Browsing by Author "Businge, Stephen"

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    Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the “PI-POC” Trial
    (JMIR research protocols, 2020) Gaudenzi, Giulia; Kumbakumba, Elias; Rasti, Reza; Nanjebe, Deborah; Réu, Pedro; Nyehangane, Dan; Mårtensson, Andreas; Nassejje, Milly; Karlsson, Jens; Mzee, John; Nilsson, Peter; Businge, Stephen; Loh, Edmund; Boum, Yap; Andersson-Svahn, Helene; Gantelius, Jesper; Mwanga-Amumpaire, Juliet; Alfvén, Tobias
    A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
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    Prediction models for post-discharge mortality among under-five children with suspected sepsis in Uganda: A multicohort analysis
    (Public Library of Science, 2024-05) Wiens, Matthew O; Nguyen, Vuong; Bone, Jeffrey N.; Kumbakumba, Elias; Businge, Stephen; Tagoola, Abner; Sherine, Sheila Oyella; Byaruhanga, Emmanuel; Ssemwanga, Edward; Barigye, Celestine; Nsungwa, Jesca; Olaro, Charles; Ansermino, J. Mark; Kissoon, Niranjan; Singer, Joel; Larson, Charles P.; Lavoie, Pascal M; Dunsmuir, Dustin; Moschovis, Peter P.; Novakowski, Stefanie; Komugisha, Clare; Tayebwa, Mellon; Mwesigwa, Douglas; Knappett, Martina; West, Nicholas; Mugisha, Nathan Kenya; Kabakyenga, Jerome
    In many low-income countries, over five percent of hospitalized children die following hospital discharge. The lack of available tools to identify those at risk of post-discharge mortality has limited the ability to make progress towards improving outcomes. We aimed to develop algorithms designed to predict post-discharge mortality among children admitted with suspected sepsis. Four prospective cohort studies of children in two age groups (0–6 and 6–60 months) were conducted between 2012–2021 in six Ugandan hospitals. Prediction models were derived for six-months post-discharge mortality, based on candidate predictors collected at admission, each with a maximum of eight variables, and internally validated using 10-fold cross-validation. 8,810 children were enrolled: 470 (5.3%) died in hospital; 257 (7.7%) and 233 (4.8%) post-discharge deaths occurred in the 0-6-month and 6-60-month age groups, respectively. The primary models had an area under the receiver operating characteristic curve (AUROC) of 0.77 (95%CI 0.74–0.80) for 0-6-month-olds and 0.75 (95%CI 0.72–0.79) for 6-60-month-olds; mean AUROCs among the 10 cross-validation folds were 0.75 and 0.73, respectively. Calibration across risk strata was good: Brier scores were 0.07 and 0.04, respectively. The most important variables included anthropometry and oxygen saturation. Additional variables included: illness duration, jaundice-age interaction, and a bulging fontanelle among 0-6-month-olds; and prior admissions, coma score, temperature, age-respiratory rate interaction, and HIV status among 6-60-month-olds. Simple prediction models at admission with suspected sepsis can identify children at risk of post-discharge mortality. Further external validation is recommended for different contexts. Models can be digitally integrated into existing processes to improve peri-discharge care as children transition from the hospital to the community.