Browsing by Author "Baguma, Andrew"

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    Distribution of Candida species isolated from people living with human immunodeficiency virus with oropharyngeal and oral candidiasis in Africa in the era of universal test and treat policy: a systematic review and meta‑analysis
    (Springer Nature, 2024-11-27) Musinguzi, Benson; Obuku, Ekwaro A.; Mwesigwa, Alex; Migisha, Richard; Kinengyere, Alison Annet; Ndagire, Regina; Baguma, Andrew; Okek, Erick Jacob; Olum, Ronald; Itabangi, Herbert; Mboowa, Gerald; Sande, Obondo James; Achan, Beatrice
    Background: The introduction of antiretroviral therapy (ART) and the implementation of the human immunodeficiency virus (HIV) universal test and treat (UTT) policy have led to a decline in the incidence of opportunistic infections. However, oropharyngeal and oral candidiasis remain prevalent and continue to pose challenges among people living with human immunodeficiency virus (PLHIV) in Africa, indicating the need for a better understanding of the distribution of Candida species responsible for these infections. This systematic review and meta-analysis aimed to determine the distribution of Candida species isolated from PLHIV with oropharyngeal and oral candidiasis in Africa in the era of UTT policy. Methods: The review followed the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. A comprehensive search was conducted to identify eligible studies to be included in the meta-analysis and analysed using a random effects model in STATA version 17. The risk of bias was assessed using the Joanna Briggs Institute quality assessment tool. Results: Fourteen studies with 4281 participants were included in the review. Overall, 2095 Candida isolates were reported, 78.7% (1650/2095) of which were C. albicans, 19.6% (410/2095), non-albicans Candida (NAC), and 1.7% (35/2095) could not be identified to the Candida specific species level. The most prevalent NAC species were C. glabrata (26.3%), followed by C. tropicalis (24.9%), C. krusei (15.6%), C. parapsilosis (11%), and C. dubliniensis (6.3%). The pooled prevalence of oropharyngeal and oral candidiasis was 48% (95% CI 34–62%). The prevalence of oropharyngeal candidiasis was higher in the pre-UTT era, at 56% (95% CI 40–72%, p < 0.001), than in the post-UTT era, at 34% (95% CI 10–67%, p < 0.001). The risk of bias assessment revealed that 71.4% (10/14) of the included studies had a low risk of bias and that 28.6% (4/14) had a moderate risk of bias. Conclusions: While C. albicans remain, the predominant species causing oropharyngeal and oral candidiasis among PLHIV in Africa, NAC species also contribute significantly to the infection burden. Despite ART and UTT policies, oropharyngeal candidiasis remains prevalent, emphasizing the need for targeted interventions.
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    Investigating metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections: protocol for a laboratory-based cross-sectional study
    (JMIR Publications, 2023-04-09) Njovu, Israel Kiiza; Nalumaga, Pauline Petra; Ampaire, Lucas; Nuwagira, Edwin; Mwesigye, James; Musinguzi, Benson; Kassaza, Kennedy; Taseera, Kabanda; Mukasa, James Kiguli; Bazira, Joel; Iramiot, Jacob Stanley; Baguma, Andrew; Bongomin, Felix; Kwizera, Richard; Achan, Beatrice; Cox, Michael J; King, Jason S; May, Robin; Ballou, Elizabeth R; Itabangi, Herbert
    Background: Fungal-bacterial cocolonization and coinfections pose an emerging challenge among patients suspected of having pulmonary tuberculosis (PTB); however, the underlying pathogenic mechanisms and microbiome interactions are poorly understood. Understanding how environmental microbes, such as fungi and bacteria, coevolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic pulmonary fungal coinfections. In this project, we propose to study the coexistence of fungal and bacterial microbial communities during chronic pulmonary diseases, with a keen interest in underpinning fungal etiological evolution and the predominating interactions that may exist between fungi and bacteria. Objective: This is a protocol for a study aimed at investigating the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections through determining and characterizing the burden, etiological profiles, microbial communities, and interactions established between fungi and bacteria as implicated among patients with presumptive PTB. Methods: This will be a laboratory-based cross-sectional study, with a sample size of 406 participants. From each participant, 2 sputa samples (one on-spot and one early morning) will be collected. These samples will then be analyzed for both fungal and bacterial etiology using conventional metabolic and molecular (intergenic transcribed spacer and 16S ribosomal DNA–based polymerase chain reaction) approaches. We will also attempt to design a genome-scale metabolic model for pulmonary microbial communities to analyze the composition of the entire microbiome (ie, fungi and bacteria) and investigate host-microbial interactions under different patient conditions. This analysis will be based on the interplays of genes (identified by metagenomics) and inferred from amplicon data and metabolites (identified by metabolomics) by analyzing the full data set and using specific computational tools. We will also collect baseline data, including demographic and clinical history, using a patient-reported questionnaire. Altogether, this approach will contribute to a diagnostic-based observational study. The primary outcome will be the overall fungal and bacterial diagnostic profile of the study participants. Other diagnostic factors associated with the etiological profile, such as incidence and prevalence, will also be analyzed using univariate and multivariate schemes. Odds ratios with 95% CIs will be presented with a statistical significance set at P<.05. Results: The study has been approved by the Mbarara University Research Ethic Committee (MUREC1/7-07/09/20) and the Uganda National Council of Science and Technology (HS1233ES). Following careful scrutiny, the protocol was designed to enable patient enrollment, which began in March 2022 at Mbarara University Teaching Hospital. Data collection is ongoing and is expected to be completed by August 2023, and manuscripts will be submitted for publication thereafter. Conclusions: Through this protocol, we will explore the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections among patients with presumptive PTB. Establishing key fungal-bacterial cross-kingdom synergistic relationships is crucial for instituting fungal bacterial coinfecting etiology.
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    Laboratory diagnosis of candidiasis
    (IntechOpen, 2022-08-04) Musinguzi, Benson; Sande, Obondo J.; Mboowa, Gerald; Baguma, Andrew; Itabangi, Herbert; Achan, Beatrice
    The burden of Candidiasis continues to increase and so does the Candida species. Although Candida species are closely similar phenotypically, they differ from each other in terms of epidemiology, genetic characteristics, antifungal susceptibility and virulence profile. Therefore, reliable and accurate laboratory methods for identification of Candida species can determine the Candidiasis burden and enable the administration of the most appropriate antifungal drug therapy to reduce fungal mortality rates. Conventional and biochemical methods are often used in identification of Candida species. However, these techniques are specific and sensitive enough in detecting the non albicans candida (NAC) species. Molecular techniques have improved the laboratory diagnosis and management of Candidiasis due to improved sensitivity and specificity threshold. This chapter provides an overview of different laboratory methods for diagnosis of Candidiasis.
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    Temporal changes in Plasmodium falciparum genetic diversity and multiplicity of infection across three areas of varying malaria transmission intensities in Uganda
    (Springer Nature, 2023-12-30) 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 of 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 weremade 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 IA S 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).