) in PfATPase6 gene previously associated with delayed parasite clearance in presence of artemisinin were reported. Pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya and Congo, with P76S being the most prevalent Pfcoronin mutation. Our findings demonstrate independent emergence and widespread distribution of Pfk13, Pfcoronin and PfATPase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria in Africa.

scholarly journals Stable Artesunate Resistance in A Humanized Mouse Model of Plasmodium falciparum

2021 ◽  
Author(s):  
Sheetal Saini ◽  
Rajinder Kumar ◽  
Rajeev K. Tyagi
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Malaria Infection ◽  
Artemisinin Resistance ◽  
Antimalarial Drugs ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Human Malaria

Plasmodium falciparum, the most devastating human malaria parasite, confers higher morbidity and mortality. Although efforts have been made to develop an effective malaria vaccine, stage- and species-specific short-lived immunity crippled these efforts. Hence, antimalarial drug treatment becomes a mainstay for the treatment of malaria infection in the wake of the unavailability of an effective vaccine. Further, there has been a wide array of antimalarial drugs effective against various developmental stages of P. falciparum due to their different structures, modes of action, and pharmacodynamics as well as pharmacokinetics. The development of resistance against almost all frontline drugs by P. falciparum indicates the need for combination therapy (artemisinin-based combination therapy; ACT) to treat patients with P. falciparum. A higher pool of parasitemia under discontinuous in vivo artemisinin drug pressure in a developed humanized mouse allows the selection of artesunate resistant (ART-R) P. falciparum. Intravenously administered artesunate, using either single flash doses or a 2-day regimen, to the P. falciparum-infected human blood chimeric NOD/SCID.IL-2Rγ−/− immunocompromised (NSG) mice, with progressive dose increments upon parasite recovery, was the strategy deployed to select resistant parasites. Parasite susceptibility to artemisinins and other antimalarial compounds was characterized in vitro and in vivo. P. falciparum has shown to evolve extreme artemisinin resistance as well as co-resistance to antimalarial drugs. Overall, the present information shall be very useful in devising newer therapeutic strategies to treat human malaria infection.

scholarly journals Thyroid Peroxidase Gene Mutation in Patients with Congenital Hypothyroidism in Isfahan, Iran

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Mahin Hashemipour ◽  
Fahimeh Soheilipour ◽  
Sakineh Karimizare ◽  
Hossein Khanahmad ◽  
Morteza Karimipour ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Gene Mutations ◽  
Cross Sectional Study ◽  
Thyroid Peroxidase ◽  
Nucleotide Polymorphisms ◽  
Salting Out ◽  
Cross Sectional ◽  
Peroxidase Gene ◽  
Thyroid Dyshormonogenesis ◽  
Unknown Gene

Background. Thyroid peroxidase gene (TPO) mutations are one of the most common causes of thyroid dyshormonogenesis in patients with congenital hypothyroidism (CH). In this study, the prevalence of TPO gene mutations in patients with thyroid dyshormonogenesis in Isfahan was investigated.Methods. In this cross-sectional study, genomic DNA of 41 patients with permanent CH due to thyroid dyshormonogenesis was extracted using the salting out method. The 17 exonic regions of the TPO gene were amplified. SSCP technique was performed for scanning of the exonic regions of the TPO gene, except exon 8. DNA sequencing was performed for those with different migration patterns in SSCP by chain termination method. Exon 8 was sequenced directly in all patients. In 4 patients, all fragments were also sequenced.Results. One missense mutationc.2669G>A(NM_000547.5) at exon 15 (14th coding exon) in one patient in homozygous form and seven different single nucleotide polymorphisms (SNPs) in exons 1, 7, 8, 11, and 15 of TPO gene.Conclusion. The TPO gene mutations among CH patients with dyshormonogenesis in Isfahan were less frequent in comparison with other similar studies. It may be due to the presence of other unknown gene mutations which could not be detected by SSCP and sequencing methods.

scholarly journals The Pandemic and Changes in the Self-Perception of Teacher Digital Competences of Infant Grade Students: A Cross Sectional Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4756
Author(s):  
Rosalía Romero-Tena ◽  
Carmen Llorente-Cejudo ◽  
María Puig-Gutiérrez ◽  
Raquel Barragán-Sánchez
Keyword(s):  
Intervention Group ◽  
Cross Sectional Study ◽  
Self Perception ◽  
Digital Competence ◽  
Cross Sectional ◽  
Self Perceptions ◽  
Group A ◽  
Different Dimensions ◽  
The Difference ◽  
Group B

Without having a reaction time, the pandemic has caused an unprecedented transformation in universities around the world, leading to a revolution from structured models anchored in the conception of transmission of training towards a teaching approach-learning saved thanks to the incorporation of technology. This study aims to verify whether the pandemic situation has influenced the digital competence self-perception of students. Comparing two groups during the academic years 2019/2020 and 2020/2021, the instrument used is the questionnaire for digital competence “DigCompEdu Check-In” for future teachers. After the educational intervention, group A (before COVID-19) presented higher self-perceptions of competence than group B (during COVID-19); the pandemic situation caused by COVID-19 has negatively influenced students’ self-perception of their digital skills in the pretest in the different dimensions under study. Before receiving the training, the group that did not experience the pandemic enjoyed a higher self-perception of their competencies than the group that experienced the pandemic. The data obtained indicate that the difference exists, and that it is statistically significant, and may be a consequence of the clear relationship between self-perception and the way in which students face reality through their personal and subjective vision.

scholarly journals Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

2021 ◽  
Vol 18 (12) ◽  
pp. 6597
Author(s):  
Gloria Pérez-Rubio ◽  
Luis Alberto López-Flores ◽  
Ana Paula Cupertino ◽  
Francisco Cartujano-Barrera ◽  
Luz Myriam Reynales-Shigematsu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Quitting Smoking ◽  
Genes Encoding ◽  
Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

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