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Progressive increase in point mutations associated with chloroquine resistance in Plasmodium falciparum isolates from
Pooja Mittra1, Sumiti Vinayak, Hina Chandawat
1Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India.
Background:
Effective malaria control programs require continuous monitoring of drug pressure in the field, using molecular markers.
Methods:
We used sequence analysis to investigate the pfcrt and pfmdr1 mutations in Indian Plasmodium falciparum isolates. To evaluate the chloroquine drug pressure in the field, isolates were collected from 5 different areas at 2 time points, with an interval of 2 years.
Results:
In 265 P. falciparum isolates, pfcrt mutations were observed at codons 72, 74, 75, 76, and 220, resulting in 8 different genotypes: SMNTS (61.89%), CIETS (12.08%), CMNKS (0.38%), CMNTA (2.64%), CMNTS (4.91%), SMNTA (0.38%), CIDTS (2.26%), and wild-type CMNKA (15.47%). During the 2-year period, there was a significant decrease in the number of isolates with the SMNTS genotype and an increase in the number of isolates with the highly chloroquine-resistant pfcrt genotype CIETS (P < .05). The N86Y mutation was less prevalent (30.13%) than the Y184F mutation (99.16%) in the pfmdr1 gene in 239 isolates, but the number of isolates with the N86Y mutation increased significantly during the 2-year period (P < .05). The number of isolates with higher total numbers of pfcrt and pfmdr1 2-loci mutations, therefore, increased significantly during this period. There was a regional bias in the mutation rate of these genes, because isolates from areas where chloroquine resistance was high had higher numbers of 2-loci mutations, and areas where chloroquine resistance was low had isolates with lower numbers of 2-loci mutations.
Conclusion:
There was a temporal increase in the number of pfcrt and pfmdr1 2-loci mutations, and this led to the higher level of chloroquine resistance. This is a cause for concern for the antimalarial drug policy in India.
Insights
Molecular markers show increasing Plasmodium falciparum resistance to chloroquine in India. Monitoring pfcrt and pfmdr1 mutations is crucial for malaria control drug policy.
Area of Science:
- Molecular parasitology
- Antimalarial drug resistance
Background:
- Effective malaria control relies on monitoring drug pressure using molecular markers.
- Plasmodium falciparum resistance to antimalarials is a significant global health challenge.
Purpose of the Study:
- To investigate pfcrt and pfmdr1 gene mutations in Indian Plasmodium falciparum isolates.
- To evaluate chloroquine drug pressure by analyzing molecular markers over time.
Main Methods:
- Sequence analysis of pfcrt and pfmdr1 genes in Plasmodium falciparum isolates.
- Collection of isolates from 5 distinct regions across two time points, separated by a 2-year interval.
Main Results:
- Observed 8 pfcrt genotypes, with a significant increase in the highly chloroquine-resistant CIETS genotype.
- pfmdr1 gene showed increased prevalence of the N86Y mutation over the 2-year period.
- A significant rise in combined pfcrt and pfmdr1 mutations correlated with regional chloroquine resistance levels.
Conclusions:
- Temporal increase in pfcrt and pfmdr1 mutations indicates rising chloroquine resistance in India.
- This trend poses a concern for current antimalarial drug policy and necessitates adaptive strategies.
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