Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria

Author:

Chijioke-Nwauche Ifeyinwa12,Oguike Mary C2,Nwauche Chijioke A34,Beshir Khalid B2,Sutherland Colin J2ORCID

Affiliation:

1. Department of Clinical Pharmacy and Management, Faculty of Pharmaceutical Sciences, University of Port Harcourt, PMB 5323 Choba, Rivers State, Nigeria

2. Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

3. Department of Haematology, Blood Transfusion and Immunology, College of Health Sciences, University of Port Harcourt, PMB 5323 Choba, Rivers State, Nigeria

4. Centre for Malaria Research and Phytomedicine, University of Port Harcourt, PMB 5323 Choba, Rivers State, Nigeria

Abstract

Abstract Background In Nigeria, indiscriminate use of antimalarial drugs may contribute to the threat of drug resistance, but this has not been evaluated among people living with human immunodeficiency virus (HIV). Methods HIV-positive adults attending a university hospital HIV clinic and HIV-negative adult volunteers from the university hospital community with a positive blood film were treated with artemether–lumefantrine. Parasite DNA from before and after treatment was polymerase chain reaction amplified to identify molecular markers of drug susceptibility. Results The pfcrt76T genotype was prevalent among both HIV-positive and HIV-negative participants (78.6% and 68.2%, respectively). Three new mutations in the pfmdr1 gene—F73S, S97L and G165R—and the uncommon pfdhps S436F variant were detected, whereas pfdhps K540E and pfdhfr I164L were absent. The A437G allele of pfdhps predominated (62/66 [94%]). The I431 V mutation was found in 19 of 66 pretreatment pfdhps sequences (28.8%). The pfmdr1 86N allele was significantly more common at day 3 post-treatment than at baseline (odds ratio 8.77 [95% confidence interval 1.21 to 380]). Conclusions We found evidence of continued chloroquine use among HIV-positive individuals. Selection for the pfmdr1 86N after artemether–lumefantrine treatment was observed, indicating a possible threat to antimalarial efficacy in the study area. The complexity of pfdhps haplotypes emphasises the need for careful monitoring of anti-folate susceptibility in Nigeria.

Funder

Rivers State Sustainable Development Agency

Public Health England

UK Medical Research Council

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Public Health, Environmental and Occupational Health,General Medicine,Parasitology

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