scholarly journals Superinfection and the evolution of resistance to antimalarial drugs

2012 ◽  
Vol 279 (1743) ◽  
pp. 3834-3842 ◽  
Author(s):  
Eili Y. Klein ◽  
David L. Smith ◽  
Ramanan Laxminarayan ◽  
Simon Levin

A major issue in the control of malaria is the evolution of drug resistance. Ecological theory has demonstrated that pathogen superinfection and the resulting within-host competition influences the evolution of specific traits. Individuals infected with Plasmodium falciparum are consistently infected by multiple parasites; however, while this probably alters the dynamics of resistance evolution, there are few robust mathematical models examining this issue. We developed a general theory for modelling the evolution of resistance with host superinfection and examine: (i) the effect of transmission intensity on the rate of resistance evolution; (ii) the importance of different biological costs of resistance; and (iii) the best measure of the frequency of resistance. We find that within-host competition retards the ability and slows the rate at which drug-resistant parasites invade, particularly as the transmission rate increases. We also find that biological costs of resistance that reduce transmission are less important than reductions in the duration of drug-resistant infections. Lastly, we find that random sampling of the population for resistant parasites is likely to significantly underestimate the frequency of resistance. Considering superinfection in mathematical models of antimalarial drug resistance may thus be important for generating accurate predictions of interventions to contain resistance.

2021 ◽  
Vol 15 (12) ◽  
pp. 3273-3276
Author(s):  
Sana Hafeez ◽  
Haleema Sajid ◽  
Farouk Qamar Malik ◽  
Imran Ali Zaidi ◽  
Sobia Niaz ◽  
...  

Background: Tuberculosis (TB) is fatal and life threatening infectious disease. The transmission rate of tuberculosis is very high. Various drugs are used as treatment for TB. Recently it has been observed that one of the most important factor for fast TB spread is development of anti-TB drug resistant mycobacterium tuberculosis (MTB). Various combination of drugs like isoniazid (INH), rifampicin (RIF), Streptomycin(SM), pyrazinamide (PZA) or ethambutol (EMB) are in global use for TB treatment. Improper usage of these drugs makes the person prone to develop anti-TB drug resistant tuberculosis. Aim: To evaluate association of embB gene with ethambutol resistance in Mycobacterium Tuberculosis. Methods: 104 Specimens of sputum from suspected tuberculosis patients were processed for inoculation in Lowenstein J Medium after it has been decontaminated properly. Kit method by using QIAamp DNA Mini kit was utilized for extraction of DNA. Then region from base 6953 to 10249 of embB gene was amplified through PCR and then followed by sequencing with the aid of softwares blast2seq and ClustalW2. Three primer sets were utilized to amplify embB gene. Ethambutol (EMB) Resistant MTB specimens were processed to study mutation in embB gene. Results: Out of the total 104 sputum specimens, 14 samples were found to have ethambutol resistance. These 14 samples were then processed for mutational analysis. DNA sequence analysis of these 14 samples confirmed embB gene mutation in 10 samples. Mutational analysis revealed that 08 samples showed mutation at codon 306 and two samples showed mutation at 319 codon. The reported mutation Methionine →Isoleucine was seen in 07 samples with ATG codon replaced by ATA codon at codon position 306. One sample showed mutation as Methionine →Isoleucine with ATG codon replaced by ATC codon at codon position 306. Two samples showed mutation as Tyrosine →Serine with TAT codon replaced by TCT at 319 codon position in embB gene. Conclusion: This study concludes that mutation of certain genes particularly point mutation of embB gene at codon 306 and 319 is associated with drug resistance of ethambutol in ethambutol resistant mycobacterium tuberculosis patients. Keywords: Ethambutol, embB gene, Mycobacterium tuberculosis.


2010 ◽  
Vol 42 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Valérie Andriantsoanirina ◽  
Didier Ménard ◽  
Luciano Tuseo ◽  
Rémy Durand

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Ruimin Zhou ◽  
Chengyun Yang ◽  
Suhua Li ◽  
Yuling Zhao ◽  
Ying Liu ◽  
...  

ABSTRACT Angola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as pfcrt, pfmdr1, pfdhfr, pfdhps, and K13. This study evaluated the drug resistance of the 180 imported Plasmodium falciparum isolates from Angola via nested PCR using Sanger sequencing. The prevalences of pfcrt C72V73M74N75K76, pfmdr1 N86Y184S1034N1042D1246, pfdhfr A16N51C59S108D139I164, and pfdhps S436A437A476K540A581 were 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I, and Q613E) and one synonymous (R471R) mutation of K13 were found, the prevalences of which were 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, and pfdhps were generally shown as multiple mutations. The mutant prevalence of pfcrt reduced gradually, but pfdhfr and pfdhps still showed high mutant prevalence, while pfmdr1 was relatively low. The mutation of the K13 gene was rare. Molecular surveillance of artemisinin (ART) resistance will be used as a tool to evaluate the real-time efficacy of the artemisinin-based combination therapies (ACTs) and the ART resistance situation.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Monday Tola ◽  
Olumide Ajibola ◽  
Emmanuel Taiwo Idowu ◽  
Olusesan Omidiji ◽  
Samson Taiwo Awolola ◽  
...  

Abstract Objective Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1–61 years old from South-west Nigeria. Results Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.


Acta Tropica ◽  
2016 ◽  
Vol 157 ◽  
pp. 158-161 ◽  
Author(s):  
Michela Menegon ◽  
Abduselam M. Nurahmed ◽  
Albadawi A. Talha ◽  
Bakri Y.M. Nour ◽  
Carlo Severini

Acta Tropica ◽  
2013 ◽  
Vol 126 (1) ◽  
pp. 84-87 ◽  
Author(s):  
Sasmita Kumari Das Sutar ◽  
Gunanidhi Dhangadamajhi ◽  
Shantanu Kumar Kar ◽  
Manoranjan Ranjit

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