Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017–2019

Malaria Journal

Christiane Prosser¹  Rhoda Namubiru²  Charles Karamagi²  Joan K. Nakayaga²  Sam Nsobya³  Moses R. Kamya³  Adoke Yeka³  Joaniter I. Nankabirwa³  Bosco B. Agaba⁴  Chae Seung Lim⁵  Bora Lee⁶  Sungho Won⁶  Samuel Gonahasa⁷  Emmanuel Arinaitwe⁷  John Kissa⁸  Jimmy Opigo⁹  Karen Anderson^1,10  Karryn Gresty^1,10  David Smith^1,10  Qin Cheng^1,10  Paul Mbaka^1,11  Jane Cunningham^1,12 

[1] Australian Defence Force Malaria and Infectious Disease Institute, Enoggera, Australia;College of Health Sciences, Makerere University, Kampala, Uganda;College of Health Sciences, Makerere University, Kampala, Uganda;Infectious Diseases Research Collaboration, Kampala, Uganda;College of Health Sciences, Makerere University, Kampala, Uganda;National Malaria Control Division, Kampala, Uganda;Department of Laboratory Medicine, College of Health Sciences, Korea University, Seoul, South Korea;Department of Public Health Sciences, Seoul National University, Seoul, South Korea;Infectious Diseases Research Collaboration, Kampala, Uganda;National Health Information Division, Ministry of Health, Kampala, Uganda;National Malaria Control Division, Kampala, Uganda;QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia;Australian Defence Force Malaria and Infectious Disease Institute, Enoggera, Australia;World Health Organization Country Office, Kampala, Uganda;World Health Organization, Geneva, Switzerland;

关键词: Malaria rapid diagnostic tests;    Plasmodium falciparum;    Histidine rich protein 2;    Histidine rich protein 3;    Gene deletion;    Deoxyribonucleic acid;    Microscopy;   

DOI  :  10.1186/s12936-020-03362-x

来源: Springer

【 摘 要 】

BackgroundHistidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda.MethodsThree-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR.ResultsOverall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6–13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4–5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7–20.0%) compared to the western region 3.1% (95% CI 0.8–7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02–23.55), p = 0.003.ConclusionsThis is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs.

【 授权许可】

CC BY