Browsing by Author "Kateete, David Patrick"
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Item Acute Hypoxaemic Respiratory Failure In A Low-Income Country: A Prospective Observational Study Of Hospital Prevalence And Mortality(BMJ Open Respiratory Research, 2020) Kwizera, Arthur; Nakibuuka, Jane; Nakiyingi, Lydia; Sendagire, Cornelius; Tumukunde, Janat; Katabira, Catherine; Ssenyonga, Ronald; Kiwanuka, Noah; Kateete, David Patrick; Joloba, Moses; Kabatoro, Daphne; Atwine, Diana; Summers, CharlotteLimited data exist on the epidemiology of acute hypoxaemic respiratory failure (AHRF) in low-income countries (LICs). We sought to determine the prevalence of AHRF in critically ill adult patients admitted to a Ugandan tertiary referral hospital; determine clinical and treatment characteristics as well as assess factors associated with mortality.We conducted a prospective observational study at the Mulago National Referral and Teaching Hospital in Uganda. Critically ill adults who were hospitalised at the emergency department and met the criteria for AHRF (acute shortness of breath for less than a week) were enrolled and followed up for 90 days. Multivariable analyses were conducted to determine the risk factors for death.A total of 7300 patients was screened. Of these, 327 (4.5%) presented with AHRF. The majority (60 %) was male and the median age was 38 years (IQR 27–52). The mean plethysmographic oxygen saturation (SpO2) was 77.6% (SD 12.7); mean SpO2/FiO2 ratio 194 (SD 32) and the mean Lung Injury Prediction Score (LIPS) 6.7 (SD 0.8). Pneumonia (80%) was the most common diagnosis. Only 6% of the patients received mechanical ventilatory support. In-hospital mortality was 77% with an average length of hospital stay of 9.2 days (SD 7). At 90 days after enrolment, the mortality increased to 85%. Factors associated with mortality were severity of hypoxaemia (risk ratio (RR) 1.29 (95% CI 1.15 to 1.54), p=0.01); a high LIPS (RR 1.79 (95% CI 1.79 1.14 to 2.83), p=0.01); thrombocytopenia (RR 1.23 (95% CI 1.11 to 1.38), p=0.01); anaemia (RR 1.15 (95% CI 1.01 to 1.31), p=0.03) ; HIV co-infection (RR 0.84 (95% CI 0.72 to 0.97), p=0.019) and male gender (RR 1.15 (95% CI 1.01 to 1.31) p=0.04).The prevalence of AHRF among emergency department patients in a tertiary hospital in an LIC was low but was associated with very high mortality. Pneumonia was the most common cause of AHRF. Mortality was associated with higher severity of hypoxaemia, high LIPS, anaemia, HIV co-infection, thrombocytopenia and being male.Item Air pollution and mobility patterns in two Ugandan cities during COVID‑19 mobility restrictions suggest the validity of air quality data as a measure for human mobility(Environmental Science and Pollution Research, 2022) Galiwango, Ronald; Bainomugisha, Engineer; Kivunike, Florence; Kateete, David Patrick; Jjingo, DaudiWe explored the viability of using air quality as an alternative to aggregated location data from mobile phones in the two most populated cities in Uganda. We accessed air quality and Google mobility data collected from 15th February 2020 to 10th June 2021 and augmented them with mobility restrictions implemented during the COVID-19 lockdown. We determined whether air quality data depicted similar patterns to mobility data before, during, and after the lockdown and determined associations between air quality and mobility by computing Pearson correlation coefficients ( R ), conducting multivariable regression with associated confidence intervals (CIs), and visualized the relationships using scatter plots. Residential mobility increased with the stringency of restrictions while both non-residential mobility and air pollution decreased with the stringency of restrictions. In Kampala, PM2.5 was positively correlated with non-residential mobility and negatively correlated with residential mobility. Only correlations between PM2.5 and movement in work and residential places were statistically significant in Wakiso. After controlling for stringency in restrictions, air quality in Kampala was independently correlated with movement in retail and recreation (− 0.55; 95% CI = − 1.01– − 0.10), parks (0.29; 95% CI = 0.03–0.54), transit stations (0.29; 95% CI = 0.16–0.42), work (− 0.25; 95% CI = − 0.43– − 0.08), and residential places (− 1.02; 95% CI = − 1.4– − 0.64). For Wakiso, only the correlation between air quality and residential mobility was statistically significant (− 0.99; 95% CI = − 1.34– − 0.65). These findings suggest that air quality is linked to mobility and thus could be used by public health programs in monitoring movement patterns and the spread of infectious diseases without compromising on individuals’ privacy.Item Airway microbiome signature accurately discriminates Mycobacterium tuberculosis infection status(Elsevier Inc, 2024-06) Kayongo, Alex; Ntayi, Moses Levi; Olweny, Geoffrey; Kyalo, Edward; Ndawula, Josephine; Ssengooba, Willy; Kigozi, Edgar; Kalyesubula, Robert; Munana, Richard; Namaganda, Jesca; Caroline, Musiime; Sekibira, Rogers; Bagaya, Bernard Sentalo; Kateete, David Patrick; Joloba, Moses Lutaakome; Jjingo, Daudi; Sande, Obondo James; Mayanja-Kizza, HarrietAbstract Mycobacterium tuberculosis remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of M.tb infection and M.tb-specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. M.tb rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising Streptococcus, Neisseria, Fusobacterium, Prevotella, Schaalia, Actinomyces, Cutibacterium, Brevibacillus, Microbacterium, and Beijerinckiacea accurately discriminated active TB from Latent TB and M.tb-uninfected individuals. [Display omitted] •M.tb infection drives a significant reduction in airway microbiome diversity•M.tb-specific IFNg does not directly impact airway microbiome diversity•Airway microbiome signature discriminates active TB from LTBI and uninfected states•LTBI and M.tb-uninfected states display similar airway microbiome diversity Microbiology; Bacteriology; MicrobiomeItem Application of antibodies to recombinant heat shock protein 70 in immunohistochemical diagnosis of mycobacterium avium subspecies paratuberculosis in tissues of naturally infected cattle(Irish veterinary journal, 2017) Okuni, Julius Boniface; Kateete, David Patrick; Okee, Moses; Nanteza, Anna; Joloba, Moses; Ojok, LonzyDetection of Mycobacterium avium subspecies paratuberculosis (MAP) infection is key to the control of Johne’s disease. Immunohistochemistry is one of the methods of detection of MAP infection in tissues. However, unavailability of commercial antibodies that can detect the organism is a limiting factor for the use of immunohistochemistry. This study was aimed at developing an immunohistochemistry method to diagnose MAP in infected tissues using antibodies against MAP recombinant heat shock protein 70kd.MAP Heat shock protein 70 gene was amplified and cloned into an expression vector, Champion pET-SUMO, then expressed in E coli, purified and used to produce polyclonal rabbit antibodies against the Heat shock protein. Immunohistochemistry was performed in 35 MAP infected tissues with anti-HSP70 polyclonal antibodies. All 35 MAP infected tissues were positive for MAP within macrophages, epithelioid cells and giant cells either in clumps or singly as individual bacilli. No positive staining was seen in the three uninfected normal tissues and in MAP infected tissues where primary antibodies were substituted with PBS or pre-immune serum from the same rabbit.Anti-HSP70 produced in this study offers an opportunity for improved diagnosis, screening of MAP in animal tissues and in studies on the pathogenesis of MAPItem Association of circulating serum free bioavailable and total vitamin D with cathelicidin levels among active TB patients and household contacts(Research Square, 2022) Acen, Ester Lilian; Worodria, William; Kateete, David Patrick; Olum, Ronald; Joloba, Moses L.; Akintola, Ashraf; Bbuye, Mudarshiru; Biraro Andia, IreneThe free hormone hypothesis postulates that the estimation of free circulating 25(OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D levels because it is the fraction involved in biological activities. Studies have shown that cathelicidin inhibits the growth of Mycobacterium Tuberculosis in a vitamin D-dependent manner and therefore adequate vitamin D is required for its expression. The aim of the study was to determine the association between serum-free and bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI and individuals with no TB infection. This was a cross sectional study and free and bioavailable vitamin D and LL-37 levels were measured. 95 specimens were further selected to estimate total vitamin D levels. The median free and bioavailable vitamin D levels of study participants were 3.8 ng/mL. The median LL-37 levels were 318.8 ng/mL. The mean total vitamin D levels were 18.9 ng/mL. Significantly weak inverse associations were found and vitamin D is involved in the regulation of LL-37 expression and low vitamin D levels can alter this relationship. Background Vitamin D deficiency is a prominent risk factor for TB disease worldwide (1–5). Vitamin D can be obtained in two forms, D2 is obtained through diet and D3 is obtained through skin biosynthesis (6). Its main circulating active metabolite 1, 25(OH)D is involved in regulation of antimicrobial activity and therefore important in TB therapy (7). So far, total vitamin D or 25(OH)D has been considered a better index for determining vitamin D status due to its longer half-life (6, 8–11). However, the free hormone hypothesis postulates that the estimation of free circulating 25(OH)D may be a better marker of vitamin D status and is of clinical importance compared to total vitamin D levels because it is the fraction involved in biological activities (10, 12–14). Bioavailable 25(OH)D is used to represent free vitamin D and the 10–15% fraction is loosely bound to albumin (8, 15). About 85–90% of total 25(OH)D is bound to VDBP and 10–15% is loosely bound to albumin and a small fraction remains unbound (13, 16). Free 25(OH)D is increased and readily available to cells when DBP levels are at low concentrations Previous studies report that changes in DBP levels and 25(OH)D binding affinity can lead to higher levels of free 25(OH)D, even in the absence of total vitamin D levels (17, 18). According to the Endocrine Society, total vitamin D status is classified into three groups: <20 ng/mL deficient, 21–29 ng/mL deficient, and > 30 ng/mL optimal; or sufficient amounts (19). In vitro and in vivo studies have shown that LL-37 inhibits the growth of MTB in a vitamin D-dependent manner (20, 21). Accordingly, studies have reported that adequate levels of 25(OH)D are required for expression of LL-37(22, 23). According to our systematic review, six studies reported that vitamin D regulates LL-37 expression and that vitamin D deficiency alters this function (24). Because the free fraction of vitamin D, which enters cells to cause biological effects, has not been studied with the LL-37 molecule, we hypothesize that there is no relationship between free and bioavailable vitamin D and total vitamin D with the LL-37 levels among the ATB patients, LTBI and individuals with no TB infection. This study aimed to determine the association between serum-free and bioavailable and total vitamin D with LL-37 levels in ATB patients, LTBI and individuals with no TB infection.Item Biobanking: Strengthening Uganda’s Rapid Response to COVID-19 and Other Epidemics(Biopreservation and Biobanking, 2021) Kamulegeya, Rogers; Kateete, David Patrick; Bagaya, Bernard S.; Nasinghe, Emmanuel; Muttamba, Winters; Nsubuga, Gideon; Kigozi, Edgar; Ashaba Katabazi, Fred; Nakwagala, Fred; Kalungi, Sam; Byamugisha, Josaphat; Worodria, William; Magala, Rose; Kirenga, Bruce; Joloba, Moses L.SARS-CoV-2 is a fatal disease of global public health concern. Measures to reduce its spread critically depend on timely and accurate diagnosis of virus-infected individuals. Biobanks can have a pivotal role in elucidating disease etiology, translation, and advancing public health. In this article, we show how a biobank has been a critical resource in the rapid response to coronavirus disease of 2019 (COVID-19) in Uganda. Materials and Methods: The Integrated Biorepository of H3Africa Uganda established a COVID-19 biobank. Standard Operating Procedures for sample and data collection, sample processing, and storage were developed. An e-questionnaire data tool was used to collect sociodemographic factors. Samples were collected at 7-day intervals from patients, analyzed for key parameters, processed, annotated, characterized, and stored at appropriate temperatures. Results: Stored samples have been used in validation of 17 diagnostic kits, the Cepheid Xpert Xpress SARSCoV- 2 assay, as well as a sample pooling technique for mass screening and polymerase chain reaction assay validation. Kits that passed validation were deployed for mass screening boosting early detection, isolation, and treatment of COVID-19 cases. Also, 10 applications from researchers and biotech companies have been received and approved and 4 grants have been awarded Conclusion: The CoV-Bank has proven to be an invaluable resource in the fight against the COVID-19 pandemic in Uganda, as samples have been resources in the validation and development of COVID-19 diagnostic tools, which are important in tracing and isolation of infected cases to confront, delay, and stop the spread of the SARS-CoV-2 virus.Item Evaluation of circulating serum cathelicidin levels as a potential biomarker to discriminate between active and latent tuberculosis in Uganda(PloS one, 2022) Acen, Ester Lilian; Kateete, David Patrick; Worodria, William; Olum, Ronald; Joloba, Moses L.; Bbuye, Mudarshiru; Biraro, Irene AndiaTuberculosis remains a major public health problem worldwide accounting for 1.4 million deaths annually. LL-37 is an effector molecule involved in immunity with both antimicrobial and immunomodulatory properties. The purpose of this study was to compare LL-37 circulatory levels among participants with active and latent tuberculosis and to determine its ability to discriminate between the two infectious states. Methods A cross-sectional study was performed among 56 active tuberculosis patients, 49 latent tuberculosis individuals, and 43 individuals without tuberculosis infection. The enzymelinked immunosorbent assay was used to assess LL-37 levels. Data analysis was performed using STATA software and Graph pad Prism version 8. Mann-Whitney U test was used for correlation between variables with two categories and the Kruskal-Wallis test for three or more categories. Results The study had more female participants than males, with similar median ages across the three groups, 29.5, 25.0, and 23.0 years respectively. Active tuberculosis patients had significantly higher LL-37 levels compared to those with latent tuberculosis and without tuberculosis. The median/interquartile ranges were 318.8 ng/ml (157.9–547.1), 242.2 ng/ml (136.2–579.3), 170.9 ng/ml (129.3–228.3); p = 0.002 respectively. Higher LL-37 was found in the male participant with median/interquartile range, 424.8 ng/ml (226.2–666.8) compared to the females 237.7 ng/ml (129.6–466.6); p = 0.045. LL-37 had better discriminatory potential between active tuberculosis and no tuberculosis (AUC = 0.71, sensitivity 71.4% specificity = 69.8%) than with latent tuberculosis (AUC = 0.55, sensitivity = 71.4%, specificity = 44.9%). There was moderate differentiation between latent tuberculosis and no tuberculosis (AUC = 0.63, sensitivity = 44.9% specificity = 90.7%). Conclusion Significantly higher LL-37 levels were observed among active tuberculosis patients than those without tuberculosis infection and were, therefore able to discriminate between active tuberculosis and other tuberculosis infectious states, especially with no tuberculosis. Further assessment of this biomarker as a screening tool to exclude tuberculosis is required.Item Frequency and patterns of second-line resistance conferring mutations among MDR-TB isolates resistant to a second-line drug from eSwatini, Somalia and Uganda (2014–2016)(BMC pulmonary medicine, 2019) Kateete, David Patrick; Kamulegeya, Rogers; Kigozi, Edgar; Katabazi, Fred Ashaba; Lukoye, Deus; Sebit, Sindani Ireneaus; Abdi, Hergeye; Arube, Peter; Kasule, George William; Musisi, Kenneth; Dlamini, Myalo Glen; Khumalo, Derrick; Joloba, Moses L.Pulmonary tuberculosis is a leading cause of morbidity and mortality in developing countries. Drug resistance, a huge problem in this contagious disease, is driven by point mutations in the Mycobacterium tuberculosis genome however, their frequencies vary geographically and this affects applicability of molecular diagnostics for rapid detection of resistance. Here, we report the frequency and patterns of mutations associated with resistance to second-line anti-TB drugs in multidrug-resistant (MDR) M. tuberculosis isolates from eSwatini, Somalia and Uganda that were resistant to a second-line anti-TB drug.The quinolone resistance determining region (QRDR) of gyrA/gyrB genes and the drug resistance associated fragment of rrs gene from 80 isolates were sequenced and investigated for presence of drug resistance mutations. Of the 80 isolates, 40 were MDR, of which 28 (70%) were resistant to a second-line anti-TB injectable drug, 18 (45%) were levofloxacin resistant while 12 (30%) were extensively drug resistant (XDR). The remaining 40 isolates were susceptible to anti-TB drugs. MIRU-VNTR analysis was performed for M/XDR isolates.We successfully sub-cultured 38 of the 40 M/XDR isolates. The gyrA resistance mutations (Gly88Ala/Cys/Ala, Ala90Val, Ser91Pro, Asp94Gly/Asn) and gyrB resistance mutations (Asp500His, Asn538Asp) were detected in 72.2% (13/18) and 22.2% (4/18) of the MDR and levofloxacin resistant isolates, respectively. Overall, drug resistance mutations in gyrA/gyrB QRDRs occurred in 77.8% (14/18) of the MDR and levofloxacin resistant isolates. Furthermore, drug resistance mutations a1401g and g1484 t in rrs occurred in 64.3% (18/28) of the MDR isolates resistant to a second-line anti-TB injectable drug. Drug resistance mutations were not detected in drug susceptible isolates.The frequency of resistance mutations to second-line anti-TB drugs in MDR-TB isolates resistant to second line anti-TB drugs from eSwatini, Somalia and Uganda is high, implying that rapid molecular tests are useful in detecting second-line anti-TB drug resistance in those countries. Relatedly, the frequency of fluoroquinolone resistance mutations in gyrB/QRDR is high relative to global estimates, and they occurred independently of gyrA/QRDR mutations implying that their absence in panels of molecular tests for detecting fluoroquinolone resistance may yield false negative results in our setting.Item Phylogenetic Groups And Antimicrobial Susceptibility Patterns Of Uropathogenic Escherichia Coli Clinical Isolates From Patients At Mulago National Referral Hospital, Kampala, Uganda [Version 1; Peer Review: Awaiting Peer Review(F1000Research, 2019) Katongole, Paul; Kisawuzi, Daniel Bulwadda; Bbosa, Henry Kyobe; Kateete, David Patrick; Najjuka, Christine FlorenceUropathogenic Escherichia coli (UPEC) remains the most common cause of urinary tract infections (UTIs). They account for over 80-90% of all community-acquired and 30-50% of all hospital-acquired UTIs. E. coli strains have been found to belong to evolutionary origins known as phylogenetic groups. In 2013, Clermont classified E. coli strains into eight phylogenetic groups using the quadruplex PCR method. The aim of this study was to identify the phylogenetic groups of UPEC strains in Uganda using Clermont’s quadruplex PCR method and to assess their antibiotic susceptibility patterns in Uganda. In this cross-sectional study, 140 stored uropathogenic E. coli isolates from the Clinical Microbiology Laboratory, Department of Medical Microbiology, College of Health Sciences Makerere University were subjected to phylogenetic typing by a quadruplex PCR method. Antimicrobial susceptibility testing was performed by disk diffusion method according to Clinical & Laboratory Standards Institute (CLSI) guidelines. Phenotypic detection of extended-spectrum beta-lactamase, AmpC and carbapenemases was done according to CLSI guidelines and Laboratory SOPs. Phylogenetic group B2 (40%) was the most predominant, followed by A (6.23%), clade I and II (5%), D and E (each 2.14%), B1 (1.43%) and F and C (each 0.71%). The most common resistant antibiotic was trimethoprim-sulphamethoxazole (90.71%) and the least was imipenem (1.43%). In total, 73.57% of isolates were multi-drug resistant (MDR). Antibiotic resistance was mainly detected in phylogenetic group B2 (54%).Our findings showed the high prevalence of MDR E. coli isolates, with the dominance of phylogenetic group B2. About 9% of E. coli isolates belonged to the newly described phylogroups C, E, F, and clade I and II.Item Phylogenomic analysis of Uganda influenza type-A viruses to assess their relatedness to the vaccine strains and other Africa viruses: a molecular epidemiology study(bioRxiv, 2021) Nabakooza, Grace; Owuor, David Collins; Laurent, Zaydah R. de; Owor, Nicholas; Kayiwa, John Timothy; Jjingo, Daudi; Nyaigoti Agoti, Charles; Nokes, David James; Kateete, David Patrick; Mulindwa Kitayimbwa, John; Frost, Simon David William; Lutwama, Julius JulianGenetic characterisation of circulating influenza viruses is essential for vaccine selection and mitigation of viral transmission. The current scantiness of viral genomic data and underutilisation of advanced molecular analysis methods on influenza viruses circulating in Africa has limited their extensive study and representation in the global influenza ecology. We aimed to sequence influenza type-A viruses (IAVs) that previously circulated in Uganda and characterised their genetic relatedness to the vaccine viruses and publicly available Africa IAVs. Methods: This was an observational study nested to the Uganda national influenza surveillance programme. We used Next-generation sequencing to locally generate genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) viruses collected between 2010 and 2018 from 7 districts across Uganda. A total of 206 hemagglutinin (HA), 207 neuraminidase (NA), and 213 matrix protein (MP) sequences were genetically compared to the WHO-recommended vaccines and other viruses isolated from Africa since 1994. Viral temporal and spatial divergence and circulating genetic clades were characterised using phylogenetic methods. Findings: We successfully generated gene sequences for 91·9% (215/234) viruses. Uganda A(H1N1)pdm09 and A(H3N2) virus HA, NA, and MP proteins had 96·36-99·09%, 96·49-99·39%, and 97·48-99·95% amino acid similarity, respectively, to vaccines recommended from 2010 through 2020. The local viruses incorporated amino acid substitutions (AAS) in their antigenic, receptor binding, and glycosylation sites each year causing them to antigenically drift away from vaccines. For seasons when vaccine formulations differed, Uganda IAV antigenic sites had 1-2 extra AAS relative to the Southern than Northern hemisphere vaccine viruses. All Uganda IAVs carried the adamantine-resistance marker S31N but not the neuraminidase inhibitor (NAI) resistance markers H274Y and H275Y. However, some A(H1N1)pdm09 viruses had permissive substitutions V234I, N369K, and V241I typical of NAI-resistant viruses.Item Prevalence and Antimicrobial Susceptibility Patterns of Bacteria from Milkmen and Cows with Clinical Mastitis in and around Kampala, Uganda(PloS one, 2013) Kateete, David Patrick; Kabugo, Usuf; Baluku, Hannington; Nyakarahuka, Luke; Kyobe, Samuel; Okee, Moses; Najjuka, Christine Florence; Joloba, Moses LutaakomeIdentification of pathogens associated with bovine mastitis is helpful in treatment and management decisions. However, such data from sub-Saharan Africa is scarce. Here we describe the distribution and antimicrobial susceptibility patterns of bacteria from cows with clinical mastitis in Kampala, Uganda. Due to high concern of zoonotic infections, isolates from milkmen are also described.Ninety seven milk samples from cows with clinical mastitis and 31 nasal swabs from milkmen were collected (one sample per cow/human). Fifty eight (60%) Gram-positive isolates namely Staphylococci (21), Enterococci (16), Streptococci (13), Lactococci (5), Micrococci (2) and Arcanobacteria (1) were detected in cows; only one grew Staphylococcus aureus. Furthermore, 24 (25%) coliforms namely Escherichia coli (12), Klebsiella oxytoca (5), Proteus vulgaris (2), Serratia (2), Citrobacter (1), Cedecea (1) and Leclercia (1) were identified. From humans, 24 Gram-positive bacteria grew, of which 11 were Staphylococci (35%) including four Staphylococcus aureus. Upon susceptibility testing, methicillin-resistant coagulase-negative staphylococci (CoNS) were prevalent; 57%, 12/21 in cows and 64%, 7/11 in humans. However, methicillin-resistant Staphylococcus aureus was not detected. Furthermore, methicillin and vancomycin resistant CoNS were detected in cows (Staphylococcus hominis, Staphylococcus lugdunensis) and humans (Staphylococcus scuiri). Also, vancomycin and daptomycin resistant Enterococci (Enterococcus faecalis and Enterococcus faecium, respectively) were detected in cows. Coliforms were less resistant with three pan-susceptible isolates. However, multidrug resistant Klebsiella, Proteus, Serratia, Cedecea, and Citrobacter were detected. Lastly, similar species grew from human and bovine samples but on genotyping, the isolates were found to be different. Interestingly, human and bovine Staphylococcus aureus were genetically similar (spa-CC435, spa-type t645 corresponding to ST121) but with different susceptibility patterns.CoNS, Enterococci, Streptococci, and Escherichia coli are the predominant pathogens associated with clinical bovine-mastitis in Kampala, Uganda. Multidrug resistant bacteria are also prevalent. While similar species occurred in humans and cows, transmission was not detected.Item Rates Of HIV-1 Virological Suppression And Patterns Of Acquired Drug Resistance Among Fisherfolk On First-Line Antiretroviral Therapy In Uganda(Journal of Antimicrobial Chemotherapy, 2019) Omooja, Jonah; Nannyonjo, Maria; Sanyu, Grace; Nabirye, Stella E.; Nassolo, Faridah; Lunkuse, Sandra; Kapaata, Anne; Segujja, Farouk; Kateete, David Patrick; Ssebaggala, Eric; Bbosa, Nicholas; Aling, Emmanuel; Nsubuga, Rebecca N.; Kaleebu, Pontiano; Ssemwanga, DeogratiusWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART.We enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression.The overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03–0.54)] and VL ≥10000 copies/mL (aOR: 3.48; 95% CI: 1.37–8.85) were ADR correlates. The pooling strategies for VL testing with a negative predictive value (NPV) of ≥95.2% saved US $20320 (43.5%) in VL testing costs.We observed high virological suppression rates among these highly mobile fisherfolk; however, there was widespread ADR among those with VF at the first VL testing prior to intensive adherence counselling. Timely treatment switching and adherence support is recommended for better treatment outcomes. Adoption of pooled VL testing could be cost effective, particularly in resource-limited settings.Item Rhomboids of Mycobacteria: Characterization Using an aarA Mutant of Providencia stuartii and Gene Deletion in Mycobacterium smegmatis(Plos One, 2012) Kateete, David Patrick; Katabazi, Fred Ashaba; Okeng, Alfred; Okee, Moses; Musinguzi, Conrad; Asiimwe, Benon Byamugisha; Kyobe, Samuel; Asiimwe, Jeniffer; Boom, W. Henry; Joloba, Moses LutaakomeRhomboids are ubiquitous proteins with unknown roles in mycobacteria. However, bioinformatics suggested putative roles in DNA replication pathways and metabolite transport. Here, mycobacterial rhomboid-encoding genes were characterized; first, using the Providencia stuartii null-rhomboid mutant and then deleted from Mycobacterium smegmatis for additional insight in mycobacteria.Using in silico analysis we identified in M. tuberculosis genome the genes encoding two putative rhomboid proteins; Rv0110 (referred to as “rhomboid protease 1”) and Rv1337 (“rhomboid protease 2”). Genes encoding orthologs of these proteins are widely represented in all mycobacterial species. When transformed into P. stuartii null-rhomboid mutant (ΔaarA), genes encoding mycobacterial orthologs of “rhomboid protease 2” fully restored AarA activity (AarA is the rhomboid protein of P. stuartii). However, most genes encoding mycobacterial “rhomboid protease 1” orthologs did not. Furthermore, upon gene deletion in M. smegmatis, the ΔMSMEG_4904 single mutant (which lost the gene encoding MSMEG_4904, orthologous to Rv1337, “rhomboid protease 2”) formed the least biofilms and was also more susceptible to ciprofloxacin and novobiocin, antimicrobials that inhibit DNA gyrase. However, the ΔMSMEG_5036 single mutant (which lost the gene encoding MSMEG_5036, orthologous to Rv0110, “rhomboid protease 1”) was not as susceptible. Surprisingly, the double rhomboid mutant ΔMSMEG_4904–ΔMSMEG_5036 (which lost genes encoding both homologs) was also not as susceptible suggesting compensatory effects following deletion of both rhomboid-encoding genes. Indeed, transforming the double mutant with a plasmid encoding MSMEG_5036 produced phenotypes of the ΔMSMEG_4904 single mutant (i.e. susceptibility to ciprofloxacin and novobiocin).Mycobacterial rhomboid-encoding genes exhibit differences in complementing aarA whereby it's only genes encoding “rhomboid protease 2” orthologs that fully restore AarA activity. Additionally, gene deletion data suggests inhibition of DNA gyrase by MSMEG_4904; however, the ameliorated effect in the double mutant suggests occurrence of compensatory mechanisms following deletion of genes encoding both rhomboids.Item Species And Drug Susceptibility Profiles Of Staphylococci Isolated From Healthy Children In Eastern Uganda(PloS one, 2020) Kateete, David Patrick; Asiimwe, Benon B.; Mayanja, Raymond; Najjuka, Christine Florence; Rutebemberwa, ElizeusStaphylococci are a key component of the human microbiota, and they mainly colonize the skin and anterior nares. However, they can cause infection in hospitalized patients and healthy individuals in the community. Although majority of the Staphylococcus aureus strains are coagulase-positive, some do not produce coagulase, and the isolation of coagulase-positive non-S. aureus isolates in humans is increasingly being reported. Therefore, sound knowledge of the species and characteristics of staphylococci in a given setting is important, especially isolates from children and immunocompromised individuals. The spectrum of Staphylococcus species colonizing children in Uganda is poorly understood; here, we aimed to determine the species and characteristics of staphylococci isolated from children in Eastern Uganda. Seven hundred and sixty four healthy children less than 5 years residing in Iganga and Mayuge districts in Eastern Uganda were enrolled. A total of 513 staphylococci belonging to 13 species were isolated from 485 children (63.5%, 485/764), with S. aureus being the dominant species (37.6%, 193/513) followed by S. epidermidis (25.5%, 131/513), S. haemolyticus (2.3%, 12/513), S. hominis (0.8%, 4/513) and S. haemolyticus/lugdunensis (0.58%, 3/513). Twenty four (4.95%, 24/485) children were co-colonized by two or more Staphylococcus species. With the exception of penicillin, antimicrobial resistance (AMR) rates were low; all isolates were susceptible to vancomycin, teicoplanin, linezolid and daptomycin. The prevalence of methicillin resistance was 23.8% (122/513) and it was highest in S. haemolyticus (66.7%, 8/12) followed by S. aureus (28.5%, 55/193) and S. epidermidis (23.7%, 31/131). The prevalence of multidrug resistance was 20.3% (104/513), and 59% (72/122) of methicillin resistant staphylococci were multidrug resistant. Four methicillin susceptible S. aureus isolates and a methicillin resistant S. scuiri isolate were mupirocin resistant (high-level). The most frequent AMR genes were mecA, vanA, ant(4')-Ia, and aac(6')-Ie- aph(2'')-Ia, pointing to presence of AMR drivers in the community.Item Unique Circulating microRNA Profiles in Epidemic Kaposi’s Sarcoma(Research Square, 2020) Muwonge, Haruna; Kasujja, Hassan; Atugonza, Carolyne; Kasolo, Josephine; Lugaajju, Allan; Nfambi, Joshua; Damani, Ali Moses; Sembajwe, Larry Fred; Kimuli, Ivan; Nakazzi, Faith; Nakanjako, Damalie; Kateete, David Patrick; Bwanga, FreddieThe Human herpesvirus 8 (HHV-8), causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS, and is the most common HIV-related malignancy worldwide. Lack of a diagnostic assay to detect latent and early stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled the unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based non-invasive biomarker assay for Epidemic KS. This was a comparative cross-sectional study involving 27 patients with epidemic KS, and 27 HIVpositive adults with no prior diagnosis, or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants respectively. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA was performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyze the sequencing data.Item Validity of Air Quality as a Measure of Human Mobility in Uganda. The COVID-19 Context(Research Square, 2022) Galiwango, Ronald; Bainomugisha, Engineer; Kivunike, Florence; Kateete, David Patrick; Jjingo, DaudiMobility patterns are valuable in identifying transmission patterns for infectious diseases and in deriving contact matrices that are used to parametrize mathematical models. Aggregated location data from mobile phones have been the main means of measuring human mobility on a population level. However, these data come with several limitations related to individual privacy, access and restriction of the GPS location by the user that limit their use. Methods We explored the viability of using ground monitored air quality data as an alternative to aggregated location data from mobile phones, as a measure of human mobility in two cities in Uganda. We determined associations between air quality and human mobility; and the effect of mobility restrictions on mobility and air quality using Pearson correlation (R), multivariate regression and visualized these relationships using scatter plots. Results Daily mean levels for PM2.5 in both cities were consistently higher than the WHO guideline limit, with a mean of 77.0μg/m3 (Range = 22.0–309) for Kampala and 60.0μg/m3 (Range = 18.2–331) for Wakiso. PM10 levels had a mean of 84.6μg/m3 (Range = 25.0–318) in Kampala and 67.9μg/m3 (Range = 21.0– 340) in Wakiso. PM2.5 was negatively correlated with the government response stringency index for Kampala (R = -0.31, p < 0.001) and Wakiso (R = -0.21, p < 0.001). In Kampala, PM2.5 was positively associated with movement in grocery and pharmacy (R = 0.24, p < 0.001), parks (R = 0.25, p < 0.001), retail and recreation (R = 0.24, p < 0.001), transit stations (R = 0.3, p < 0.001) and work places (R = 0.2, p < 0.001); and negatively correlated with movement in residential places (R = -0.3, p < 0.001). Only associations between PM2.5 and movement in workplaces and residential places were statistically significant in Wakiso (R = 0.14, p < 0.001 and R = -0.19, p = 0.003 respectively). Conclusions These findings suggest that air quality data are linked to human mobility data and could thus be used to monitor human movement patterns. This work represents a pioneer study to empirically and quantitatively assess the value of air quality data as a surrogate for human mobility in Uganda.