scholarly journals Assessment of Plasmodium falciparum anti-malarial drug resistance markers in pfcrt and pfmdr1 genes in isolates from Honduras and Nicaragua, 2018–2021

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Gustavo Fontecha ◽  
Alejandra Pinto ◽  
Osman Archaga ◽  
Sergio Betancourth ◽  
Lenin Escober ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Central America ◽  
Gene Fragment ◽  
Genetic Approach ◽  
First Line ◽  
Blood Samples ◽  
Resistance Markers ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
Line Drug

Abstract Background Central America and the island of Hispaniola have set out to eliminate malaria by 2030. However, since 2014 a notable upturn in the number of cases has been reported in the Mosquitia region shared by Nicaragua and Honduras. In addition, the proportion of Plasmodium falciparum malaria cases has increased significantly relative to vivax malaria. Chloroquine continues to be the first-line drug to treat uncomplicated malaria in the region. The objective of this study was to evaluate the emergence of chloroquine resistant strains of P. falciparum using a genetic approach. Plasmodium vivax populations are not analysed in this study. Methods 205 blood samples from patients infected with P. falciparum between 2018 and 2021 were analysed. The pfcrt gene fragment encompassing codons 72–76 was analysed. Likewise, three fragments of the pfmdr1 gene were analysed in 51 samples by nested PCR and sequencing. Results All samples revealed the CVMNK wild phenotype for the pfcrt gene and the N86, Y184F, S1034C, N1042D, D1246 phenotype for the pfmdr1 gene. Conclusions The increase in falciparum malaria cases in Nicaragua and Honduras cannot be attributed to the emergence of chloroquine-resistant mutants. Other possibilities should be investigated further. This is the first study to report the genotype of pfmdr1 for five loci of interest in Central America.

Assessment of Plasmodium Falciparum Antimalarial Drug Resistance Markers in pfcrt and pfmdr1 Genes in Isolates from Honduras and Nicaragua, 2018-2021

2021 ◽  
Author(s):  
Gustavo Adolfo Fontecha ◽  
Alejandra Pinto ◽  
Osman Archaga ◽  
Sergio Betancourth ◽  
Lenin Escober ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Central America ◽  
Gene Fragment ◽  
Genetic Approach ◽  
First Line ◽  
Antimalarial Drug Resistance ◽  
Resistance Markers ◽  
Resistant Strains ◽  
Resistant Mutants ◽  
Line Drug

Abstract Background: Central America and the island of Hispaniola have set out to eliminate malaria by 2030. However, since 2014 a notable upturn in the number of cases has been reported in La Mosquitia region shared by Nicaragua and Honduras. In addition, the proportion of Plasmodium falciparum malaria cases has increased significantly relative to vivax malaria. Chloroquine continues to be the first line drug to treat uncomplicated malaria in the region. The objective of this study was to evaluate the emergence of chloroquine resistant strains using a genetic approach. Methods: 205 blood samples from patients infected with P. falciparum between 2018 and 2021 were analyzed. The pfcrt gene fragment encompassing codons 72-76 was analyzed. Likewise, three fragments of the pfmdr1 gene were analyzed in 51 samples by nested PCR and sequencing. Results: All samples revealed the CVMNK wild phenotype for the pfcrt gene and the N86, Y184F, S1034C, N1042D, D1246 phenotype for the pfmdr1 gene. Conclusions: The increase in falciparum malaria cases in Nicaragua and Honduras cannot be attributed to the emergence of chloroquine-resistant mutants. Other possibilities should be investigated further. This is the first study to report the genotype of pfmdr1 for five loci of interest in Central America.

scholarly journals In Vitro Monitoring of Plasmodium falciparum Drug Resistance in French Guiana: a Synopsis of Continuous Assessment from 1994 to 2005

2007 ◽  
Vol 52 (1) ◽  
pp. 288-298 ◽  
Author(s):  
Eric Legrand ◽  
Béatrice Volney ◽  
Jean-Baptiste Meynard ◽  
Odile Mercereau-Puijalon ◽  
Philippe Esterre
Keyword(s):  
Plasmodium Falciparum ◽  
French Guiana ◽  
Control Program ◽  
Drug Susceptibility ◽  
Warning Signs ◽  
Strongly Correlated ◽  
First Line ◽  
Drug Pressure ◽  
Line Drug

ABSTRACT Implemented as one arm of the malaria control program in French Guiana in the early 1990s, our laboratory has since established in vitro profiles for parasite drug susceptibility to a panel of eight antimalarials for more than 1,000 Plasmodium falciparum isolates from infected patients. The quinine-doxycycline combination was introduced in 1995 as the first-line drug treatment against uncomplicated P. falciparum malaria, replacing chloroquine, and the first-line drug combination was changed to the artemether-lumefantrine combination in 2002. Resistance to chloroquine declined 5 years after it was dropped in 1995 as the first-line drug, but unlike similar situations in Africa, there was a rapid halt to this decline. Doxycycline susceptibility substantially decreased from 2002 to 2005, suggesting parasite selection under quinine-doxycycline drug pressure. Susceptibility to mefloquine decreased from 1997 onward. Throughout the period from 1994 to 2005, most isolates were sensitive in vitro to quinine, amodiaquine, and atovaquone. Susceptibility to amodiaquine was strongly correlated with that to chloroquine and to a lesser extent with that to mefloquine and halofantrine. Susceptibilities to mefloquine and to halofantrine were also strongly correlated. There were two alerts issued for in vitro artemether resistance in the period from 2002 to 2003 and again in 2005, both of which could be associated with the presence of an S769N polymorphism in the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)-type P. falciparum ATPase6 (PfATPase6) gene. Analysis of susceptibility to lumefantrine, conducted for the first time in 2005, indicates an alarming rate of elevated 50% inhibitory concentrations. In vitro monitoring of parasite drug susceptibility should be pursued to further document the consequences of specific drug policies on the local parasite population and, in particular, to establish profiles of susceptibility to individual components of drug combinations to provide early warning signs of emerging parasite resistance.

An overview of some drugs: Lopinavir, Ritonavir, Chloroquine, Hydroxy chloroquine and Interferon as a effective treatment against COVID-19

2020 ◽  
Vol 10 (1) ◽  
pp. 20-24
Author(s):  
Sujaritha J ◽  
Deepa sankar N ◽  
Mathivathani K ◽  
Aravindh G ◽  
Gnanasekaran G
Keyword(s):  
Rheumatoid Arthritis ◽  
Plasmodium Falciparum ◽  
Drug Therapy ◽  
Hiv Infection ◽  
Effective Treatment ◽  
Protease Inhibitors ◽  
First Line ◽  
Duration Of Illness ◽  
Line Drug

Lopinavir, Ritonovir and Interferon (IFN) are anti-viral drugs mainly used in the treatment of HIV infection by protease inhibitors. Chloroquine and Hydroxychloroquine are used in the treatment of malarial causing infection such as Plasmodium falciparum and also auto immune condition such as rheumatoid arthritis. Chloroquine makes toxic for the parasite to digest its host hemoglobin and disrupting the virus ability to enter the cell. The anti-viral and anti-malarial drugs are used in the first line drug therapy for the treatment of COVID-19. The aim of this therapy is to minimize the symptoms and shortens the duration of illness.

scholarly journals Prevalence of Fluoroquinolone Resistance among Tuberculosis Patients in Shanghai, China

2009 ◽  
Vol 53 (7) ◽  
pp. 3170-3172 ◽  
Author(s):  
Peng Xu ◽  
Xia Li ◽  
Ming Zhao ◽  
Xiaohong Gui ◽  
Kathryn DeRiemer ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Marker ◽  
Pulmonary Tuberculosis ◽  
Multidrug Resistant ◽  
Tuberculosis Treatment ◽  
Fluoroquinolone Resistance ◽  
First Line ◽  
Tuberculosis Patients ◽  
Resistant Strains ◽  
Line Drug

ABSTRACT We determined the prevalence of fluoroquinolone resistance among the isolates of Mycobacterium tuberculosis from 605 pulmonary tuberculosis patients in Shanghai, China. Mutations in gyrA were found in 81.5% of phenotypically fluoroquinolone-resistant isolates and were used as a molecular marker of fluoroquinolone resistance. gyrA mutations were detected in 1.9% of strains pan-susceptible to first-line drugs and 25.1% of multidrug-resistant strains. Fluoroquinolone resistance was independently associated with resistance to at least one first-line drug and prior tuberculosis treatment.

scholarly journals Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade of its use in Kenya

2020 ◽  
Author(s):  
Gabriel M. Kishoyian ◽  
Eliud N. M. Njagi ◽  
George O. Orinda ◽  
Francis T. Kimani ◽  
Kevin Thiongo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Uncomplicated Malaria ◽  
Standard Dose ◽  
Parasite Clearance ◽  
First Line ◽  
Study Population ◽  
Treatment Responses ◽  
Lost To Follow Up ◽  
Line Drug

Abstract Background: Plasmodium falciparum resistance to antimalarial drugs remains to be a major threat to the control of malaria globally. After the deployment of artemisinin-based combination therapy (ACT), there have been reports of reduced sensitivity of the drug to parasite clearance. In Kenya, artemisinin-lumefantrine (AL) is the recommended first-line drug in the treatment of uncomplicated malaria. This study sought to assess the efficacy of AL after its reintroduction in Kenya, a decade later. In this study, we assessed clinical and parasitological responses of children under five years in May and November 2015 in Chulaimbo sub-County, Kisumu, Kenya.Method: Patients of ≥6 and ≤60 months of age with confirmed Plasmodium falciparum mono-infection were enrolled in the study. The patients were treated with a standard dose of AL and followed up for 28 days. During which period we monitored treatment responses and follow-up adherence.Results: Of the 90 patients enrolled, fourteen (14) were lost to follow-up, with 76 completing the study period. Seventy-five patients 75 (98.7%) cleared, parasitemia within 48 hours while one (1.3%) cleared on day 3. There was 100% clinical and parasitological parasite clearance. Conclusion: Artemisinin lumefantrine was found to be highly efficacious to plasmodium falciparum parasites in children aged ≥6 and ≤60 months. Based on this, the drug can be used to treat uncomplicated malaria in the study population. However, there is need for continued monitoring of its effectiveness in children and adults to counter the threat of resistance.

scholarly journals Efficacy of Artemisinin-lumefantrine for the treatment of uncomplicated malaria after more than a decade after its use in Kenya

2020 ◽  
Author(s):  
gabriel m kishoyian ◽  
Eliud N.M. Njagi ◽  
George O. Orinda ◽  
Francis T. Kimani ◽  
Kevin Thiongo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Uncomplicated Malaria ◽  
Standard Dose ◽  
Parasite Clearance ◽  
Close Monitoring ◽  
First Line ◽  
Study Population ◽  
Lost To Follow Up ◽  
Line Drug

Abstract Background: Plasmodium falciparum resistance to antimalarial drugs remains to be a major threat to the control of the disease globally. After the deployment of artemisinin-based combination therapy (ACT), there have been reports of reduced sensitivity of the drug to parasite clearance. In Kenya, artemisinin-lumefantrine (AL) is the recommended first-line drug in the treatment of uncomplicated malaria. This study sought to assess the efficacy of AL after its reintroduction in Kenya, a decade later. We assessed clinical and parasitological responses of children under five years in May and November 2015 in Chulaimbo sub-County, Kisumu, Kenya. Method: Patients of ≥6 and ≤60 months of age with confirmed Plasmodium falciparum mono-infection were enrolled in the study. The children were inpatient for close monitoring, they were treated with a standard dose of AL under supervision of a qualified nurse and followed up for 28 days. We monitored treatment adherence and responses. Efficacy of artemether lumefantrine on Plasmodium falciparum was determined.Results: Of the 90 patients enrolled, fourteen (14) were lost to follow-up, with 76 completing the study period. Seventy-five patients 75 (98.7%) cleared the parasitemia within 48 hours while one (1.3%) cleared on day 3. There was 100% clinical and parasitological parasite clearance. Conclusion: Artemisinin lumefantrine was found to be highly efficacious to plasmodium falciparum parasites in children aged ≥6 and ≤60 months. The results reported here indicate that the drug can be used to treat uncomplicated malaria in the study population. However, there is need for continued monitoring of its effectiveness in children and adults to counter the threat of resistance.

scholarly journals Analytical validation of a real-time hydrolysis probe PCR assay for quantifying Plasmodium falciparum parasites in experimentally infected human adults

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Claire Y. T. Wang ◽  
Emma L. Ballard ◽  
Zuleima Pava ◽  
Louise Marquart ◽  
Jane Gaydon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Plasmodium Falciparum ◽  
18S Rrna ◽  
Drug Efficacy ◽  
18S Rrna Gene ◽  
Molecular Techniques ◽  
Qpcr Assay ◽  
Rrna Gene ◽  
Analytical Sensitivity ◽  
Blood Samples

Abstract Background Volunteer infection studies have become a standard model for evaluating drug efficacy against Plasmodium infections. Molecular techniques such as qPCR are used in these studies due to their ability to provide robust and accurate estimates of parasitaemia at increased sensitivity compared to microscopy. The validity and reliability of assays need to be ensured when used to evaluate the efficacy of candidate drugs in clinical trials. Methods A previously described 18S rRNA gene qPCR assay for quantifying Plasmodium falciparum in blood samples was evaluated. Assay performance characteristics including analytical sensitivity, reportable range, precision, accuracy and specificity were assessed using experimental data and data compiled from phase 1 volunteer infection studies conducted between 2013 and 2019. Guidelines for validation of laboratory-developed molecular assays were followed. Results The reportable range was 1.50 to 6.50 log10 parasites/mL with a limit of detection of 2.045 log10 parasites/mL of whole blood based on a parasite diluted standard series over this range. The assay was highly reproducible with minimal intra-assay (SD = 0.456 quantification cycle (Cq) units [0.137 log10 parasites/mL] over 21 replicates) and inter-assay (SD = 0.604 Cq units [0.182 log10 parasites/mL] over 786 qPCR runs) variability. Through an external quality assurance program, the QIMR assay was shown to generate accurate results (quantitative bias + 0.019 log10 parasites/mL against nominal values). Specificity was 100% after assessing 164 parasite-free human blood samples. Conclusions The 18S rRNA gene qPCR assay is specific and highly reproducible and can provide reliable and accurate parasite quantification. The assay is considered fit for use in evaluating drug efficacy in malaria clinical trials.

scholarly journals New InhA Inhibitors Based on Expanded Triclosan and Di-Triclosan Analogues to Develop a New Treatment for Tuberculosis

2021 ◽  
Vol 14 (4) ◽  
pp. 361
Author(s):  
Sarentha Chetty ◽  
Tom Armstrong ◽  
Shalu Sharma Kharkwal ◽  
William C. Drewe ◽  
Cristina I. De Matteis ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Protein Crystal ◽  
First Line ◽  
Isoniazid Resistance ◽  
Structure Based Drug Design ◽  
Extensively Drug Resistant ◽  
New Treatment ◽  
Flexible Ligands ◽  
Line Drug

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has reinforced the need for the development of new anti-TB drugs. The first line drug isoniazid inhibits InhA. This is a prodrug requiring activation by the enzyme KatG. Mutations in KatG have largely contributed to clinical isoniazid resistance. We aimed to design new ‘direct’ InhA inhibitors that obviate the need for activation by KatG, circumventing pre-existing resistance. In silico molecular modelling was used as part of a rational structure-based drug-design approach involving inspection of protein crystal structures of InhA:inhibitor complexes, including the broad spectrum antibiotic triclosan (TCS). One crystal structure exhibited the unusual presence of two triclosan molecules within the Mycobacterium tuberculosis InhA binding site. This became the basis of a strategy for the synthesis of novel inhibitors. A series of new, flexible ligands were designed and synthesised, expanding on the triclosan structure. Low Minimum Inhibitory Concentrations (MICs) were obtained for benzylphenyl compounds (12, 43 and 44) and di-triclosan derivative (39), against Mycobacterium bovis BCG although these may also be inhibiting other enzymes. The ether linked di-triclosan derivative (38) displayed excellent in vitro isolated enzyme inhibition results comparable with triclosan, but at a higher MIC (125 µg mL−1). These compounds offer good opportunities as leads for further optimisation.

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