scholarly journals Prevalence of Plasmodium falciparum Chloroquine Resistance Transporter (Pfcrt76T) Mutation Associated with Antimalarial Drug Resistance in Two Different Epidemiological Setting (Banfora and Saponé) in Burkina Faso Few Years after the Implementation of Artemisnine Based Combination Therapy (ACTs)

2020 ◽  
pp. 1-11
Author(s):  
Séni Nikiema ◽  
Samuel Sindié Sermé ◽  
Salif Sombié ◽  
Amidou Diarra ◽  
Noelie Bere Henry ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Public Health Problem ◽  
Antimalarial Drugs ◽  
Sub Saharan Africa ◽  
Chloroquine Resistance ◽  
Chloroquine Resistance Transporter ◽  
Significant Difference ◽  
Sub Saharan ◽  
Biology Laboratory

Introduction: In spite of considerable progress, malaria remains a public health problem in many areas, particularly in sub-Saharan Africa. One major complexity of malaria disease is caused by the development and the spread of vector and parasite resistance to insecticides and antimalarial drugs respectively. The Pfcrt76T gene mutation has been validated as a marker conferring resistance to chloroquine and other antimalarial drugs. The extension of Plasmodium falciparum resistance to commonly used antimalarial drugs (chloroquine, sulfadoxine-pyrimethamine) led to the adoption and the use of artemisinin-based combinations in Burkina Faso since 2005. Aims: The present study was initiated to assess the prevalence of the Pfcrt76T mutation in two different malaria epidemiological setting after a decade of introduction of artemisinin-based combination therapies (ACTs) in Burkina Faso.  Methodology:  The study population consisted of 181 uncomplicated malaria patients recruited in Banfora and Saponé health districts in 2012 and 2013. Blood samples were collected from finger prick on filter paper, dried and sent to the Molecular Biology Laboratory at Centre National de Recherche et de Formation sur le Paludisme (CNRFP) for molecular analyzes. DNA of Plasmodium falciparum was extracted with DNA extraction kit (Qiagen®) and the Pfcrt76T mutation was determined based on Polymerase Chain Reaction / Restriction Fragment Length Polymorphism technique (RFLP). Results:  The results of this study showed that the frequency of the pfcrt76T mutant allele (33.7%) was statistically lower than the Pfcrt76K wild-type allele (57.4%) in the study area. Moreover, the prevalence of Pfcrt76T mutation was neither associated with the patient age nor with the parasite density while a significant difference was observed between the two epidemiological setting, Banfora and Saponé. Conclusion: The findings of this study has shown a drop in the prevalence of mutant parasites Pfcrt76T in both the study area eight years after the introduction of ACTs compared to previous studies.

scholarly journals Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana

2018 ◽  
Vol 1 ◽  
pp. 1 ◽  
Author(s):  
James Abugri ◽  
Felix Ansah ◽  
Kwaku P. Asante ◽  
Comfort N. Opoku ◽  
Lucas A. Amenga-Etego ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Chloroquine Resistance ◽  
Published Data ◽  
Nucleotide Polymorphisms ◽  
Triple Mutant ◽  
Chloroquine Resistance Transporter ◽  
Significant Difference ◽  
Quadruple Mutant ◽  
Study Sites

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) and the antifolate drug sulfadoxine-pyrimethamine (SP) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we genotyped single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter (pfcrt, PF3D7_0709000), multidrug resistance (pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase (pfdhfr, PF3D7_0417200) and dihydropteroate synthase (pfdhps, PF3D7_0810800) genes in children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) between 2012 and 2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10% and 65% of infections respectively. Most of the isolates harboured the antifolate resistance-associated pfdhfr 51I, 59R and 108N alleles, including 68% of them with the triple mutant pfdhfr I51R59N108 combination. Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G, which was more common in Accra than at the other sites. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination (I51R59N108/G437). Conclusion: Comparison of the present results to previously published data shows a significant decrease in the prevalence of CQ resistance alleles during the 12 years after CQ withdrawal, but an increase in the alleles that mediate SP resistance, which could be due to the continuous use of antifolate drugs for prophylaxis.

scholarly journals Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana

2018 ◽  
Vol 1 ◽  
pp. 1
Author(s):  
James Abugri ◽  
Felix Ansah ◽  
Kwaku P. Asante ◽  
Comfort N. Opoku ◽  
Lucas A. Amenga-Etego ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Chloroquine Resistance ◽  
Nucleotide Polymorphisms ◽  
Chloroquine Resistance Transporter ◽  
Significant Difference ◽  
Quadruple Mutant ◽  
Study Sites

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Sulphadoxine-pyrimethamine (SP) which was the second line antimalarial drug in Ghana, was now adopted for intermittent preventive treatment of malaria in pregnancy (IPTp). Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we employed restriction fragment length polymorphism polymerase chain reaction to genotype and compare single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter ( pfcrt, PF3D7_0709000), multidrug resistance ( pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase ( pfdhfr, PF3D7_0417200) and dihydropteroate synthase ( pfdhps, PF3D7_0810800) genes. Parasites were collected from children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) in 2012-2013 and 2016-2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10.2% and 65.1% of infections, respectively. The majority of the isolates harboured the antifolate resistance-associated pfdhfr alleles 51I (83.4%), 59R (85.9 %) and 108N (90.5%). Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G, which was more common in Accra compared to Kintampo for the 2016-2017 isolates. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination (I 51 R 59 N 108/ G 437). CQ resistance alleles decreased during the 12 years after CQ withdrawal, but an mediate SP resistance alleles increased. Conclusion: Surveillance of the prevalence of resistance alleles is necessary in monitoring the efficacy of antimalarial drugs.

scholarly journals Genomic Analysis of Plasmodium vivax in Southern Ethiopia Reveals Selective Pressures in Multiple Parasite Mechanisms

2019 ◽  
Vol 220 (11) ◽  
pp. 1738-1749 ◽  
Author(s):  
Sarah Auburn ◽  
Sisay Getachew ◽  
Richard D Pearson ◽  
Roberto Amato ◽  
Olivo Miotto ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Regulation Of Gene Expression ◽  
Genomic Analysis ◽  
Sub Saharan Africa ◽  
Chloroquine Resistance ◽  
Southern Ethiopia ◽  
Chloroquine Resistance Transporter ◽  
Negative Trait ◽  
Sub Saharan ◽  
Duffy Negative

Abstract The Horn of Africa harbors the largest reservoir of Plasmodium vivax in the continent. Most of sub-Saharan Africa has remained relatively vivax-free due to a high prevalence of the human Duffy-negative trait, but the emergence of strains able to invade Duffy-negative reticulocytes poses a major public health threat. We undertook the first population genomic investigation of P. vivax from the region, comparing the genomes of 24 Ethiopian isolates against data from Southeast Asia to identify important local adaptions. The prevalence of the Duffy binding protein amplification in Ethiopia was 79%, potentially reflecting adaptation to Duffy negativity. There was also evidence of selection in a region upstream of the chloroquine resistance transporter, a putative chloroquine-resistance determinant. Strong signals of selection were observed in genes involved in immune evasion and regulation of gene expression, highlighting the need for a multifaceted intervention approach to combat P. vivax in the region.

scholarly journals Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: a randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Gilles Ndayisaba ◽  
Adoke Yeka ◽  
Kwaku Poku Asante ◽  
Martin P. Grobusch ◽  
Etienne Karita ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Adverse Events ◽  
Falciparum Malaria ◽  
Phase Ii ◽  
Dose Escalation ◽  
Sub Saharan Africa ◽  
Uncomplicated Falciparum Malaria ◽  
Wide Range ◽  
Significant Difference ◽  
Sub Saharan

Abstract Background The novel anti-malarial cipargamin (KAE609) has potent, rapid activity against Plasmodium falciparum. Transient asymptomatic liver function test elevations were previously observed in cipargamin-treated subjects in two trials: one in malaria patients in Asia and one in volunteers with experimentally induced malaria. In this study, the hepatic safety of cipargamin given as single doses of 10 to 150 mg and 10 to 50 mg once daily for 3 days was assessed. Efficacy results, frequency of treatment-emerging mutations in the atp4 gene and pharmacokinetics have been published elsewhere. Further, the R561H mutation in the k13 gene, which confers artemisinin-resistance, was associated with delayed parasite clearance following treatment with artemether–lumefantrine in Rwanda in this study. This was also the first study with cipargamin to be conducted in patients in sub-Saharan Africa. Methods This was a Phase II, multicentre, randomized, open-label, dose-escalation trial in adults with uncomplicated falciparum malaria in five sub-Saharan countries, using artemether–lumefantrine as control. The primary endpoint was ≥ 2 Common Terminology Criteria for Adverse Events (CTCAE) Grade increase from baseline in alanine aminotransferase (ALT) or aspartate transaminase (AST) during the 4-week trial. Results Overall, 2/135 patients treated with cipargamin had ≥ 2 CTCAE Grade increases from baseline in ALT or AST compared to 2/51 artemether–lumefantrine patients, with no significant difference between any cipargamin treatment group and the control group. Cipargamin exposure was comparable to or higher than those in previous studies. Hepatic adverse events and general safety and tolerability were similar for all cipargamin doses and artemether–lumefantrine. Cipargamin was well tolerated with no safety concerns. Conclusions This active-controlled, dose escalation study was a detailed assessment of the hepatic safety of cipargamin, across a wide range of doses, in patients with uncomplicated falciparum malaria. Comparison with previous cipargamin trials requires caution as no clear conclusion can be drawn as to whether hepatic safety and potential immunity to malaria would differ with ethnicity, patient age and or geography. Previous concerns regarding hepatic safety may have been confounded by factors including malaria itself, whether natural or experimental infection, and should not limit the further development of cipargamin. Trial registration ClinicalTrials.gov number: NCT03334747 (7 Nov 2017), other study ID CKAE609A2202

scholarly journals Unravelling the Perspectives of Day and Night Traders in Selected Markets within a Sub-Saharan African City with a Malaria Knowledge, Attitude and Practice Survey

2021 ◽  
Vol 18 (7) ◽  
pp. 3468
Author(s):  
Patience B. Tetteh-Quarcoo ◽  
Nicholas T. K. D. Dayie ◽  
Kevin Kofi Adutwum-Ofosu ◽  
John Ahenkorah ◽  
Emmanuel Afutu ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Malaria Treatment ◽  
Sub Saharan Africa ◽  
African City ◽  
Cross Sectional ◽  
Attitudes And Practices ◽  
Treatment Type ◽  
Significant Difference ◽  
High Knowledge ◽  
Sub Saharan

Background: Malaria is still endemic in sub-Saharan Africa, with a high disease burden. Misconceptions about malaria contribute to poor attitudes and practices, further increasing the burden in endemic countries. Studies have examined the knowledge, attitudes, and practices (KAP) of malaria among different populations. However, there seems to be no available literature reporting on the perspectives of day and night market traders. To the best of our knowledge, this is the first report on malaria KAP with a focus on day and night market traders. Methods: A descriptive cross-sectional study involving day and night market traders in 10 selected markets within the Greater Accra Region of Ghana was carried out. Data were collected from consenting respondents using a structured questionnaire. Results: Of the 760 respondents (33.3% (n = 253) night and 66.7% (n = 507) day traders) interviewed, there was no significant difference between the day and night market traders in terms of malaria KAP. Although the market traders had an overall moderate knowledge (54.0% of the day traders and 56.5% of the night traders), misconceptions about malaria (especially that it could be caused by exposure to the sun) still existed among the traders. Moreover, the majority of the traders who demonstrated high knowledge (43.98%, n = 250) did not always take laboratory tests to confirm their suspicion, indicating poor attitude. Furthermore, the market traders’ choice of drug for malaria treatment (p = 0.001) and preferred malaria treatment type (orthodox or herbal) (p = 0.005) were significantly associated with their knowledge level. Conclusions: Despite the observation that no significant difference in KAP exists between day and night market traders, appropriate health education programs and interventions still need to be directed at misconceptions, poor attitudes, and poor practices revealed by this study. This will ultimately help in the prevention and control of malaria in Ghana, and globally.

scholarly journals Control trial of porcine cysticercosis in Uganda using a combination of the TSOL18 vaccination and oxfendazole

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Zachary Nsadha ◽  
Chris Rutebarika ◽  
Chrisostom Ayebazibwe ◽  
Bukenya Aloys ◽  
M. Mwanja ◽  
...  
Keyword(s):  
Taenia Solium ◽  
Control Program ◽  
Control Area ◽  
Sub Saharan Africa ◽  
Intermediate Hosts ◽  
Porcine Cysticercosis ◽  
Intervention Area ◽  
Significant Difference ◽  
Sub Saharan ◽  
Village Communities

Abstract Background Neurocysticercosis caused by Taenia solium when the parasite lodges in the central nervous system, is an important cause of human seizures and mortality in sub-Saharan Africa. The parasite is prevalent in many regions of Uganda. Pigs are intermediate hosts for T. solium, and we evaluated a T. solium control program in pigs, involving vaccination of pigs with the TSOL18 vaccine and treatment with oxfendazole. Methods The study was conducted in two districts of Eastern Uganda involving the rural village communities of Bukedea (intervention area) and Kumi (control area) during 2016–2017. Seven hundred and thirty-four households were enrolled in the study. Pigs in the intervention area received intramuscular immunizations with TSOL18 (Cysvax™) and an oral medication with 30 mg/kg oxfendazole (Paranthic™) at approximately 3-monthly intervals for 18 months. Porcine cysticercosis was evaluated by post-mortem examination. At the beginning of the study, 111 pigs were examined. In an interim evaluation in the intervention area, 55 pigs were evaluated 12 months after starting the project. At the end of the study approximately 3 months after the final intervention, 55 pigs from the intervention area and 56 pigs from the control area were evaluated. Results The prevalence of porcine cysticercosis for the two sites was 16.2% at the beginning of the study (17.2% in the intervention area and 15.1% in the control area) with no statistically significant difference (P = 0.759) between the two study sites. Among the 110 animals assessed from the intervention site (55 at the interim evaluation and 55 at the final evaluation), no pig with viable T. solium cysts was found. There was a statistically significant difference between the prevalence at baseline (17.2%) and at the end of the study (0%) in the intervention area (P = 0.001) and a statistically significant difference between the intervention (0%) and control areas (5.4%) (P = 0.041) at the end of the study. Conclusions Three-monthly concurrent vaccination of pigs with the TSOL18 vaccine and medication with oxfendazole eliminated T. solium transmission by the animals involved in the study. Application of vaccination with medication in pigs has the potential to reduce transmission of T. solium in Uganda and other endemic countries.

scholarly journals The impact of HIV-associated immunosuppression on the Plasmodium falciparum chloroquine resistance transporter gene (PfCRT) of HIV patients in Akure, Nigeria

2020 ◽  
Vol 44 (1) ◽  
Author(s):  
Iyabo Adepeju Simon-Oke ◽  
Adeola Olanireti Ade-Alao ◽  
Foluso Ologundudu
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Prevalence ◽  
Cd4 Count ◽  
Chloroquine Resistance ◽  
Hiv Care ◽  
Transporter Gene ◽  
Hiv Patients ◽  
Chloroquine Resistance Transporter ◽  
Hiv Test ◽  
Low Prevalence

Abstract Background The study evaluated the prevalence of malaria and Plasmodium falciparum chloroquine resistance transporter gene (PfCRT) in HIV patients attending Specialist Hospital, Akure. This study was carried out between April and June 2019. Three hundred and seventeen (317) patients attending the antiretroviral clinic (ART) were involved, out of which 89 (28.08%) were males and 228 (71.92%) were females. HIV test was done using the Unigold® HIV test kit, malaria test was done using thick and thin blood smear, CD4 test was done using the Partec® CD4 counter and PCR was used to detect the presence of plasmodium falciparum mutant gene. The data obtained from this analysis was subjected to Pearson’s Chi-square test. Results The overall result showed low prevalence of malaria (23.03%) in the sampled patients. Highest malaria prevalence (31.0%) was recorded in HIV patients with CD4 count between 200–500 cells/μl of blood, with the males recording 24.7% malaria prevalence. The age group 20–29 years recorded the highest prevalence of 27.3%. A higher prevalence 91.1% of PfCRT gene in HIV-positive and (40.0%) in HIV-negative patients was recorded with 100% prevalence in patients with CD4 count ≤ 200. This shows that the low prevalence of malaria recorded in this study could be credited to good health-seeking attitude of HIV patients and the upscale of HIV care and treatment centres. Conclusion The high prevalence of PfCRT gene shows that treatment of malaria with chloroquine is still being practised despite the availability of artemisinin-based combination therapy (ACTs) as the recommended regimen for malaria treatment.

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