Plasmodium Species Infecting Children Presenting with Malaria in Uganda

Asua, Victor; Tukwasibwe, Stephen; Conrad, Melissa D.; Walakira, Andrew; Nankabirwa, Joaniter I.; Mugenyi, Levicatus; Kamya, Moses R.; Nsobya, Samuel L.; Rosenthal, Philip J.

doi:10.4269/ajtmh.17-0345

Cited by 36 publications

(35 citation statements)

References 25 publications

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“…Genomic DNA was extracted from blood spots using Chelex 100, as previously described (53). Pfmdr1, pfcrt, pfdhfr, and pfdhps polymorphisms of interest were characterized by PCR and ligase detection reaction-fluorescent microsphere assays, as previously described (54), with minor modification to incorporate nested PCR (48).…”

Section: Methodsmentioning

confidence: 99%

Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda

Asua

Vinden

Conrad

et al. 2019

Antimicrob Agents Chemother

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The potential spread of antimalarial drug resistance to Africa, in particular for artemisinins and key partner drugs, is a major concern. We surveyed Plasmodium falciparum genetic markers associated with drug sensitivity on 3 occasions at ∼6-month intervals in 2016 and 2017 at 10 sites representing a range of epidemiological settings in Uganda. For putative drug transporters, we found continued evolution toward wild-type sequences associated with increased sensitivity to chloroquine. For pfcrt K76T, by 2017 the prevalence of the wild type was >60% at all sites and >90% at 6 sites. For the pfmdr1 N86Y and D1246Y alleles, wild type prevalence ranged from 80 to 100%. We found low prevalence of K13 propeller domain mutations, which are associated with artemisinin resistance in Asia, but one mutation previously identified in northern Uganda, 675V, was seen in 2.0% of samples, including 5.5% of those from the 3 northernmost sites. Amplification of the pfmdr1 and plasmepsin2 genes, associated elsewhere with decreased sensitivity to lumefantrine and piperaquine, respectively, was seen in <1% of samples. For the antifolate targets pfdhfr and pfdhps, 5 mutations previously associated with resistance were very common, and the pfdhfr 164L and pfdhps 581G mutations associated with higher-level resistance were seen at multiple sites, although prevalence did not clearly increase over time. Overall, changes were consistent with the selective pressure of the national treatment regimen, artemether-lumefantrine, with increased sensitivity to chloroquine, and with poor efficacy of antifolates. Strong evidence for resistance to artemisinins was not seen. Continued surveillance of markers that predict antimalarial drug sensitivity is warranted.

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Section: Methodsmentioning

confidence: 99%

Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda

Asua

Vinden

Conrad

et al. 2019

Antimicrob Agents Chemother

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“…However, Duffy-negative individuals have been diagnosed with P. vivax infections throughout Africa (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), in part, because of the development of a sensitive real-time PCR test for P. vivax.…”

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confidence: 99%

Transcriptome profiling ofPlasmodium vivaxinSaimirimonkeys identifies potential ligands for invasion

Gunalan

Sá

Barros

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Unlike the case in Asia and Latin America,Plasmodium vivaxinfections are rare in sub-Saharan Africa due to the absence of the Duffy blood group antigen (Duffy antigen), the only known erythrocyte receptor for theP. vivaxmerozoite invasion ligand, Duffy binding protein 1 (DBP1). However,P. vivaxinfections have been documented in Duffy-negative individuals throughout Africa, suggesting thatP. vivaxmay use ligands other than DBP1 to invade Duffy-negative erythrocytes through other receptors. To identify potentialP. vivaxligands, we compared parasite gene expression inSaimiriandAotusmonkey erythrocytes infected withP. vivaxSalvador I (Sal I). DBP1 bindsAotusbut does not bind toSaimirierythrocytes; thus,P. vivaxSal I must invadeSaimirierythrocytes independent of DBP1. Comparing RNA sequencing (RNAseq) data for late-stage infections inSaimiriandAotuserythrocytes when invasion ligands are expressed, we identified genes that belong to tryptophan-rich antigen and merozoite surface protein 3 (MSP3) families that were more abundantly expressed inSaimiriinfections compared withAotusinfections. These genes may encode potential ligands responsible forP. vivaxinfections of Duffy-negative Africans.

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“…In this issue of AJTMH , Asua et al 7 report their observations related to treatment-seeking children from health centers in 10 of Uganda’s 111 districts. From the total of 499 samples, malaria microscopy and rapid diagnostic tests (RDTs) were used to perform preliminary analyses; PCR (18S rRNA) was used to confirm and increase species specificity of their diagnoses.…”

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confidence: 99%

“…Although the majority of malaria cases involved Plasmodium falciparum , 7.8% were nonfalciparum infections and P. vivax was found in four children (0.8%). 7 These authors use their observations to call attention to the importance of species-specific diagnosis to inform adequate antimalarial drug treatment. In particular, because their diagnosis detected P. vivax and P. ovale infections, treatment to cure patients completely of liver stage hypnozoites would require use of primaquine.…”

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confidence: 99%

“…In particular, because their diagnosis detected P. vivax and P. ovale infections, treatment to cure patients completely of liver stage hypnozoites would require use of primaquine. 7 Their paper raises a wider concern that malaria elimination will require the ability to diagnose and develop strategies against all human malaria species being transmitted within endemic regions.…”

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