Browsing by Author "Kumbakumba, Elias"
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Item The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda(Science translational medicine, 2020) Paulson, Joseph N.; Williams, Brent L.; Hehnly, Christine; Mishra, Nischay; Sinnar, Shamim A.; Zhang, Lijun; Ssentongo, Paddy; Kabachelor, Edith Mbabazi; Wijetunge, Dona S. S.; Bredow, Benjamin von; Mulondo, Ronnie; Kiwanuka, Julius; Bajunirwe, Francis; Bazira, Joel; Bebell, Lisa M.; Burgoine, Kathy; Couto-Rodriguez, Mara; Ericson, Jessica E.; Erickson, Tim; Ferrari, Matthew; Gladstone, Melissa; Guo, Cheng; Haran, Murali; Hornig, Mady; Isaacs, Albert M.; Kaaya, Brian Nsubuga; Kangere, Sheila M.; Kulkarni, Abhaya V.; Kumbakumba, Elias; Li, Xiaoxiao; Limbrick, David D.; Magombe, Joshua; Morton, Sarah U.; Mugamba, John; Ng, James; Olupot, Peter Olupot; Onen, Justin; Peterson, Mallory R.; Roy, Farrah; Sheldon, Kathryn; Townsend, Reid; Weeks, Andrew D.; Whalen, Andrew J.; Quackenbush, John; Ssenyonga, Peter; Galperin, Michael Y.; Almeida, Mathieu; Atkins, Hannah; Warf, Benjamin C.; Lipkin, W. Ian; Broach, James R.; Schiff, Steven J.Postinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH from Paenibacillus, upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain of P. thiaminolyticus. In mice, this isolate designated strain Mbale, was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections.Item Changes in Food Insecurity, Nutritional Status, and Physical Health Status After Antiretroviral Therapy Initiation in Rural Uganda(Journal of acquired immune deficiency syndromes, 2012) Weiser, Sheri D.; Gupta, Reshma; Tsai, Alexander C.; Frongillo, Edward A.; Grede, Nils; Kumbakumba, Elias; Kawuma, Annet; Hunt, Peter W.; Bangsberg, David R.; Martin, Jeffrey N.To investigate whether time on antiretroviral therapy (ART) is associated with improvements in food security and nutritional status, and the extent to which associations are mediated by improved physical health status. The Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of HIV-infected adults newly initiating ART in Mbarara, Uganda. Participants initiating ART underwent quarterly structured interview and blood draws. The primary explanatory variable was time on ART, constructed as a set of binary variables for each 3-month period. Outcomes were food insecurity, nutritional status, and PHS. We fit multiple regression models with cluster-correlated robust estimates of variance to account for within-person dependence of observations over time, and analyses were adjusted for clinical and sociodemographic characteristics.Item A Cohort Study of Morbidity, Mortality and Health Seeking Behavior following Rural Health Center Visits by Children under 12 in Southwestern Uganda(PLoS One, 2015) Wiens, Matthew O.; Gan, Heng; Barigye, Celestine; Kumbakumba, Elias; Kabakyenga, Jerome; Larson, Charles P.; MacLeod, Stuart M.Children discharged from hospitals in developing countries are at high risk of morbidity and mortality. However, few data describe these outcomes among children seen and discharged from rural outpatient centers. The objective of this exploratory study was to identify predictors of immediate and follow-up morbidity and mortality among children visiting a rural health center in Uganda. Subjects 0–12 years of age seeking care with a caregiver were consecutively enrolled from a single rural health center in Southwestern Uganda. Baseline variables were collected by research nurses and outcomes of referral, admission or death were recorded (immediate events). Death, hospital admission and health seeking occurring during the 30 days following the clinic visit were also determined (follow-up events). Univariate logistic regression was performed to identify baseline variables associated with immediate outcome and follow-up outcomes. Over the four-month recruitment period 717 subjects were enrolled. There were 85 (11.9%) immediate events (10.1% were admitted, 2.2% were referred, none died). Forty-seven (7.8%) events occurred within 30 days after the visit (7.3% sought care from a health provider, 1.5% were admitted and 0.5% died). Variables associated with immediate events included living more than 30 minutes from the health center, age older than 5 years, having received an antimalarial prior to the visit, having seen a community health worker prior to the visit, elevated respiratory rate or temperature, and depressed weight-for-age z score or decreased oxygen saturation. These variables were not associated with follow-up events. Sick-child visits at a rural health center in South Western Uganda were associated with rates of mortality and subsequent admission of less than 2% in the period following the sick child visits. Other types of health seeking behavior occurred in approximately 7% of subjects during this same period. Several variables were associated with immediate events but there were no reliable predictors of follow-up events, possibly due to low statistical power.Item The Dynamic Relationship Between Social Support and HIV-Related Stigma in Rural Uganda(Annals of Behavioral Medicine, 2014) Takada, Sae; Weiser, Sheri D.; Kumbakumba, Elias; Muzoora, Conrad; Martin, Jeffrey N.; Hunt, Peter W.; Haberer, Jessica E.; Kawuma, Annet; Bangsberg, David R.; Tsai, Alexander C.Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support. Purpose The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma. We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma. Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations. Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigmaItem Longitudinal assessment of associations between food insecurity, antiretroviral adherence and HIV treatment outcomes in rural Uganda(AIDS (London, England), 2014) Weiser, Sheri D.; Palar, Kartika; Frongillo, Edward A.; Tsai, Alexander C.; Kumbakumba, Elias; dePee, Saskia; Hunta, Peter W.; Ragland, Kathleen; Martin, Jeffrey; Bangsber, David R.Food insecurity is a potentially important barrier to the success of antiretroviral therapy (ART) programs in resource-limited settings. We undertook a longitudinal study in rural Uganda to estimate the associations between food insecurity and HIV treatment outcomes. Longitudinal cohort study. Participants were from the Uganda AIDS Rural Treatment Outcomes study and were followed quarterly for blood draws and structured interviews. We measured food insecurity with the validated Household Food Insecurity Access Scale. Our primary outcomes were: ART nonadherence (adherence <90%) measured by visual analog scale; incomplete viral load suppression (>400 copies/ml); and low CD4þ T-cell count (<350 cells/ml). We used generalized estimating equations to estimate the associations, adjusting for socio-demographic and clinical variables.Item Newborn care knowledge and practices among care givers of newborns and young infants attending a regional referral hospital in Southwestern Uganda(Public Library of Science, 2024-05-07) Nampijja, Dorah; Kyoyagala, Stella; Najjingo, Elizabeth; Najjuma, Josephine N; Byamukama, Onesmus; Kyasimire, Lydia; Kabakyenga, Jerome; Kumbakumba, EliasA child born in developing countries has a 10 times higher mortality risk compared to one born in developed countries. Uganda still struggles with a high neonatal mortality rate at 27/1000 live births. Majority of these death occur in the community when children are under the sole care of their parents and guardian. Lack of knowledge in new born care, inappropriate new born care practices are some of the contributors to neonatal mortality in Uganda. Little is known about parent/caregivers’ knowledge, practices and what influences these practices while caring for the newborns. We systematically studied and documented newborn care knowledge, practices and associated factors among parents and care givers. To assess new born care knowledge, practices and associated factors among parents and care givers attending MRRH. We carried out a quantitative cross section methods study among caregivers of children from birth to six weeks of life attending a regional referral hospital in south western Uganda. Using pretested structured questionnaires, data was collected about care givers’ new born care knowledge, practices and the associated factors. Data analysis was done using Stata version 17.0. We interviewed 370 caregivers, majority of whom were the biological mothers at 86%. Mean age was 26 years, 14% were unemployed and 74% had monthly earning below the poverty line. Mothers had a high antenatal care attendance of 97.6% and 96.2% of the deliveries were at a health facility Care givers had variant knowledge of essential newborn care with associated incorrect practices. Majority (84.6%) of the respondents reported obliviousness to putting anything in the babies’ eyes at birth, however, breastmilk, water and saliva were reportedly put in the babies’ eyes at birth by some caregivers. Hand washing was not practiced at all in 16.2% of the caregivers before handling the newborn. About 7.4% of the new borns received a bath within 24 hours of delivery and 19% reported use of herbs. Caregivers practiced adequate thermal care 87%. Cord care practices were inappropriate in 36.5%. Only 21% of the respondents reported initiation of breast feeding within 1 hour of birth, Prelacteal feeds were given by 37.6% of the care givers, water being the commonest prelacteal feed followed by cow’s milk at 40.4 and 18.4% respectively. Majority of the respondents had below average knowledge about danger signs in the newborn where 63% and mean score for knowledge about danger signs was 44%. Caretaker’s age and relationship with the newborn were found to have a statistically significant associated to knowledge of danger signs in the newborn baby. There are variable incorrect practices in the essential new born care and low knowledge and awareness of danger signs among caregivers of newborn babies. There is high health center deliveries and antenatal care attendance among the respondents could be used as an opportunity to increase caregiver awareness about the inappropriate practices in essential newborn care and the danger signs in a newborn.Item The PAediatric Risk Assessment (PARA) Mobile App to Reduce Postdischarge Child Mortality: Design, Usability, and Feasibility for Health Care Workers in Uganda(JMIR mHealth and uHealth, 2016) English, Lauren Lacey; Kumbakumba, Elias; Larson, Charles P.; Barigye, Celestine; Ndamira, Andrew; Kabakyenga, Jerome; Wiens, Matthew O.Postdischarge death in children is increasingly being recognized as a major contributor to overall child mortality. The PAediatric Risk Assessment (PARA) app is an mHealth tool developed to aid health care workers in resource-limited settings such as Sub-Saharan Africa to identify pediatric patients at high risk of both in-hospital and postdischarge mortality. The intended users of the PARA app are health care workers (ie, nurses, doctors, and clinical officers) with varying levels of education and technological exposure, making testing of this clinical tool critical to successful implementation.Item 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, TobiasA 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.Item Post-discharge mortality among children under 5 years admitted with suspected sepsis in Uganda: a prospective multi-site study(medRxiv, 2023) Wiens, Matthew O.; Kumbakumba, Elias; Sherine, Sheila Oyella; Byaruhanga, Emmanuel; Barigye, CelestineSubstantial mortality occurs after hospital discharge in children under 5 years old with suspected sepsis. A better understanding of its epidemiology is needed for effective interventions aimed at reducing child mortality in resource limited settings.Item 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, JeromeIn 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.Item Prospective Study of the Mental Health Consequences of Sexual Violence Among Women Living With HIV in Rural Uganda(Journal of interpersonal violence, 2016) Tsai, Alexander C.; Wolfe, William R.; Kumbakumba, Elias; Kawuma, Annet; Hunt, Peter W.; Martin, Jeffrey N.; Bangsberg, David R.; Weiser, Sheri D.The association between sexual violence and depression is well known, but the temporal aspects of the association have not been well established. We analyzed data from a cohort of 173 HIV-positive women in rural Uganda who were interviewed every 3 months for a median of 1.8 years of follow-up. The method of generalized estimating equations (GEE) was used to model the marginal expectation of depression symptom severity (Hopkins Symptom Checklist for Depression), mental health–related quality of life (MOS-HIV Mental Health Summary), and heavy drinking (Alcohol Use Disorders Identification Test) as a function of self-reported forced-sex victimization in the 3 months prior to interview.Item Scheduled Follow-Up Referrals and Simple Prevention Kits Including Counseling to Improve Post-Discharge Outcomes Among Children in Uganda: A Proof-of-Concept Study(Global Health: Science and Practice, 2016) Wiens, Matthew O.; Kumbakumba, Elias; Larson, Charles P.; Moschovis, Peter P.; Barigye, Celestine; Kabakyenga, Jerome; Ndamira, Andrew; Kissoon, Niranjan; Ansermino, J. MarkRecurrent illness following hospital discharge is a major contributor to childhood mortality in resource-poor countries. Yet post-discharge care is largely ignored by health care workers and policy makers due to a lack of resources to identify children with recurrent illness and a lack of cohesive systems to provide care. The purpose of this proof-of-concept study was to evaluate the effectiveness of a bundle of interventions at discharge to improve health outcomes during the vulnerable post-discharge period. The study was conducted between December 2014 and April 2015. Eligible children were between ages 6 months and 5 years who were admitted with a suspected or proven infectious disease to one of two hospitals in Mbarara, Uganda. A bundle of interventions was provided at the time of discharge. This bundle included post-discharge referrals for follow-up visits and a discharge kit. The post-discharge referral was to ensure follow-up with a nearby health care provider on days 2, 7, and 14 following discharge. The discharge kit included brief educational counseling along with simple preventive items as incentives (soap, a mosquito net, and oral rehydration salts) to reinforce the education. The primary study outcome was the number of post-discharge referral visits completed. Secondary study outcomes included satisfaction with the intervention, rates of readmission after 60 days, and post-discharge mortality rates. In addition, outcomes were compared with a historical control group, enrolled using the same inclusion criteria and outcome-ascertainment methods. During the study, 216 children were admitted, of whom 14 died during hospitalization. Of the 202 children discharged, 85% completed at least 1 of the 3 follow-up referral visits, with 48% completing all 3 visits. Within 60 days after discharge, 22 children were readmitted at least once and 5 children (2.5%) died. Twelve (43%) readmissions occurred during a scheduled follow-up visit. Compared with prospectively enrolled historical controls, the post-discharge referral for follow-up increased the odds of readmission (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.14 to 3.23) and care sought after discharge (OR, 14.61; 95% CI, 9.41 to 22.67). Overall satisfaction with the bundle of interventions was high, with most caregivers strongly agreeing that the discharge kit and post-discharge referrals improved their ability to care for their child. Interventions initiated at the time of discharge have the potential to profoundly affect the landscape of care during illness recovery and lead to significantly improved outcomes among children under 5 years of age.Item Technical Results from a trial of the FREO2 Low-Pressure Oxygen Storage system, Mbarara Regional Referral Hospital, Uganda(Plos one, 2021) Peake, David; Kumbakumba, Elias; Bagayana, Sheillah; Barigye, Celestine; Muhumuza, Ivan; Kiwanuka, Frank; Semata, Patrick; Rassool, KevinIncreased access to reliable medical oxygen would reduce the global burden of pneumonia. Oxygen concentrators have been shown to be an effective solution, however they have significant drawbacks when used in low-resource environments where pneumonia burden is the heaviest. Low quality grid power can damage oxygen concentrators and blackouts can prevent at-risk patients from receiving continual oxygen therapy. Gaps in prescribed oxygen flow can result in acquired brain injuries, extended hypoxemia and death. The FREO2 Low-Pressure Oxygen Storage (LPOS) system consists of a suite of improvements to a standard oxygen concentrator which address these limitations. This study reports the technical results of a field trial of the system in Mbarara, Uganda. During this trial, oxygen supplied from the LPOS system was distributed to four beds in the paediatric ward of Mbarara Regional Referral Hospital. Over a three-month period, medical-grade oxygen was made available to patients 100% of the time. This period was sufficient to quantify the ability of the LPOS system to deal with blackouts, maintenance, and an unscheduled repair to the LPOS store.