Browsing by Author "Nsobya, Samuel L."
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Item Open Access 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, PaulinePlasmodium 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.Item Open Access 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, PaulineBackground 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.Item Open Access Temporal Changes in Plasmodium Falciparum Genetic Diversity and Multiplicity of Infection Across Three Areas of Varying Malaria Transmission Intensities in Uganda.(Kabale University, 2025) Mwesigwa, Alex; Kiwuwa, Steven M.; Musinguzi, Benson; Kawalya, Hakiim; Katumba, James Davis; Baguma, Andrew; Mutuku, Irene M.; Adebayo, Ismail Abiola; Nsobya, Samuel L.; Byakika‐Kibwika, Pauline; Kalyango, Joan N.; Karamagi, Charles; Nankabirwa, Joaniter I.Background: Malaria is a significant public health challenge in Uganda, with Plasmodium falciparum (P. falciparum) responsible for most malaria infections. The high genetic diversity and multiplicity of infection (MOI) associated with P. falciparum complicate treatment and prevention efforts. This study investigated temporal changes in P. falciparum genetic diversity and MOI across three sites with varying malaria transmission intensities. Understanding these changes is essential for informing effective malaria control strategies for the different malaria transmission settings. Methods: A total of 220 P. falciparum-positive dried blood spot (DBS) filter paper samples from participants in a study conducted during 2011–2012 and 2015–2016 were analyzed. Genotyping utilized seven polymorphic markers: Poly-α, TA1, TA109, PfPK2, 2490, C2M34–313, and C3M69–383. Genetic diversity metrics, including the number of alleles and expected heterozygosity, were calculated using GENALEX and ARLEQUIN software. MOI was assessed by counting distinct genotypes. Multi-locus linkage disequilibrium (LD) and genetic differentiation were evaluated using the standardized index of association ( IAS) and Wright’s fixation index (FST), respectively. Statistical comparisons were made using the Kruskal–Wallis test, and temporal trends were analyzed using the Jonckheere–Terpstra test, with statistical significance set at p < 0.05. Results of the 220 samples, 180 were successfully amplified. The majority of participants were males (50.6%) and children aged 5–11 years (46.7%). Genetic diversity remained high, with mean expected heterozygosity (He) showing a slight decrease over time (range: 0.73–0.82). Polyclonal infections exceeded 50% at all sites, and mean MOI ranged from 1.7 to 2.2, with a significant reduction in Tororo (from 2.2 to 2.0, p = 0.03). Linkage disequilibrium showed a slight increase, with Kanungu exhibiting the lowest IAS in 2011–2012 (0.0085) and Jinja the highest (0.0239) in 2015–2016. Overall genetic differentiation remained low, with slight increases in pairwise FST values over time, notably between Jinja and Tororo (from 0.0145 to 0.0353). Conclusions: This study highlights the genetic diversity and MOI of P. falciparum in Uganda’s malaria transmission settings, noting a slight decrease in both genetic diversity and MOI over time. Continued surveillance and targeted control strategies are essential for monitoring the impact of malaria control efforts in Uganda.