Mary E Avornyo

Conference 2022 Pre-recorded Presentation

 

Video title

Determination Of The Prevalence Of The Novel Pregnancy Associated SNP In The Dihydropteroate Synthase(DHPS) Gene At Codon 431 In P. Falciparum.

 

Authors and Affiliations

Dr. Nancy Quashie1, Mary Eyi Avornyo1, Philip Opoku-Agyeman1, Selassie Bruku1

1. Noguchi Memorial Institute for Medical Research

 

Abstract

Background

Sulfadoxine-pyrimethamine (SP) is used for malaria chemoprophylaxis for pregnant women and children, although resistance to the drug persists. SP resistance is linked to point mutations in the dihydropteroate synthase gene (dhps) and dihydrofolate reductase genes (dhfr) used for surveillance in malaria endemic countries. Recently, a point mutation in dhps at codon 431 was observed in parasites from pregnant women, however its role in resistance is not known.

Methods

Ninety six (96) dried blood blots collected in 2016 from children aged 9 years and below, with uncomplicated malaria from three sentinel sites in Begoro, Cape Coast, and Navrongo were used in this study. Parasite DNA was extracted followed by PCR and Sanger sequencing of the two genes to detect the mutations. Sequence analysis of good gene sequences did not detect the novel I431V mutation, seen in pregnant women from Cameroon and travelers returning from Nigeria, in the Ghanaian isolates.

Results

Sequence analysis of good gene sequences did not detect the novel I431V mutation, seen in pregnant women from Cameroon and travelers returning from Nigeria, in the Ghanaian isolates. However, other mutations of dhps were observed with 28.4% (27/95) being wild type and dhps mutations at codons A437G, A581G and A613S was 1.1% (1/95) each. New variants at codons 540 (K540N) and 581 (A581A) were the dominant dhps mutations observed with a prevalence of 41.1% (39/95) and 55.8% (53/95) respectively. For dhfr, 75.9% (66/87), 86.2% (75/87) and 85.1% (74/87) of all samples analysed had N51I, C59R and S108N mutant alleles respectively. Novel mutations S108D, N51F and I164R/K were observed in parasite isolates from Navrongo and Cape Coast but in low proportions of 1.1% (1/87). Although the new dhps I431V mutation was not observed in this study, the high prevalence of the molecular markers of SP resistance reiterates the need for continuous surveillance in the country.

Conclusions

The study showed there was a significant rise in dhps/dhfr mutations with the emergence of novel mutations in Ghanaian parasite isolates. The most common mutation for the dhfr gene was C59R, which was found in 86.2% (75/87) of samples, followed by S108N, which was found in 85.1% (75/87) of isolates, and N51I, which was found in 75.9% of samples. S108D, N51F, and I164I/K mutations were discovered to be new. The study showed that among the dhps mutant alleles, A581A was the highest with a pooled prevalence of 55.8% (53/95), followed by K540N at 41.1% (39/95). Other mutations that were observed were S436A, A437G and A613S which occurred in low proportions. There is the also the possibility that the novel polymorphisms identified may play a role in conferring resistance.