scholarly journals Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali

2021 ◽  
Vol 22 (11) ◽  
pp. 6057
Author(s):  
Hamma Maiga ◽  
Anastasia Grivoyannis ◽  
Issaka Sagara ◽  
Karim Traore ◽  
Oumar B. Traore ◽  
...  

Background: Artemether-lumefantrine is a highly effective artemisinin-based combination therapy that was adopted in Mali as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study was designed to measure the efficacy of artemether-lumefantrine and to assess the selection of the P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multi-drug resistance 1 (pfmdr1) genotypes that have been associated with drug resistance. Methods: A 28-day follow-up efficacy trial of artemether-lumefantrine was conducted in patients aged 6 months and older suffering from uncomplicated falciparum malaria in four different Malian areas during the 2009 malaria transmission season. The polymorphic genetic markers MSP2, MSP1, and Ca1 were used to distinguish between recrudescence and reinfection. Reinfection and recrudescence were then grouped as recurrent infections and analyzed together by PCR-restriction fragment length polymorphism (RFLP) to identify candidate markers for artemether-lumefantrine tolerance in the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multi-drug resistance 1 (pfmdr1) gene. Results: Clinical outcomes in 326 patients (96.7%) were analyzed and the 28-day uncorrected adequate clinical and parasitological response (ACPR) rate was 73.9%. The total PCR-corrected 28-day ACPR was 97.2%. The pfcrt 76T and pfmdr1 86Y population prevalence decreased from 49.3% and 11.0% at baseline (n = 337) to 38.8% and 0% in patients with recurrent infection (n = 85); p = 0.001), respectively. Conclusion: Parasite populations exposed to artemether-lumefantrine in this study were selected toward chloroquine-sensitivity and showed a promising trend that may warrant future targeted reintroduction of chloroquine or/and amodiaquine.

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Lungowe Sitali ◽  
Mulenga C. Mwenda ◽  
John M. Miller ◽  
Daniel J. Bridges ◽  
Moonga B. Hawela ◽  
...  

Abstract Background Anti-malarial resistance is, and continues to be a significant challenge in the fight against malaria and a threat to achieving malaria elimination. In Zambia, chloroquine (CQ), a safe, affordable and well-tolerated drug, was removed from use in 2003 due to high levels of resistance evidenced with treatment failure. This study sought to investigate the prevalence of chloroquine resistance markers in Southern and Western Provinces of Zambia 14 years after the withdrawal of CQ. Methods Data from a cross-sectional, all-age household survey, conducted during the peak malaria transmission season (April–May 2017) was analysed. During the all-age survey, socio-demographic information and coverage of malaria interventions were collected. Consenting individuals were tested for malaria with a rapid diagnostic test and a spot of blood collected on filter paper to create a dried blood spot (DBS). Photo-induced electronic transfer–polymerase chain reaction (PET–PCR) was used to analyse the DBS for the presence of all four malaria species. Plasmodium falciparum positive samples were analysed by high resolution melt (HRM) PCR to detect the presence of genotypic markers of drug resistance in the P. falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multi-drug resistance (Pfmdr) genes. Results A total of 181 P. falciparum positive samples were examined for pfcrt K76T and MDR N86. Of the 181 samples 155 successfully amplified for Pfcrt and 145 for Pfmdr N86. The overall prevalence of CQ drug-resistant parasites was 1.9% (3/155), with no significant difference between the two provinces. No N86Y/F mutations in the Pfmdr gene were observed in any of the sample. Conclusion This study reveals the return of CQ sensitive parasites in Southern and Western Provinces of Zambia 14 years after its withdrawal. Surveillance of molecular resistant markers for anti-malarials should be included in the Malaria Elimination Programme so that resistance is monitored country wide.


2012 ◽  
Vol 109 (32) ◽  
pp. 13052-13057 ◽  
Author(s):  
D. J. Park ◽  
A. K. Lukens ◽  
D. E. Neafsey ◽  
S. F. Schaffner ◽  
H.-H. Chang ◽  
...  

Parasitology ◽  
1989 ◽  
Vol 98 (S1) ◽  
pp. S69-S86 ◽  
Author(s):  
W. I. Morrison

SummaryParasitic diseases inflict major losses on livestock production throughout the world. Currently, control of the diseases relies largely on prophylactic or therapeutic application of anti-parasitic drugs. In many instances, these measures are only partially effective. Moreover, they must be applied frequently, are therefore costly and time-consuming, and lead to the selection of drug resistance within the parasite populations. Thus, it has been recognized for several decades that effective methods of vaccination against parasitic diseases would have a major impact on livestock production. However, despite considerable efforts over the last 30 years, only a few parasite vaccines are currently in use and all of these involve the administration of live organisms.


PLoS Genetics ◽  
2017 ◽  
Vol 13 (10) ◽  
pp. e1007065 ◽  
Author(s):  
Aimee R. Taylor ◽  
Stephen F. Schaffner ◽  
Gustavo C. Cerqueira ◽  
Standwell C. Nkhoma ◽  
Timothy J. C. Anderson ◽  
...  

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