TY - JOUR
T1 - Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017-2019
AU - Bosco, Agaba B.
AU - Anderson, Karen
AU - Gresty, Karryn
AU - Prosser, Christiane
AU - Smith, David
AU - Nankabirwa, Joaniter I.
AU - Nsobya, Sam
AU - Yeka, Adoke
AU - Opigo, Jimmy
AU - Gonahasa, Samuel
AU - Namubiru, Rhoda
AU - Arinaitwe, Emmanuel
AU - Mbaka, Paul
AU - Kissa, John
AU - Won, Sungho
AU - Lee, Bora
AU - Lim, Chae Seung
AU - Karamagi, Charles
AU - Cunningham, Jane
AU - Nakayaga, Joan K.
AU - Kamya, Moses R.
AU - Cheng, Qin
N1 - Funding Information:
Funding for parasite gene deletion analysis was supported by the US Armed Forces Health Surveillance Branch (AFHSB) Global Emerging Infections Surveillance (GEIS) section and the Fogarty International Center of the National Institutes of Health under Award Number D43TW010526. JIN is supported by the Fogarty International Center (Emerging Global Leader Award grant number K43TW010365). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
PY - 2020/8/26
Y1 - 2020/8/26
N2 - Background: Histidine-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. Methods: Three-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. Results: Overall, 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. Conclusions: This 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.
AB - Background: Histidine-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. Methods: Three-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. Results: Overall, 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. Conclusions: This 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.
KW - Deoxyribonucleic acid
KW - Gene deletion
KW - Histidine rich protein 2
KW - Histidine rich protein 3
KW - Malaria rapid diagnostic tests
KW - Microscopy
KW - Plasmodium falciparum
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U2 - 10.1186/s12936-020-03362-x
DO - 10.1186/s12936-020-03362-x
M3 - Article
C2 - 32843041
AN - SCOPUS:85089931850
VL - 19
JO - Malaria Journal
JF - Malaria Journal
SN - 1475-2875
IS - 1
M1 - 300
ER -