Browsing by Author "Bikaitwoha, Everd Maniple"

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    Assessment of different genotyping markers and algorithms for distinguishing Plasmodium falciparum recrudescence from reinfection in Uganda
    (Research Square, 2025-02-05) Mwesigwa, Alex; Golumbeanu, Monica; Jones, Sam; Cantoreggi, Sara L.; Musinguzi, Benson; Nankabirwa, Joaniter I.; Bikaitwoha, Everd Maniple; Kalyango, Joan N; Karamagi, Charles; Plucinski, Mateusz; Nsobya, Samuel L.; Nsanzabana, Christian; Byakika-Kibwika, Pauline
    Antimalarial therapeutic efficacy studies are vital for monitoring the efficacy of antimalarial drugs in malaria-endemic regions. The WHO recommends genotyping of polymorphic markers including msp-1, msp-2, and glurp to aid distinguishing recrudescences from reinfections. Recently, WHO proposed replacing glurp with microsatellites (Poly-α, PfPK2, TA1). However, suitable combinations with msp-1 and msp-2 have not been systematically assessed. Additionally, the performance of different algorithms for classifying recrudescence is unclear. This study investigated various microsatellites alongside msp-1 and msp-2 for molecular correction and compared genotyping algorithms across three malaria-endemic areas in Uganda. Microsatellites 313, Poly-α, and 383 exhibited the highest diversity, while PfPK2 and Poly-α revealed elevated multiplicities of infection across all sites. The 3/3 match-counting algorithm classified fewer recrudescences than the ≥ 2/3, and Bayesian algorithms at both ≥ 0.7 and ≥ 0.8 probability cutoffs. The msp-1/msp-2/2490 combination identified more recrudescences using the ≥ 2/3 and 3/3 algorithms in the artemether-lumefantrine (AL) treatment arm, while msp-1/msp-2/glurp combination identified more cases of recrudescence using the ≥ 2/3 in the dihydroartemisinin-piperaquine (DP) arm. Microsatellites PfPK2 and Poly-α, potentially sensitive to detecting minority clones, are promising replacements for glurp. Discrepancies in recrudescence classification between match-counting and Bayesian algorithms highlight the need for standardized PCR correction practices.
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    Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda
    (Springer Nature, 2024-11-14) Mwesigwa, Alex; Ocan, Moses; Cummings, Bryan; Musinguzi, Benson; Kiyaga, Shahid; Kiwuwa, Steven M.; Okoboi, Stephen; Castelnuovo, Barbara; Bikaitwoha, Everd Maniple; Kalyango, Joan N.; Karamagi, Charles; Nankabirwa, Joaniter I.; Nsobya, Samuel L.; Byakika-Kibwika, Pauline
    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 FST 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.