Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda

Alex Mwesigwa^{1

2}, Moses Ocan³, Bryan Cummings⁴, Benson Musinguzi^{5

6}, Shahid Kiyaga⁶, Steven M Kiwuwa⁷, Stephen Okoboi⁸, Barbara Castelnuovo⁸, Everd Maniple Bikaitwoha⁹, Joan N Kalyango¹⁰, Charles Karamagi¹⁰, Joaniter I Nankabirwa^{10

11}, Samuel L Nsobya¹¹, Pauline Byakika-Kibwika^{8

12

13}

Affiliations

¹ Clinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda. mwesigwaalex@gmail.com.
² Department of Microbiology and Immunology, School of Medicine, Kabale University, P. O Box 314, Kabale, Uganda. mwesigwaalex@gmail.com.
³ Department of Pharmacology & Therapeutics, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
⁴ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 655 W. Baltimore St, Baltimore, MD, 21201, USA.
⁵ Departent of Medical Laboratory Science, Faculty of Health Sciences, Muni University, P.O Box 725, Arua, Uganda.
⁶ Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
⁷ Department of Biochemistry, School of Biomedical Sciences, College of Health Sciences, Makerere, University, P.O. Box 7072, Kampala, Uganda.
⁸ Infectious Diseases Institute, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.
⁹ Department of Community Health, School of Medicine, Kabale University, P. O Box 314, Kabale, Uganda.
¹⁰ Clinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.
¹¹ Infectious Diseases Research Collaboration, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
¹² Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.
¹³ Mbarara University of Science and Technology, Mbarara, Uganda.

PMID: 39543779
PMCID: PMC11562702
DOI: 10.1186/s41182-024-00656-7

Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda

Alex Mwesigwa et al. Trop Med Health. 2024.

. 2024 Nov 14;52(1):86.

doi: 10.1186/s41182-024-00656-7.

Authors

Affiliations

¹ Clinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda. mwesigwaalex@gmail.com.
² Department of Microbiology and Immunology, School of Medicine, Kabale University, P. O Box 314, Kabale, Uganda. mwesigwaalex@gmail.com.
³ Department of Pharmacology & Therapeutics, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
⁴ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 655 W. Baltimore St, Baltimore, MD, 21201, USA.
⁵ Departent of Medical Laboratory Science, Faculty of Health Sciences, Muni University, P.O Box 725, Arua, Uganda.
⁶ Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
⁷ Department of Biochemistry, School of Biomedical Sciences, College of Health Sciences, Makerere, University, P.O. Box 7072, Kampala, Uganda.
⁸ Infectious Diseases Institute, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.
⁹ Department of Community Health, School of Medicine, Kabale University, P. O Box 314, Kabale, Uganda.
¹⁰ Clinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.
¹¹ Infectious Diseases Research Collaboration, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
¹² Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, P. O. Box 7072, Kampala, Uganda.
¹³ Mbarara University of Science and Technology, Mbarara, Uganda.

PMID: 39543779
PMCID: PMC11562702
DOI: 10.1186/s41182-024-00656-7

Abstract

Background: Plasmodium falciparum (P. falciparum) remains a significant public health challenge globally, especially in sub-Saharan Africa (SSA), where it accounts for 99% of all malaria infections. The outcomes of P. falciparum infection vary, ranging from asymptomatic to severe, and are associated with factors such as host immunity, parasite genetic diversity, and multiplicity of infection (MOI). Using seven neutral microsatellite markers, the current study investigated P. falciparum genetic diversity and MOI in both asymptomatic and symptomatic malaria individuals in Uganda.

Methods: This cross-sectional study analyzed 225 P. falciparum isolates from both asymptomatic and symptomatic malaria patients, ranging in age from 6 months to ≥ 18 years. P. falciparum genetic diversity, MOI, and multi-locus linkage disequilibrium (LD) were assessed through genotyping of seven neutral microsatellite markers: Poly-α, TA1, TA109, PfPK2, 2490, C2M34-313, and C3M69-383. Genetic data analysis was performed using appropriate genetic analysis software.

Results: P. falciparum infections exhibited high genetic diversity in both asymptomatic and symptomatic individuals. The mean expected heterozygosity (He) ranged from 0.79 in symptomatic uncomplicated malaria cases to 0.81 in asymptomatic individuals. There was no significant difference (p = 0.33) in MOI between individuals with asymptomatic and symptomatic infections, with the mean MOI ranging from 1.92 in symptomatic complicated cases to 2.10 in asymptomatic individuals. Polyclonal infections were prevalent, varying from 58.5% in symptomatic complicated malaria to 63% in symptomatic uncomplicated malaria cases. A significant linkage disequilibrium (LD) was observed between asymptomatic and symptomatic uncomplicated/complicated infections (p < 0.01). Genetic differentiation was low, with F_ST values ranging from 0.0034 to 0.0105 among P. falciparum parasite populations in asymptomatic and symptomatic uncomplicated/complicated infections.

Conclusion: There is a high level of P. falciparum genetic diversity and MOI among both symptomatic and asymptomatic individuals in Uganda. Asymptomatic carriers harbor a diverse range of parasites, which poses challenges for malaria control and necessitates targeted interventions to develop effective strategies.

Keywords: P. falciparum; Genetic diversity; Malaria; Multiplicity of infection; Uganda.

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Conflict of interest statement

Declarations Ethics approval and consent to participate This study utilized secondary data without participant interaction. Study approval and a waiver of consent were provided by the Makerere University School of Medicine Institutional Review Board (# Mak-SOMREC-2021-152) and the Uganda National Council for Science and Technology (# HS2744ES). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests.

Figures

**Fig. 1**
The allele frequencies of the genotyped markers assessed among individuals with asymptomatic (blue), symptomatic uncomplicated (green) and complicated (red) malaria infections. The vertical axis represents the frequencies of individual alleles, whereas the horizontal axis represents the base pairs of each allele. *Chr* chromosome, bp base pair

See this image and copyright information in PMC

References

1. WHO. World malaria report 2022. Geneva: World Health Organization; 2022.
1. Bartoloni A, Zammarchi L. Clinical aspects of uncomplicated and severe malaria. Mediterr J Hematol Infect Dis. 2012;4(1): e2012026. - PMC - PubMed
1. Laishram DD, Sutton PL, Nanda N, Sharma VL, Sobti RC, Carlton JM, et al. The complexities of malaria disease manifestations with a focus on asymptomatic malaria. Malar J. 2012;11:1–15. - PMC - PubMed
1. Bendixen M, Msangeni H, Pedersen B, Shayo D, Bedker R. Diversity of Plasmodium falciparum populations and complexity of infections in relation to transmission intensity and host age: a study from the Usambara Mountains, Tanzania. Trans R Soc Trop Med Hyg. 2001;95(2):143–8. - PubMed
1. Gray K-A, Dowd S, Bain L, Bobogare A, Wini L, Shanks GD, et al. Population genetics of Plasmodium falciparum and Plasmodium vivax and asymptomatic malaria in Temotu Province Solomon Islands. Malar J. 2013;12:1–10. - PMC - PubMed

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Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda

Affiliations

Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous