Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 10;24(1):5.
doi: 10.1186/s12936-024-05240-2.

Low prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola

Denise Duarte  1 , Francisco Manuel  2 , Ana Dias  3 , Esmeralda Sacato  4 , Elsa Taleingue  4 , Elsa Daniel  4 , Francisco Simão  4 , Luis Varandas  1 , Maria Lina Antunes  2   4 , Fatima Nogueira  5
Affiliations

Low prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola

Denise Duarte et al. Malar J. .

Abstract

Background: Malaria is the parasitic disease with the highest global morbidity and mortality. According to estimates from the World Health Organization (WHO), there were around 249 million cases in 2022, with 3.4% occurring in Angola. The emergence and spread of drug-resistant Plasmodium falciparum have compromised anti-malarial efficacy and threatens malaria elimination campaigns using artemisinin-based combination therapy (ACT). Increased copy number (CNV) of the P. falciparum gene plasmepsin 2 (pfpm2) have been reported to confer parasite tolerance to piperaquine (PPQ) and the multidrug resistance-1 (pfmdr1), resistance to mefloquine (MEF) and decreased susceptibility to lumefantrine (LUM). PPQ, MEF and LUM are ACT partner drugs. Therefore, CNV detection is a useful tool to track ACT resistance risk. The potential for future treatment failure of artemisinin-based combinations (that include PPQ, LUM and AMQ), due to parasite resistance in the region, emphasizes the need for continued molecular surveillance.

Methods: One hundred and nine clinically derived samples were collected at Hospital Central Dr. António Agostinho Neto (HCL) in Lubango, Angola. qPCR targeting the small-subunit 18S rRNA gene was used to confirm P. falciparum infection. Copy number estimates were determined using a SYBR green-based quantitative PCR assay.

Results: Overall, this study revealed a low number of resistance CNVs present in the parasite population at Lubango, for the genes pfmdr1 and pfpm2. Of the 102 samples successfully analysed for pfpm2 10 (9.8%) carried increased CNV and 9/101 (8.9%) carried increased CNV of pfmdr1.

Conclusions: This study provides, for the first time, evidence for the presence of CNVs in the pfpm2 and pfmdr1 genes in P. falciparum isolates from southern Angola.

Keywords: Plasmodium falciparum; pfmdr1; pfpm2; Angola; Lubango; Lumefantrine; Piperaquine.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: DNA samples were collected following individual oral consent and signed informed written consent from all participants or their guardians. Ethical clearance for the work was obtained from: Comité de Ética Independente da Faculdade de Medicina da Universidade Agostinho Neto and by the Hospital Central Dr. António Agostinho Neto (HCL) institutional ethics review committee (deliberation Nº08/2020, on 14 November 2020). Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Summary of sample processing and map of Angola highlighting study site. Pin, Lubango city and malaria incidence areas. Huíla province in dark green
Fig. 2
Fig. 2
Copy number of pfmdr1 and pfpm2 in P. falciparum samples from Lubango. The x-axis represents the each sample, while the y-axis shows the CNV (copy number variation) of each sample for each gene.Inserted table, number of samples with increased copy number of each gene; 3D7 reference strain (pfmdr1 black circle is superimposed to the clear circle corresponding to pfpm2), Dd2 and IPC_6261, control strains; black circles, mean CNV value for pfmdr1 in each sample; clear circles, mean CNV value for pfpm2 in each sample
See this image and copyright information in PMC

References

    1. WHO. World malaria report 2023. Geneva, World Health Organization, 2023. https://www.who.int/teams/global-malaria-programme/reports/world-malaria....
    1. Sacomboio ENM, dos Santos Sebastião C, Salvador ST da C, João JA, Bapolo DVS, Francisco NM, et al. Evaluation of blood cell count parameters as predictors of treatment failure of malaria in Angola: an observational study. PLoS One. 2022;17:e0267671. - PMC - PubMed
    1. Tavares W, Morais J, Martins JF, Scalsky RJ, Stabler TC, Medeiros MM, et al. Malaria in Angola: recent progress, challenges and future opportunities using parasite demography studies. Malar J. 2022;21:396. - PMC - PubMed
    1. Plucinski MM, Dimbu PR, Macaia AP, Ferreira CM, Samutondo C, Quivinja J, et al. Efficacy of artemether–lumefantrine, artesunate–amodiaquine, and dihydroartemisinin–piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in Angola, 2015. Malar J. 2017;16:62. - PMC - PubMed
    1. White NJ. Malaria. In: Finch RG, Greenwood D, Norrby SR, Whitley RJ (eds.). Antibiotic and Chemotherapy. 9th Edn. Saunders Publ. 2010.

MeSH terms

LinkOut - more resources