Browsing by Author "Wayengera, Misaki"
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Item Adipose-derived stromal vascular fraction (SVF) in scar treatment: a systematic review protocol(American Journal of Stem Cells, 2022) Mbiine, Ronald; Wayengera, Misaki; Ocan, Moses; Kiwanuka, Noah; Munabi, Ian; Muwonge, Haruna; Lekuya, Hervé Monka; Kawooya2, Ismael Cephas Nakanwagi3,4, Alison Annet Kinengyere; Joloba, Moses; Galukande, MosesAutologous adipose-derived stromal vascular fraction (SVF) is an emerging therapy that is being pioneered as a potential treatment for keloids and hypertrophic scars. Up to this point, there isn’t a cure for keloids and hypertrophic scars yet they comprise the commonest benign skin disorders. Despite published studies reporting potential therapeutic benefits of SVF, their use and efficacy on scar improvement are not clearly described. The aim of this review is to describe the clinical practice involved in harvesting, processing, utilization of SVF, and associated efficacy in scar treatment. Methods: We shall include published clinical articles evaluating the efficacy of SVF on improving scar characteristics and assessment scores among adults with keloids or hypertrophic scars. Article search of Medline/PubMed, Cochrane Library and Embase using Mesh terms of “scars” and “stromal vascular fraction” combined with the Boolean operators (“AND”, “OR”) will be performed by two independent researchers following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. The primary outcome measure will be the mean difference in the Scar characteristics including Scar assessment scores, scar thickness among others. Data synthesis: Descriptive data synthesis and mean differences between treatment arms will be calculated for the primary outcome of the scar assessment scores. In case more than three studies provide consistent characteristics of the scar assessment scores, a meta-analysis will be conducted. Discussion: Evidence obtained from the systematic review will form the foundation upon which further clinical trials research will be conducted in evaluating the efficacy of autologous adipose-derived stromal vascular fraction in keloid and hypertrophic scar. The systematic review has been submitted to the PROSPERO database and is currently under review.Item The Collaborative African Genomics Network (CAfGEN): Applying Genomic technologies to probe host factors important to the progression of HIV and HIV-tuberculosis infection in sub-Saharan Africa [version 1; referees: awaiting peer review](AAS open research, 2018) Mboowa, Gerald; Mwesigwa, Savannah; Katagirya, Eric; Retshabile, Gaone; Mlotshwa, Busisiwe C.; Williams, Lesedi; Kekitiinwa, Adeodata; Kateete, David; Wampande, Eddie; Wayengera, Misaki; Nsangi Kintu, Betty; Kisitu, Grace P.; Kyobe, Samuel; Brown, Chester W.; Hanchard, Neil A.; Mardon, Graeme; Joloba, Moses; Anabwani, Gabriel; Pettitt, Ed; Tsimako-Johnstone, Masego; Kasvosve, Ishmael; Maplanka, Koketso; Mpoloka, Sununguko W.; Hlatshwayo, Makhosazana; Matshaba, MogomotsiThe Human Heredity and Health in Africa consortium (H3Africa) was conceived to facilitate the application of genomics technologies to improve health across Africa. Here, we describe how the Collaborative African Genomics Network (CAfGEN) of the H3Africa consortium is using genomics to probe host genetic factors important to the progression of HIV and HIV-tuberculosis (TB) coinfection in sub-Saharan Africa. Methods: CAfGEN is an H3Africa collaborative centre comprising expertise from the University of Botswana; Makerere University; Baylor College of vItem The collaborative African genomics network training program: a trainee perspective on training the next generation of African scientists(Genetics in Medicine, 2017) Mlotshwa, Busisiwe C.; Mwesigwa, Savannah; Mboowa, Gerald; Williams, Lesedi; Retshabile, Gaone; Kekitiinwa, Adeodata; Wayengera, Misaki; Kyobe, Samuel; Brown, Chester W.; Hanchard, Neil A.; Mardon, Graeme; Joloba, Moses; Anabwani, Gabriel; Mpoloka, Sununguko W.The Collaborative African Genomics Network (CAf- GEN) aims to establish sustainable genomics research programs in Botswana and Uganda through long-term training of PhD students from these countries at Baylor College of Medicine. Here, we present an overview of the CAfGEN PhD training program alongside trainees’ perspectives on their involvement. Background: Historically, collaborations between high-income countries (HICs) and low- and middle-income countries (LMICs), or North–South collaborations, have been criticized for the lack of a mutually beneficial distribution of resources and research findings, often undermining LMICs. CAfGEN plans to address this imbalance in the genomics field through a program of technology and expertise transfer to the participating LMICs. Methods: An overview of the training program is presented. Trainees from the CAfGEN project summarized their experiences, looking specifically at the training model, benefits of the program, challenges encountered relating to the cultural transition, and program outcomes after the first 2 years. Conclusion: Collaborative training programs like CAfGEN will not only help establish sustainable long-term research initiatives in LMICs but also foster stronger North–South and South–South networks. The CAfGEN model offers a framework for the development of training programs aimed at genomics education for those for whom genomics is not their “first language.”Item A Cross Sectional Study on Knowledge and Attitudes About Organ Donation and Transplantation in an Urban Population in a Low-Income Country(Research Square, 2023) Kituuka, Olivia; Ocan, Moses; Mbiine, Ronald; Ibingira, Charles; Wayengera, Misaki; Tayebwa, MordecaiUganda’s Health Sector Development Plan (2015/16 -2019/2020) noted that most referrals for treatment abroad were for organ transplant services costing government over 5.6 million US dollars. The government of Uganda has invested in building capacity for Organ donation and transplantation services by training human resource and setting up the infrastructure in Kampala where these services can be accessed. However, there is no information on the readiness of communities and the scientific community to embrace (communities) or undertake (science) organ transplantation in the country. We set out to assess Knowledge and Attitudes about organ donation and transplantation among the urban population in Kampala. Methods: We conducted a cross-sectional survey among 395 participants from the urban population of Kampala at Garden City Mall, Wandegeya market and Nakawa market 28th May - 7th June 2021. We asked about knowledge about organ donation and transplantation, collected sociodemographic data and did a sentiment analysis of participants' attitudes towards organ donation and transplantation. Results: The M:F ratio of participants was 1:1, majority (55.9%) of participants were Baganda, two thirds of participants knew about organ donation, 90% of participants did not know of any government policy on organ donation and transplantation. Radio/television was the commonest source of information. The commonest organ donated was the kidney. Overall, there were 94.3% and 93.2% positive sentiments towards organ transplantation and organ donation respectively. The need for stricter laws governing organ donation and transplantation, corruption and fear were the main negative sentiments expressed by participants. Conclusions: Sensitization of the community is required about government policy on organ donation and transplantation, and this should be communicated through radio/television and social media. There was a positive attitude towards organ donation and transplantation.Item Emphasizing the vitality of genomics related research in the area of infectious diseases(Scientific Research and Essays, 2007) Wayengera, Misaki; Byarugaba, WilsonSequencing of the human and other species genomes has generated a downstream of sciences that have taken advantage of this knowledge to generate vital links between diseases and genetic variants. Sub-Saharan Africa and many developing countries form the major epicenters for Infectious diseases. Here, the role that genomics may hold in the area of infectious diseases research is emphasized in five blocks: phenotype evaluation studies, evolutionary trends’ studies across microbial and host genomes, idiopathic association or host susceptibility studies to disease, therapeutics or vaccine research insights, as well as the development of novel molecular diagnostics.Item Exome Sequencing Reveals a Putative Role for HLA-C*03:02 in Control of HIV-1 in African Pediatric Populations(Frontiers in Genetics, 2021) Kyobe, Samuel; Mwesigwa, Savannah; Kisitu, Grace P.; Farirai, John; Katagirya, Eric; Mirembe, Angella N.; Ketumile, Lesego; Wayengera, Misaki; Ashaba Katabazi, Fred; Kigozi, Edgar; Wampande, Edward M.; Retshabile, Gaone; Mlotshwa, Busisiwe C.; Williams, Lesedi; Morapedi, Koketso; Kasvosve, Ishmael; Kyosiimire-Lugemwa, Jacqueline; Nsangi, Betty; Tsimako-Johnstone, Masego; Brown, Chester W.; Joloba, Moses; Anabwani, Gabriel; Bhekumusa, Lukhele; Mpoloka, Sununguko W.; Mardon, Graeme; Matshaba, Mogomotsi; Kekitiinwa, Adeodata; Hanchard, Neil A.Human leucocyte antigen (HLA) class I molecules present endogenously processed antigens to T-cells and have been linked to differences in HIV-1 disease progression. HLA allelotypes show considerable geographical and inter-individual variation, as does the rate of progression of HIV-1 disease, with long-term non-progression (LTNP) of disease having most evidence of an underlying genetic contribution. However, most genetic analyses of LTNP have occurred in adults of European ancestry, limiting the potential transferability of observed associations to diverse populations who carry the burden of disease. This is particularly true of HIV-1 infected children. Here, using exome sequencing (ES) to infer HLA allelotypes, we determine associations with HIV- 1 LTNP in two diverse African pediatric populations. We performed a case-control association study of 394 LTNPs and 420 rapid progressors retrospectively identified from electronic medical records of pediatric HIV-1 populations in Uganda and Botswana. We utilized high-depth ES to perform high-resolution HLA allelotyping and assessed evidence of association between HLA class I alleles and LTNP. Sixteen HLA alleles and haplotypes had significantly different frequencies between Uganda and Botswana, with allelic differences being more prominent in HLA-A compared to HLA-B and C allelotypes. Three HLA allelotypes showed association with LTNP, including a novel association in HLA-C (HLA-B 57:03, aOR 3.21, Pc = 0.0259; B 58:01, aOR 1.89, Pc = 0.033; C 03:02, aOR 4.74, Pc = 0.033). Together, these alleles convey an estimated population attributable risk (PAR) of non-progression of 16.5%. We also observed novel haplotype associations with HLA-B 57:03-C 07:01 (aOR 5.40, Pc = 0.025) and HLA-B 58:01- C 03:02 (aOR 4.88, Pc = 0.011) with a PAR of 9.8%, as well as a previously unreported independent additive effect and heterozygote advantage of HLA-C 03:02 with B 58:01 (aOR 4.15, Pc = 0.005) that appears to limit disease progression, despite weak LD (r2 = 0.18) between these alleles. These associations remained irrespective of gender or country. In one of the largest studies of HIV in Africa, we find evidence of a protective effect of canonical HLA-B alleles and a novel HLA-C association that appears to augment existing HIV-1 control alleles in pediatric populations. Our findings outline the value of using multi-ethnic populations in genetic studies and offer a novel HIV-1 association of relevance to ongoing vaccine studies.Item Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and other SIV gene sequence cleavage by various bacteria restriction enzymes: Precursors for a novel HIV inhibitory product(African Journal of Biotechnology, 2007) Wayengera, Misaki; Wilson, Byarugaba; Henry, KajjumbulaResistance, toxicity and virologic failure have underlined the need to develop new HIV inhibitory products. Base on the natural bacteria “restriction modification system” antiviral immune model, we set out to analyze the effects of various restriction enzymes on the HIV genome. A computer simulated model using Web cutter Version 2.0, and cytogenetic analysis. 339 restriction enzymes from Promega database, 10 HIV-1/SIVcpz genes, 10 HIV-2/SIVsmm genes and 10 other SIV genes. Gene sequences were fed into Web cutter 2.0 set to search enzymes with at least 6 recognition base pairs (palindromes). A background in vitro cytogenetic control analysis using HIV-1/SIVcpz GAG, POL and ENV genes was done. Of the 339 enzymes used, 238 (70.2%) cleaved the HIV-1/SIVcpz A1.BY.97.97BL006_AF193275 genome with 9037 bp compared to 225 (66.4%) and 219 (64.6%) for the HIV-2/SIVsmm genome (9713 bp) and other SIV B.FR.83.HXB2_LAI_IIIB_BRU_K03455 genome (9719 bp), respectively. Individual genes had differing but potent susceptibility to the enzymes, with a 98.9% Web cutter PPV (95%CI, 97.2%- 99.6%) for in vitro cytogenetics. The natural bacteria RMS antiviral immune model offers precursors for developing novel HIV and other viral therapeutic molecules.Item Harnessing Pharmacogenomics to Tackle Resistance to the “Nucleoside Reverse Trancripatse Inhibitor” Backbone of Highly Active Antiretroviral Therapy in Resource Limited Settings(The open AIDS journal, 2008) Wayengera, Misaki; Kajumbula, Henry; Byarugaba, WilsonThe highest burden of the human immunodeficiency virus (HIV) epidemic is concentrated in the sub-Saharan region. Over 70% of all global HIV infections have been found to occur here [1]. Despite the earlier policy and patent controversies surrounding the use of highly active antiretroviral therapy (HAART) within this setting, HAART has widely gained application here [2]. This access to HAART can be mainly attributed to several advocacy and funding avenues [2-4]. Specifically, the World Bank and its global partners, in particular, with commitment by the G8, have ensured that several countries within this setting can meet the WHO 3’by 5” target of treating 3 million by 2005 [3,4].Item Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: inherent potential for biosynthetic versus live recombinant microbicides(Theoretical Biology and Medical Modeling, 2008) Wayengera, Misaki; Kajumbula, Henry; Byarugaba, WilsonHerpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of ~120–200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endonucleases (REases) with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2.Item In silico evidence for the species-specific conservation of mosquito retroposons: implications as a molecular biomarker(Theoretical Biology and Medical Modelling, 2009) Byarugaba, Wilson; Kajumbula, Henry; Wayengera, MisakiMosquitoes are the transmissive vectors for several infectious pathogens that affect man. However, the control of mosquitoes through insecticide and pesticide spraying has proved difficult in the past. We hypothesized that, by virtue of their reported vertical inheritance among mosquitoes, group II introns – a class of small coding ribonucleic acids (scRNAs) – may form a potential species-specific biomarker. Structurally, introns are a six-moiety complex. Depending on the function of the protein encoded within the IV moiety, the highly mobile class of group II introns or retroposons is sub-divided into two: Restriction Endonuclease (REase)-like and Apurinic aPyramydinic Endonuclease (APE)-like. REase-like retroposons are thought to be the ancestors of APE retroposons. Our aim in this study was to find evidence for the highly species-specific conservation of the APE subclass of mosquito retroposons.Item Safety and efficacy of hydroxychloroquine for treatment of non‑severe COVID‑19 among adults in Uganda: a randomized open label phase II clinical trial(BMC Infectious Diseases, 2021) Byakika‑Kibwika, Pauline; Sekaggya‑Wiltshire, Christine; Semakula, Jerome Roy; Nakibuuka, Jane; Musaazi, Joseph; Kayima, James; Sendagire, Cornelius; Meya, David; Kirenga, Bruce; Nanzigu, Sarah; Kwizera, Arthur; Nakwagala, Fred; Kisuule, Ivan; Wayengera, Misaki; Mwebesa, Henry G.; Kamya, Moses R.; Bazeyo, WilliamSeveral repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design: We conducted a randomized open label Phase II clinical trial from October–December 2020. Methods: Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6.Item Safety and feasibility of autologous adipose-derived stromal vascular fraction in the treatment of keloids: a phase one randomized controlled pilot trial(American Journal of Stem Cells, 2023) Mbiine, Ronald; Kayiira, Anthony; Wayengera, Misaki; Guyton, Munabi Ian; Kiwanuka, Noah; Alenyo, Rose; Wamala Kalanzi, Edris; Muwonge, Haruna; Nakanwagi, Cephas; Joloba, Moses; Galukande, MosesAutologous adipose-derived stromal vascular fraction (SVF) has been described to have therapeutic benefits in the treatment of keloids. However, most of the evidence on its efficacy is based on observational studies the majority of which are conducted in high-income countries and yet the highest burden of keloids is in low- and middle-income countries (LMICs). Objectives: We set out to determine the safety and feasibility of using autologous adipose derived stromal vascular fraction in the treatment of keloids in LMICs. Methods: In this phase II randomized controlled pilot clinical trial conducted in the Plastic Surgery Unit of Kirruddu National Referral Hospital in Kampala Uganda, 8 patients were assigned a 1:1 ratio to either SVF or triamcinolone acetonide (TAC) arms. In the SVF arm, a median (Inter quartile range) amount of stromal cell infiltration of 2.7×106 (11×106) was administered, while the controls received 10 mg/ml TAC at a ratio of 1:1 TAC to keloid volume. Primary endpoints were adverse event development based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 tool and feasibility assessment based on ≥ 70% recruitment feasibility and ≥ 80% interventional feasibility rates. Results: The participants’ mean age was 27.9 (±6.5) years, with a female predilection of 5 (63%). Overall, no adverse events were reported in the SVF arm, while ulceration in a single patient in the TAC arm, which was a grade II adverse event, was reported. Recruitment feasibility of 80% and interventional feasibility with 100% completion were reported. Conclusion: Based on our findings, an autologous adipose-derived stromal vascular fraction is feasible and safe for the treatment of keloids in LMICs.Item Targeting wild-type Erythrocyte receptors for Plasmodium falciparum and vivax Merozoites by Zinc Finger Nucleases In- silico: Towards a Genetic Vaccine against Malaria(Genetic Vaccines and Therapy, 2012) Kajumbula, Henry; Byarugaba, Wilson; Wayengera, MisakiMalaria causes immense human morbidity and mortality globally. The plasmodium species vivax and falciparum cause over 75 % clinical malaria cases. Until now, gene-based strategies against malaria have only been applied to plasmodium species and their mosquito-vector. Merozoites of these two respective plasmodium species target and invade red blood cells (RBCs) by using the duffy antigen receptor for chemokines (DARC), and Sialic Acid (SLC4A1) residues of the O-linked glycans of Glycophorin A. RBCs of naturally selected duffy-negative blacks are resistant to P.vivax tropism. We hypothesized that artificial aberration of the host-pathway by target mutagenesis of either RBC –receptors, may abolish or reduce susceptibility of the host to malaria. As a first step towards the experimental actualization of these concepts, we aimed to identify zinc finger arrays (ZFAs) for constructing ZFNs that target genes of either wild-type host-RBC- receptors.Item Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression(NPJ Genomic Medicine, 2021) Mwesigwa, Savannah; Williams, Lesedi; Retshabile, Gaone; Katagirya, Eric; Mboowa, Gerald; Mlotshwa, Busisiwe; Kyobe, Samuel; Kateete, David P.; Mujjwiga Wampande, Eddie; Wayengera, Misaki; Wata Mpoloka, Sununguko; Mirembe, Angella N.; Kasvosve, Ishmael; Morapedi, Koketso; Kisitu, Grace P.; Kekitiinwa, Adeodata R.; Anabwani, Gabriel; Joloba, Moses L.; Matovu, Enock; Mulindwa, Julius; Noyes, Harry; Botha, Gerrit; Brown, Chester W.; Mardon, Graeme; Matshaba, Mogomotsi; Hanchard, Neil A.Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%; p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), with Anelloviridae showing strong association with LTNP status (p = 3 × 10−4; q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02; q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of the Anelloviridae reads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.Item Whole-Exome Sequencing Reveals Uncaptured Variation and Distinct Ancestry in the Southern African Population of Botswana(The American Journal of Human Genetics, 2018) Retshabile, Gaone; Mlotshwa, Busisiwe C.; Williams, Lesedi; Mwesigwa, Savannah; Mboowa, Gerald; Huang, Zhuoyi; Rustagi, Navin; Swaminathan, Shanker; Katagirya, Eric; Kyobe, Samuel; Wayengera, Misaki; Kisitu, Grace P.; Kateete, David P.; Wampande, Eddie M.; Maplanka, Koketso; Kasvosve, Ishmael; Pettitt, Edward D.; Matshaba, Mogomotsi; Nsangi, Betty; Marape, Marape; Tsimako-Johnstone, Masego; Brown, Chester W.; Yu, Fuli; Kekitiinwa, Adeodata; Joloba, Moses; Mpoloka, Sununguko W.; Mardon, Graeme; Anabwani, Gabriel; Hanchard, Neil A.Large-scale, population-based genomic studies have provided a context for modern medical genetics. Among such studies, however, African populations have remained relatively underrepresented. The breadth of genetic diversity across the African continent argues for an exploration of local genomic context to facilitate burgeoning disease mapping studies in Africa.We sought to characterize genetic variation and to assess population substructure within a cohort of HIV-positive children from Botswana—a Southern African country that is regionally underrepresented in genomic databases. Using whole-exome sequencing data from 164 Batswana and comparisons with 150 similarly sequenced HIV-positive Ugandan children, we found that 13%–25% of variation observed among Batswana was not captured by public databases. Uncaptured variants were significantly enriched (p ¼ 2.2 3 10 16) for coding variants with minor allele frequencies between 1% and 5% and included predicted-damaging non-synonymous variants. Among variants found in public databases, corresponding allele frequencies varied widely, with Botswana having significantly higher allele frequencies among rare (<1%) pathogenic and damaging variants. Batswana clustered with other Southern African populations, but distinctly from 1000 Genomes African populations, and had limited evidence for admixture with extra-continental ancestries. We also observed a surprising lack of genetic substructure in Botswana, despite multiple tribal ethnicities and language groups, alongside a higher degree of relatedness than purported founder populations from the 1000 Genomes project. Our observations reveal a complex, but distinct, ancestral history and genomic architecture among Batswana and suggest that disease mapping within similar Southern African populations will require a deeper repository of genetic variation and allelic dependencies than presently exists.