Citation

BibTex format

@article{Ogwang:2024:10.1128/aac.01576-23,
author = {Ogwang, R and Osoti, V and Wamae, K and Ndwiga, L and Muteru, K and Ningwa, A and Tuju, J and Kinyanjui, S and Osier, F and Marsh, K and Bejon, P and Idro, R and Ochola-Oyier, LI},
doi = {10.1128/aac.01576-23},
journal = {Antimicrob Agents Chemother},
title = {A retrospective analysis of P. falciparum drug resistance markers detects an early (2016/17) high prevalence of the k13 C469Y mutation in asymptomatic infections in Northern Uganda.},
url = {http://dx.doi.org/10.1128/aac.01576-23},
volume = {68},
year = {2024}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The emergence of drug-resistant Plasmodium falciparum parasites in sub-Saharan Africa will substantially challenge malaria control. Here, we evaluated the frequency of common drug resistance markers among adolescents from Northern Uganda with asymptomatic infections. We used an established amplicon deep sequencing strategy to screen dried blood spot samples collected from 2016 to 2017 during a reported malaria epidemic within the districts of Kitgum and Pader in Northern Uganda. We screened single-nucleotide polymorphisms within: kelch13 (Pfk13), dihydropteroate synthase (Pfdhps), multidrug resistance-1 (Pfmdr1), dihydrofolate reductase (Pfdhfr), and apical membrane antigen (Pfama1) genes. Within the study population, the median age was 15 years (14.3-15.0, 95% CI), and 54.9% (78/142) were Plasmodium positive by 18S rRNA qPCR, which were subsequently targeted for sequencing analysis. We observed a high frequency of resistance markers particularly for sulfadoxine-pyrimethamine (SP), with no wild-type-only parasites observed for Pfdhfr (N51I, C59R, and S108N) and Pfdhps (A437G and K540E) mutations. Within Pfmdr1, mixed infections were common for NF/NY (98.5%). While for artemisinin resistance, in kelch13, there was a high frequency of C469Y (34%). Using the pattern for Pfama1, we found a high level of polygenomic infections with all individuals presenting with complexity of infection greater than 2 with a median of 6.9. The high frequency of the quintuple SP drug-resistant parasites and the C469Y artemisinin resistance-associated mutation in asymptomatic individuals suggests an earlier high prevalence than previously reported from symptomatic malaria surveillance studies (in 2016/2017). Our data demonstrate the urgency for routine genomic surveillance programs throughout Africa and the value of deep sequencing.
AU - Ogwang,R
AU - Osoti,V
AU - Wamae,K
AU - Ndwiga,L
AU - Muteru,K
AU - Ningwa,A
AU - Tuju,J
AU - Kinyanjui,S
AU - Osier,F
AU - Marsh,K
AU - Bejon,P
AU - Idro,R
AU - Ochola-Oyier,LI
DO - 10.1128/aac.01576-23
PY - 2024///
TI - A retrospective analysis of P. falciparum drug resistance markers detects an early (2016/17) high prevalence of the k13 C469Y mutation in asymptomatic infections in Northern Uganda.
T2 - Antimicrob Agents Chemother
UR - http://dx.doi.org/10.1128/aac.01576-23
UR - https://www.ncbi.nlm.nih.gov/pubmed/39136465
VL - 68
ER -

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