Browsing by Author "Castelnuovo, Barbara"

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    Genetic diversity and population structure of Plasmodium falciparum across areas of varied malaria transmission intensities in Uganda.
    (Malaria Journal, 2025) Mwesigwa, Alex; Tukwasibwe, Stephen; Cummings, Bryan; Kawalya, Hakiimu; Kiyaga, Shahiid; Okoboi, Stephen; Castelnuovo, Barbara; Bikaitwoha, Everd Maniple; Kalyango, Joan N.; Nsobya, Samuel L.; Karamagi, Charles; Byakika‑Kibwika, Pauline; Nankabirwa, Joaniter I.
    Background: Malaria remains a significant global health threat, with sub-Saharan Africa (SSA) bearing the highest burden of the disease. Plasmodium falciparum is the predominant species in the region, leading to substantial morbidity and mortality. Despite intensified control efforts over the last two decades, P. falciparum genetic diversity and multiplicity of infections (MOI) continue to pose significant challenges to malaria elimination in the region. This study assessed P. falciparum genetic diversity and population structure in areas with low, medium, and high malaria transmission intensities in Uganda. Methods: A total of 288 P. falciparum-positive samples from children (6 months to 10 years) and adults (≥ 18 years) living in Jinja (low transmission), Kanungu (medium transmission), and Tororo (high transmission) were genotyped using seven neutral microsatellite markers. Genetic diversity was assessed based on the number of alleles (Na), allelic richness (Ar), and expected heterozygosity (He). Population structure was assessed using the fixation index, analysis of molecular variance (AMOVA), and clustering analysis. Results: High P. falciparum genetic diversity was observed across all study sites, with Kanungu exhibiting the highest mean He (0.81 ± 0.14), while Jinja and Tororo had lower mean He (0.78 ± 0.16). P. falciparum MOI varied significantly,with Tororo showing the highest mean MOI (2.5 ± 0.5) and 70% of samples exhibiting polyclonal infections, compared to Jinja’s mean MOI of 1.9 ± 0.3 and 58% polyclonal infections. Significant multilocus linkage disequilibrium (LD) was noted (p < 0.01), ranging from 0.07 in Tororo to 0.14 in Jinja. Parasite population structure showed minimal genetic differentiation (FST ranged from 0.011 to 0.021) and a low AMOVA value (0.03), indicating high gene flow. Conclusion: This study demonstrates high P. falciparum genetic diversity and MOI but low population structure, suggesting significant parasite gene flow between study sites. This highlights the need for integrated malaria control strategies across areas with varying malaria transmission intensities in Uganda.
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    Plasmodium Falciparum Genetic Diversity and Multiplicity of Infection Among Asymptomatic and Symptomatic Malaria-Infected Individuals in Uganda.
    (Kabale University, 2024) 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
    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 multilocus linkage disequilibrium (LD) were assessed through genotyping of seven neutral microsatellite markers: Polyα, 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 asymp‑ automatic 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.
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    Plasmodium falciparum genetic diversity and multiplicity of infection based on msp‑1, msp‑2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.
    (Kabale University, 2024) Mwesigwa, Alex; Ocan, Moses; Musinguzi, Benson; Nante, Rachel Wangi; Nankabirwa, Joaniter I.; Kiwuwa, Steven M.; Kinengyere, Alison Annet; Castelnuovo, Barbara; Karamagi, Charles; Obuku, Ekwaro A.; Nsobya, Samuel L.; Mbulaiteye, Sam M.; Byakika‐Kibwika, Pauline
    Background In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA. Methods: The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17. Results: The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51–0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of MSP-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%,MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For MSP-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurpwas 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88–2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56–70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%). Conclusion: The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.