NRU :: Browsing by Author "Mboowa, Gerald"

Browsing by Author "Mboowa, Gerald"

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An EarlyMorning Sputum Sample Is Necessary for the Diagnosis of Pulmonary Tuberculosis, Even withMore Sensitive Techniques: A Prospective Cohort Study among Adolescent TB-Suspects in Uganda
(Tuberculosis research and treatment, 2012-12-04) Ssengooba, Willy; Kateete, David P.; Mboowa, Gerald; Joloba, Moses L.
The World Health Organization (WHO) recommends collection of two sputum samples for tuberculosis (TB) diagnosis, with at least one being an early morning (EM) using smear microscopy. It remains unclear whether this is necessary even when sputum culture is employed. Here, we determined the diagnostic yield from spot and the incremental yield from the EM sputum sample cultures among TB-suspected adolescents from rural Uganda. Sputum samples (both spot and early-morning) from 1862 adolescents were cultured by the Lowenstein-Jensen (LJ) and Mycobacterium Growth Indicator Tube (MGIT) methods. For spot samples, the diagnostic yields for TB were 19.0% and 57.1% with LJ and MGIT, respectively, whereas the incremental yields (not totals) of the early-morning sample were 9.5% and 42.9% (P < 0.001) with LJ and MGIT, respectively. Among TB-suspected adolescents in rural Uganda, the EM sputum culture has a high incremental diagnostic yield. Therefore, EM sputum in addition to spot sample culture is necessary for improved TB case detection.
Bioinformatics mentorship in a resource limited setting
(Briefings in Bioinformatics, 2021) Jjingo, Daudi; Mboowa, Gerald; Sserwadda, Ivan; Kakaire, Robert; Kiberu, Davis; Amujal, Marion; Galiwango, Ronald; Kateete, David; Joloba, Moses; Whalen, Christopher C.
The two recent simultaneous developments of high-throughput sequencing and increased computational power have brought bioinformatics to the forefront as an important tool for effective and efficient biomedical research. Consequently, there have been multiple approaches to developing bioinformatics skills. In resource rich environments, it has been possible to develop and implement formal fully accredited graduate degree training programs in bioinformatics. In resource limited settings with a paucity of expert bioinformaticians, infrastructure and financial resources, the task has been approached by delivering short courses on bioinformatics—lasting only a few days to a couple of weeks. Alternatively, courses are offered online, usually over a period of a few months. These approaches are limited by both the lack of sustained in-person trainer–trainee interactions, which is a key part of quality mentorships and short durations which constrain the amount of learning that can be achieved.
CCR5 promoter variants among Ugandan HIV-1 elite and viremic controllers: a laboratory ฀ based cross ฀ sectional study
(Research Square, 2020) Nyiro, Brian; Amanya, Sharon B.; Nabatanzi, Rose; Bayiyana, Alice; Kalazane, Linda I.; Waswa, Francis; Nabulime, Eva; Karara, Daniel; Kabali, Joel; Mboowa, Gerald; Kayongo, Alex; Kateete, David P.; Nankya, Immaculate
Mechanisms for HIV control among HIV-1 elite and viremic-controllers are not fully understood. In Uganda, Studies have reported individuals who without Antiretroviral therapy have the inherent ability to control HIV progression to AIDS for a period of greater than 5 years. However, reasons for this phenotype are not understood. The study objective was to determine the distribution of CCR5 co-receptor on CD4+ T-cells and its associated promoter variants among HIV-1 elite and viremic-controllers. Methods We isolated CD4+T-cells from PBMCs using EasySep CD4+ T-cell negative selection kit, and stimulated them with anti-CD3 and anti-CD28 for 48 hours. To quantify CCR5 expression, we performed immune-phenotyping using flow cytometry. CCR5 promoter polymorphisms were determined through sanger sequencing. The Kruskal–Wallis and the Mann-Whitney test were used to compare differences in the percentages of CCR5+ CD4+ T-cells and the differences in CCR5 densities on CD4+ T-cells respectively. p values < 0.05 were considered significant. Results The percentage of CCR5+CD4+ T-cells was higher among the non-controllers compared to the controllers although, the difference was not statistically significant; elite and viremic-controllers (p=0.9173), viremic and non-controllers (0.0702), elite and non-controllers (0.6010). Of significance was the CCR5 densities on CD4+ T-cells, which were significantly higher among non-controllers relative to the controllers; elite and viremic-controllers (p=3048), viremic and non43 controllers (P=0.0312), elite and non-controllers (P=0.0210)
Clinico-pathological features of tuberculosis due to Mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study
(BMC clinical pathology, 2014-04-02) Wamala, Dan; Asiimwe, Benon; Mboowa, Gerald; Kallenius, Gunilla
Tuberculous lymphadenitis is next to pulmonary tuberculosis as the most common cause of tuberculosis. Uganda genotype, one of the sub-lineages of Mycobacterium tuberculosis, is the most prevalent cause of pulmonary tuberculosis in Uganda. We here investigate the clinicopathological characteristics of patients with tuberculous lymphadenitis infected with M. tuberculosis Uganda genotype compared with those infected with M. tuberculosis non-Uganda genotype strains. Between 2010 and 2012, we enrolled 121 patients (mean age 28.5 yrs, male 48%; female 52%) with tuberculous lymphadenitis, and categorized them by their M. tuberculosis genotypes. The clinical features and lymph node cytopathological parameters were compared between patients in the Uganda and non-Uganda categories using a crude and multivariable logistic regression model with adjustment for confounding factors. Of the 121participants, 56 (46%) were infected with strains of Uganda genotype. Patients infected with this genotype had significantly lower frequency of abdominal lymphadenopathy (odds ratio 0.4, p = 0.046) after adjusting for sex, age and HIV. Abdominal lymphadenopathy was also significantly associated with abnormal chest X-ray (p = 0.027). Tuberculous lymphadenitis patients infected with M. tuberculosis Uganda genotype were significantly less prone to have abdominal lymphadenopathy indicating potential reduced ability to disseminate and supporting the concept that differences in M. tuberculosis genotype may have clinical implications.
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, Mogomotsi
The 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 v
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.”
Delayed culture conversion predicts poor outcomes for isoniazid mono-resistant TB in Uganda: a retrospective cross-sectional study from 2017– 2022
(BioMed Central Ltd, 2025-07-01) Kabugo, Joel;; Sande, Obondo James;; Kabahita, Jupiter Marina ;; Namutebi, Joanita;; Mujuni, Dennis;; Oundo, Hellen Rosette;; Kisakye, Daniel;; Batte, Dorothy Nassozi;; Joloba, Moses;; Mboowa, Gerald
BackgroundIsoniazid-resistant, Rifampicin-susceptible Tuberculosis (TB) is estimated to occur in 13% of new cases and 17% of previously treated cases. Current WHO guidelines recommend treatment with Rifampicin (RFP), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (LFX, Q) for 6 months in patients with isoniazid mono-resistant TB (Hr-TB) but the effectiveness and use of other regimens in managing Hr-TB has not been established. There is a need to pay increased attention to the timely identification of Hr-TB patients to improve treatment success along with the reduction of the risk for further drug resistance development. This study was performed to determine the treatment outcomes and their associated factors among isoniazid mono-resistant TB patients in Uganda.MethodsThis was a cross-sectional study performed among newly diagnosed and retreatment TB patients whose sputum samples were referred to the National TB Reference Laboratory (NTRL)-Uganda from March 2017 to March 2022. Patient samples exhibiting Isoniazid mono-resistance as determined by phenotypic drug resistance testing (DST) were included in this study. Samples with data incompleteness and those whose treatment centers could not be traced were excluded from the study. Selected samples were tested for mutations associated with Isoniazid resistance using line probe. Patient demographic data was obtained from the National TB Reference Laboratory (NTRL) electronic data system and request forms with additional data, such as treatment regimen, adverse effects, and treatment start dates obtained from treatment registers. The independent variables available (age, sex, regimen used, M. tuberculosis mutation genes for isoniazid, specifically InhA and KatG, history of TB, HIV status, and reporting year) were assessed as possible factors in the relationship between Hr-TB and treatment success.ResultsA total of 85 isoniazid monoresistant isolates from different patients were analyzed in this study. In this study, most of the participants belonged to the category of newly diagnosed 35/85 (41.2%). Most of the participants 36/85, 42.3%) turned culture negative at month one upon initiation of treatment. The findings from this study show that the most dominant Mycobacterium tuberculosis mutation occurred in the KatG MUT1 region with a nucleotide change of S315T1. There was no significant treatment outcome difference among the different age groups in this study when compared (unsuccessful Vs successful treatment, median age 35.4 years and 35.86 years, p = 0.078). However, the study found that most deaths were among people aged above 36 years 71.4%, (5/7 participants).ConclusionThis study revealed Isoniazid mono-resistant TB as a significant factor associated with delayed culture conversion of beyond two (2) months. This emphasizes the need for prompt detection using routine point-of-care testing molecular diagnostic platforms to test for Isoniazid and Rifampicin resistance to improve TB treatment outcomes and reduce failures.Clinical trial numberNot applicable. Publicly Available Content Database
Feasibility Of Establishing A Biosafety Level 3 Tuberculosis Culture Laboratory Of Acceptable Quality Standards In A Resource-Limited Setting: An Experience From Uganda
(Health research policy and systems, 2015) Ssengooba, Willy; Gelderbloem, Sebastian J.; Mboowa, Gerald; Wajja, Anne; Namaganda, Carolyn; Musoke, Philippa; Kizza, Harriet Mayanja; Joloba, Moses Lutaakome
Despite the recent innovations in tuberculosis (TB) and multi-drug resistant TB (MDR-TB) diagnosis, culture remains vital for difficult-to-diagnose patients, baseline and end-point determination for novel vaccines and drug trials. Herein, we share our experience of establishing a BSL-3 culture facility in Uganda as well as 3-years performance indicators and post-TB vaccine trials (pioneer) and funding experience of sustaining such a facility.Between September 2008 and April 2009, the laboratory was set-up with financial support from external partners. After an initial procedure validation phase in parallel with the National TB Reference Laboratory (NTRL) and legal approvals, the laboratory registered for external quality assessment (EQA) from the NTRL, WHO, National Health Laboratories Services (NHLS), and the College of American Pathologists (CAP). The laboratory also instituted a functional quality management system (QMS). Pioneer funding ended in 2012 and the laboratory remained in self-sustainability mode.The laboratory achieved internationally acceptable standards in both structural and biosafety requirements. Of the 14 patient samples analyzed in the procedural validation phase, agreement for all tests with NTRL was 90% (P <0.01). It started full operations in October 2009 performing smear microscopy, culture, identification, and drug susceptibility testing (DST). The annual culture workload was 7,636, 10,242, and 2,712 inoculations for the years 2010, 2011, and 2012, respectively. Other performance indicators of TB culture laboratories were also monitored. Scores from EQA panels included smear microscopy >80% in all years from NTRL, CAP, and NHLS, and culture was 100% for CAP panels and above regional average scores for all years with NHLS. Quarterly DST scores from WHO-EQA ranged from 78% to 100% in 2010, 80% to 100% in 2011, and 90 to 100% in 2012.From our experience, it is feasible to set-up a BSL-3 TB culture laboratory with acceptable quality performance standards in resource-limited countries. With the demonstrated quality of work, the laboratory attracted more research groups and post-pioneer funding, which helped to ensure sustainability. The high skilled experts in this research laboratory also continue to provide an excellent resource for the needed national discussion of the laboratory and quality management systems.
Genetic Diversity of Bundibugyo Ebolavirus from Uganda and the Democratic Republic of Congo
(bioRxiv, 2021) Omara, Isaac Emmanuel; Kiwuwa-Muyingo, Sylvia; Balinandi, Stephen; Nyakarahuka, Luke; Kiconco, Jocelyn; Kayiwa, John Timothy; Mboowa, Gerald; Jjingo, Daudi; Lutwama, Julius J.
The Ebolavirus is one of the deadliest viral pathogens which was first discovered in the year 1976 during two consecutive outbreaks in the Democratic Republic of Congo and Sudan. Six known strains have been documented. The Bundibugyo Ebolavirus in particular first emerged in the year 2007 in Uganda. This outbreak was constituted with 116 human cases and 39 laboratory confirmed deaths. After 5 years, it re-emerged and caused an epidemic for the first time in the Democratic Republic of Congo in the year 2012 as reported by the WHO. Here, 36 human cases with 13 laboratory confirmed deaths were registered. Despite several research studies conducted in the past, there is still scarcity of knowledge available on the genetic diversity of Bundibugyo Ebolavirus. We undertook a research project to provide insights into the unique variants of Bundibugyo Ebolavirus that circulated in the two epidemics that occurred in Uganda and the Democratic Republic of Congo
Medical Mycology Dissertation Topics Require Prioritization among Postgraduate Microbiology trainees of Makerere University, Uganda
(IJID Regions, 2022) Achan, Beatrice; Mboowa, Gerald; Kwizera, Richard; Kajumbula, Henry; Kateete, David P.; Bongomin, Felix
As elsewhere worldwide, there is an increasing burden of fungal diseases in Uganda. However, expertise in medical mycology (the study of fungal diseases of medical importance) among clinicians and laboratory personnel remains low.This study sought to determine the proportion of dissertations on medical mycology among postgraduate medical microbiology trainees at the College of Health Sciences, Makerere University, Uganda.We retrospectively reviewed the topics of dissertations submitted to the Departments of Medical Microbiology and Immunology & Molecular Biology from 2011 through 2018. The proportion of dissertation topics on medical mycology was analysed using descriptive statistics.A total of 152 dissertations were retrieved. Of these, only 5 (3.3%) were on medical mycology compared to bacteriology (50.7%, n = 77), virology (27.6%, n = 42), parasitology (14.5%, n = 22) and immunology (4.0%, n = 6). Of the 5 dissertations on fungal diseases, the distribution was as follows: cryptococcal meningitis (40%, n = 2), Candidiasis (20%, n = 1), superficial mycoses (20%, n = 1) and other invasive fungal diseases (20%, n = 1). The most common method that was used for studying the fungal diseases was culture 60%, n = 3. There is limited research on medical mycology among the postgraduate medical microbiology trainees of Makerere University, Uganda.
Serological and molecular investigation for brucellosis in swine in selected districts of Uganda
(Tropical Animal Health and Production, 2016) Erume, Joseph; Roesel, Kristina; Dione, Michel M.; Ejobi, Francis; Mboowa, Gerald; Kungu, Joseph M.; Akol, Joyce; Pezo, Danilo; El-Adawy, Hosny; Melzer, Falk; Elschner, Mandy; Neubauer, Heinrich; Grace, Delia
Brucellosis is a notifiable zoonotic disease affecting livestock, humans, and wildlife in Uganda. Pigs can be infected with human pathogenic Brucella suis biovars 1 and 3 and can be a significant source of brucellosis for humans. Uganda has a rapidly growing pig population, and the pork consumption per capita is the highest in East Africa. The objective of this work was to determine the seroprevalence of brucellosis in Ugandan pigs. A cross-sectional serosurvey of pigs was conducted in three of the major pig-keeping districts in Uganda (Masaka (n= 381 samples), Mukono (n = 398), and Kamuli (n = 414)). In addition, pigs originating from these districts were sampled in the major pig abattoir in Kampala (n =472). In total, 1665 serum samples were investigated by serological and molecular tests. Only three putative brucellosis-positive samples were detected serologically using indirect ELISA. These sera were found negative for Brucella antibodies by CFT; however, two had antibodies against Yersinia enterocolitica as determined by SAT. Presence of antibodies against Yersiniae was confirmed by Y. enterocolitica antibody-specific ELISA. The two Yersiniae ELISA-positive samples were brucellosis negative using real-time PCR. We tested additional 142 sera from the 1665 samples with real-time PCR. All tested negative. Under this type of production system, we expect a maximum B. suis prevalence of less than 1 % at 95 % confidence level, and therefore, the risk of acquiring brucellosis from the pigs or their products is negligible. However, pigs may harbor the zoonotic Y. enterocolitica. This is the first study to investigate the occurrence of brucellosis in pigs in Uganda and the first study to report Y. enterocolitica antibodies in swine in Uganda.
Species And Genotypic Diversity Of Non-Tuberculous Mycobacteria Isolated From Children Investigated For Pulmonary Tuberculosis In Rural Uganda
(BMC infectious diseases, 2013) Asiimwe, Benon B.; Bagyenzi, Godwins B.; Ssengooba, Willy; Mumbowa, Francis; Mboowa, Gerald; Wajja, Anne; Kiiza, Harriet Mayanja; Musoke, Philippa M.; Wobudeya, Eric; Kallenius, Gunilla; Joloba, Moses L.
Smear microscopy, a mainstay of tuberculosis (TB) diagnosis in developing countries, cannot differentiate M. tuberculosis complex from NTM infection, while pulmonary TB shares clinical signs with NTM disease, causing clinical and diagnostic dilemmas. This study used molecular assays to identify species and assess genotypic diversity of non-tuberculous mycobacteria (NTM) isolates from children investigated for pulmonary tuberculosis at a demographic surveillance site in rural eastern Uganda. Children were investigated for pulmonary tuberculosis as part of a TB vaccine surveillance program (2009–2011). Two cohorts of 2500 BCG vaccinated infants and 7000 adolescents (12–18 years) were recruited and followed up for one to two years to determine incidence of tuberculosis. Induced sputum and gastric aspirates were processed by the standard N-acetyl L-cysteine (NALC)-NaOH method. Sediments were cultured in the automated MGIT (Becton Dickson) liquid culture system and incubated at 37°C for at least six weeks. Capilia TB assay was used to classify mycobacteria into MTC and NTM. The GenoType CM/AS assays were performed to identify species while Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR genotyping was used to assess genetic diversity of the strains within each species. Among 2859 infants and 2988 adolescents screened, the numbers of TB suspects were 710 and 1490 infants and adolescents respectively. The prevalence of NTM in infant suspects was 3.7% (26/710) (95% CI 2.5–5.2) while that in adolescent suspects was 4.6% (69/1490) (95% CI 3.6–5.8). On culture, 127 isolates were obtained, 103 of which were confirmed as mycobacteria comprising of 95 NTM and eight M. tuberculosis complex. The Genotype CM/AS assay identified 63 of the 95 NTM isolates while 32 remained un-identified. The identified NTM species were M. fortuitum (40 isolates, 63.5%), M. szulgai (9 isolates, 14.3%), M. gordonae (6 isolates, 9.5%), M. intracellulare (3 isolates, 4.7%), M. scrofulaceum (2 isolates, 3.2%), M. lentiflavum (2 isolates, 3.2%), and M. peregrinum (1 isolate, 1.6%). Genotyping did not reveal any clustering in M. intracellulare, M. gordonae and M. szulgai species. M. fortuitum, on the other hand, had two clusters, one with three isolates of M. fortuitum 1 and the other with two isolates of M. fortuitum 2 subspecies. The remaining 35 of the 40 isolates of M. fortuitum had unique fingerprint patterns.M. fortuitum is the most common cause of infection by NTM among Infants and adolescents in rural Uganda. There is a varied number of species and genotypes, with minimal clustering within species, suggesting ubiquitous sources of infection to individuals in this community.
The dawn of a cure for sickle cell disease through CRISPR-based treatment: A critical test of equity in public health genomics
(Annals of Human Genetics, 2024) Mboowa, Gerald; Sserwadda, Ivan; Kanyerezi, Stephen; Tukwasibwe, Stephen; Kidenya, Benson
Equity in access to genomic technologies, resources, and products remains a great challenge. This was evident especially during the coronavirus disease 2019 (COVID‐19) pandemic when the majority of lower middle‐income countries were unable to achieve at least 10% population vaccination coverage during initial COVID‐19 vaccine rollouts, despite the rapid development of those vaccines. Sickle cell disease (SCD) is an inherited monogenic red blood cell disorder that affects hemoglobin, the protein that carries oxygen through the body. Globally, the African continent carries the highest burden of SCD with at least 240,000 children born each year with the disease. SCD has evolved from a treatable to a curable disease. Recently, the UK medical regulator approved its cure through clustered regularly interspaced short palindromic repeat (CRISPR)‐based treatment, whereas the US Food and Drug Administration has equally approved two SCD gene therapies. This presents a remarkable opportunity to demonstrate equity in public health genomics. This CRISPR‐based treatment is expensive and therefore, a need for an ambitious action to ensure that they are affordable and accessible where they are needed most and stand to save millions of lives.
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.
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.

Browsing by Author "Mboowa, Gerald"

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