Browsing by Author "Kiggundu, Reuben"
Now showing 1 - 9 of 9
Results Per Page
Sort Options
Item Adjunctive sertraline for HIV-associated cryptococcal meningitis: a randomised, placebo-controlled, double-blind phase 3 trial(The Lancet infectious diseases, 2019-08-30) Rhein, Joshua; Tugume, Lillian; Nuwagira, Edwin; Mpoza, Edward; Kiggundu, Reuben; Ssebambulidde, Kenneth; Boulware, David R.Identifying new antifungals for cryptococcal meningitis is a priority given the inadequacy of current therapy. Sertraline has previously shown in vitro and in vivo activity against cryptococcus. We aimed to assess the efficacy and cost-effectiveness of adjunctive sertraline in adults with HIV-associated cryptococcal meningitis compared with placebo.Item Adjunctive Sertraline in HIV-associated Cryptococcal Meningitis: A Randomized, Placebo-controlled, Double-blind Phase 3 Trial(The Lancet infectious diseases, 2019) Rhein, Joshua; Hullsiek, Kathy Huppler; Tugume, Lillian; Nuwagira, Edwin; Mpoza, Edward; Evans, Emily E.; Kiggundu, Reuben; Ssebambulidde, Kenneth; Akampurira, Andrew; Bangdiwala, Ananta S.; Abassi, Mahsa; Musubire, Abdu K.; Muzoora, Conrad; Meya, David B.; Boulware, David R.Identifying new antifungals for cryptococcal meningitis is a priority given the inadequacy of current therapy. Sertraline has previously shown in vitro and in vivo activity against cryptococcus. We aimed to assess the efficacy and cost-effectiveness of adjunctive sertraline in adults with HIV-associated cryptococcal meningitis compared with placebo.In this double-blind, randomised, placebo-controlled trial, we recruited HIV-positive adults with cryptococcal meningitis from two hospitals in Uganda. Participants were randomly assigned (1:1) to receive standard therapy with 7–14 days of intravenous amphotericin B (0·7–1·0 mg/kg per day) and oral fluconazole (starting at 800 mg/day) with either adjunctive sertraline or placebo. Sertraline was administered orally or via nasogastric tube at a dose of 400 mg/day for 2 weeks, followed by 200 mg/day for 12 weeks, then tapered off over 3 weeks. The primary endpoint was 18-week survival, analysed by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01802385.Between March 9, 2015, and May 29, 2017, we screened 842 patients with suspected meningitis and enrolled 460 of a planned 550 participants, at which point the trial was stopped for futility. Three patients in the sertraline group and three patients in the placebo group were lost to follow-up and therefore discontinued before study end. At 18 weeks, 120 (52%) of 229 patients in the sertraline group and 106 (46%) of 231 patients in the placebo group had died (hazard ratio 1·21, 95% CI 0·93–1·57; p=0·15). The fungal clearance rate from cerebrospinal fluid was similar between groups (0·43 –log10 CFU/mL per day [95% CI 0·37–0·50] in the sertraline group vs 0·47 –log10 CFU/mL per day [0·40–0·54] in the placebo group; p=0·59), as was occurrence of grade 4 or 5 adverse events (72 [31%] of 229 vs 75 [32%] of 231; p=0·98), most of which were associated with amphotericin B toxicity. Sertraline did not reduce mortality and should not be used to treat patients with HIV-associated cryptococcal meningitis. The reasons for sertraline inactivity appear to be multifactorial and might be associated with insufficient duration of therapeutic sertraline concentrations.Item Development and evaluation of a continuous quality improvement programme for antimicrobial stewardship in six hospitals in Uganda(BMJ Open Quality, 2023) Kiggundu, Reuben; Waswa, J. P.; Nakambale, Hilma N.; Kakooza, Francis; Kassuja, Hassan; Murungi, Marion; Akello, Harriet; Morries, Seru; Joshi, Mohan P.; Stergachis, Andy; Konduri, NiranjanAppropriate antimicrobial use is essential for antimicrobial stewardship (AMS). Ugandan hospitals are making efforts to improve antibiotic use, but improvements have not been sufficiently documented and evaluated. Methods Six Ugandan hospitals implemented AMS interventions between June 2019 and July 2022. We used the WHO AMS toolkit to set-up hospital AMS programmes and implemented interventions using continuous quality improvement (CQI) techniques and targeting conditions commonly associated with antibiotic misuse, that is, urinary tract infections (UTIs), upper respiratory tract infections (URTIs) and surgical antibiotic prophylaxis (SAP). The interventions included training, mentorship and provision of clinical guidelines to support clinical decision-making. Quarterly antibiotic use surveys were conducted. Results Data were collected for 7037 patients diagnosed with UTIs. There was an increase in the proportion of patients receiving one antibiotic for the treatment of UTI from 48% during the pre-intervention to 73.2%, p<0.01. There was a 19.2% reduction in the number of antimicrobials per patient treated for UTI p<0.01. There was an increase in use of nitrofurantoin, the first-line drug for the management of UTI. There was an increase in the use of Access antibiotics for managing UTIs from 50.4% to 53.8%. The proportion of patients receiving no antimicrobials for URTI increased from 26.3% at pre-intervention compared with 53.4% at intervention phase, p<0.01. There was a 20.7% reduction in the mean number of antimicrobials per patient for URTI from the pre-intervention to the intervention phase, from 0.8 to 0.6, respectively, p<0.001 and reduction in the number of treatment days, p=0.0163. Among patients undergoing surgery, 49.5% (2212) received SAP during the pre-intervention versus 50.5% (2169) during the intervention. Conclusions Using CQI approaches to focus on specific causes of inappropriate antibiotic use led to desirable overall reductions in antibiotic use for URTI and UTI.Item Enhancing infection prevention and control through hand hygiene compliance in six Ugandan hospitals using quality improvement approaches(Frontiers in Public Health, 2024-10-22) Kasujja, Hassan; Kiggundu, Reuben; Murungi, Marion; Bahatungire , Rony; Kajumbula , Henry; Konduri, NiranjanHand hygiene (HH) plays a crucial role in mitigating healthcare-associated infections. Improving HH compliance in healthcare facilities in resource-limited settings is urgently needed. We implemented the World Health Organization (WHO) HH improvement strategy using a continuous quality improvement (CQI) approach targeting improvement in HH compliance by healthcare workers (HCWs). An intervention was implemented in six hospitals using a longitudinal study design between May 2019 and April 2023. We set up and monitored infection prevention and control (IPC) and HH programs using WHO’s infection prevention and control assessment framework at the facility level (IPCAF) and hand hygiene self-assessment framework (HHSAF) tools. We implemented HH interventions using CQI techniques while targeting HCW HH knowledge and compliance with the WHO’s Five Moments of HH. By the end of the intervention, IPC and HH capacity improved in all six hospitals, from a median score of 547.0 and 252.5 on IPCAF and HHSAF tools at baseline to an advanced score of 635.0 and 350.0 at endline assessment, respectively. Similarly, HCWs’ HH knowledge improved in all hospitals, from a mean score of 45.0% at baseline to 76.0% at endline assessment, most notably among nurses. HH compliance, as assessed using WHO’s HH observation tool, at least doubled in all hospitals, rising from 19.9% to 53.8%, with before touching a patient registering the highest (22-fold) improvement. On linear regression analysis, no significant association was observed between HH compliance and IPCAF b = -0.0004 (95% CI -0.093, 0.93) p = 0.990, HHSAF b = 0.009 (95% CI -.0127, 0.145) p = 0.842 and HCW knowledge on HH/IPC b = -0.165 (95% CI 0.815, 0.485) p = 0.519. This is the first documented comprehensive utilization of CQI approaches to implement HH as an entry point for the development of hospital IPC programs, and evaluation of WHO tools and approaches for IPC and HH improvement in Uganda. Conclusion: Implementation of the WHO HH improvement strategy using a CQI approach can lead to remarkable improvement in HH capacity, and HCW compliance and knowledge in hospitals within resource-limited settings.Item Evaluation of Fingerstick Cryptococcal Antigen Lateral Flow Assay in HIV-Infected Persons : A Diagnostic Accuracy Study(Clinical Infectious Diseases, 2015) Williams, Darlisha A.; Kiiza, Tadeo; Kwizera, Richard; Kiggundu, Reuben; Velamakanni, Sruti; Meya, David B.; Rhein, Joshua; Boulware, David R.Cryptococcus neoformans is the most common cause of adult meningitis in sub-Saharan Africa. The cryptococcal antigen (CRAG) lateral flow assay (LFA) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (CSF). We evaluated the accuracy of the CRAG LFA using fingerstick whole blood compared with serum/plasma and CSF for diagnosing meningitis. Methods. From August 2013 to August 2014, CRAG LFA (IMMY, Norman, Oklahoma) tests were performed on fingerstick whole blood, plasma/serum, and CSF in 207 HIV-infected adults with suspected meningitis in Kampala, Uganda. Venous blood was also collected and centrifuged to obtain serum and/or plasma. CSF was tested after lumbar puncture. Results. Of 207 participants, 149 (72%) had fingerstick CRAG-positive results. There was 100% agreement between fingerstick whole blood and serum/plasma. Of the 149 fingerstick CRAG-positive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG. Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and culture, of whom 8 had CSF abnormalities (n = 3 lymphocytic pleocytosis, n = 5 elevated protein, n = 4 increased opening pressure). No persons with cryptococcal meningitis had negative fingersticks. Conclusions. The 100% agreement between whole blood, serum, and plasma CRAG LFA results demonstrates that fingerstick CRAG is a reliable bedside diagnostic test. Using point-of-care CRAG testing simplifies screening large numbers of patients and enables physicians to prioritize on whom to measure CSF opening pressure using manometers.Item Evaluation of Fingerstick Cryptococcal Antigen Lateral Flow Assay in HIV-Infected Persons: A Diagnostic Accuracy Study(Clinical Infectious Diseases, 2015) Williams, Darlisha A.; Kiiza, Tadeo; Kwizera, Richard; Kiggundu, Reuben; Velamakanni, Sruti; Meya, David B.; Rhein, Joshua; Boulware, David R.Cryptococcus neoformans is the most common cause of adult meningitis in sub-Saharan Africa. The cryptococcal antigen (CRAG) lateral flow assay (LFA) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (CSF). We evaluated the accuracy of the CRAG LFA using fingerstick whole blood compared with serum/plasma and CSF for diagnosing meningitis.From August 2013 to August 2014, CRAG LFA (IMMY, Norman, Oklahoma) tests were performed on fingerstick whole blood, plasma/serum, and CSF in 207 HIV-infected adults with suspected meningitis in Kampala, Uganda. Venous blood was also collected and centrifuged to obtain serum and/or plasma. CSF was tested after lumbar puncture.Of 207 participants, 149 (72%) had fingerstick CRAG-positive results. There was 100% agreement between fingerstick whole blood and serum/plasma. Of the 149 fingerstick CRAG-positive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG. Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and culture, of whom 8 had CSF abnormalities (n = 3 lymphocytic pleocytosis, n = 5 elevated protein, n = 4 increased opening pressure). No persons with cryptococcal meningitis had negative fingersticks.The 100% agreement between whole blood, serum, and plasma CRAG LFA results demonstrates that fingerstick CRAG is a reliable bedside diagnostic test. Using point-of-care CRAG testing simplifies screening large numbers of patients and enables physicians to prioritize on whom to measure CSF opening pressure using manometers.Item Implementation of the World Health Organization Global Antimicrobial Resistance Surveillance System in Uganda, 2015-2020: Mixed-Methods Study Using National Surveillance Data(JMIR public health and surveillance, 2021) Nabadda, Susan; Kakooza, Francis; Kiggundu, Reuben; Walwema, Richard; Bazira, Joel; Mayito, Jonathan; Mugerwa, Ibrahimm; Sekamatte, Musa; Kambugu, Andrew; Lamorde, Mohammed; Kajumbula, Henry; Mwebasa, HenryAntimicrobial resistance (AMR) is an emerging public health crisis in Uganda. The World Health Organization (WHO) Global Action Plan recommends that countries should develop and implement National Action Plans for AMR. We describe the establishment of the national AMR program in Uganda and present the early microbial sensitivity results from the program. Objective: The aim of this study is to describe a national surveillance program that was developed to perform the systematic and continuous collection, analysis, and interpretation of AMR data. Methods: A systematic qualitative description of the process and progress made in the establishment of the national AMR program is provided, detailing the progress made from 2015 to 2020. This is followed by a report of the findings of the isolates that were collected from AMR surveillance sites. Identification and antimicrobial susceptibility testing (AST) of the bacterial isolates were performed using standard methods at both the surveillance sites and the reference laboratory. Results: Remarkable progress has been achieved in the establishment of the national AMR program, which is guided by the WHO Global Laboratory AMR Surveillance System (GLASS) in Uganda. A functional national coordinating center for AMR has been established with a supporting designated reference laboratory. WHONET software for AMR data management has been installed in the surveillance sites and laboratory staff trained on data quality assurance. Uganda has progressively submitted data to the WHO GLASS reporting system. Of the 19,216 isolates from WHO GLASS priority specimens collected from October 2015 to June 2020, 22.95% (n=4411) had community-acquired infections, 9.46% (n=1818) had hospital-acquired infections, and 68.57% (n=12,987) had infections of unknown origin. The highest proportion of the specimens was blood (12,398/19,216, 64.52%), followed by urine (5278/19,216, 27.47%) and stool (1266/19,216, 6.59%), whereas the lowest proportion was urogenital swabs (274/19,216, 1.4%). The mean age was 19.1 (SD 19.8 years), whereas the median age was 13 years (IQR 28). Approximately 49.13% (9440/19,216) of the participants were female and 50.51% (9706/19,216) were male. Participants with community-acquired infections were older (mean age 28, SD 18.6 years; median age 26, IQR 20.5 years) than those with hospital-acquired infections (mean age 17.3, SD 20.9 years; median age 8, IQR 26 years). All gram-negative (Escherichia coli, Klebsiella pneumoniae, and Neisseria gonorrhoeae) and gram-positive (Staphylococcus aureus and Enterococcus sp) bacteria with AST showed resistance to each of the tested antibiotics. Conclusions: Uganda is the first African country to implement a structured national AMR surveillance program in alignment with the WHO GLASS. The reported AST data indicate very high resistance to the recommended and prescribed antibiotics for treatment of infections. More effort is required regarding quality assurance of laboratory testing methodologies to ensure optimal adherence to WHO GLASS–recommended pathogen-antimicrobial combinations. The current AMR data will inform the development of treatment algorithms and clinical guidelines.Item Restarting pre-exposure prophylaxis (PrEP) for HIV: a systematic review and meta-analysis(EClinicalMedicine, 2024) Kiggundu, Reuben; Soh, Qi R.; Tieosapjaroen, Warittha; Fairley, Christopher K.; Tucker, Joseph D.; Tang, Weiming; Zhang, Lei; Ong, Jason J.High coverage of pre-exposure prophylaxis (PrEP) will reduce HIV transmission and help end the HIV/AIDS pandemic. However, PrEP users face challenges, including long-term adherence. The study aimed to document the proportions of individuals who restart HIV PrEP after they stop and the reasons for restarting PrEP. Methods This study is a systematic review and meta-analysis. We systematically searched CINAHL, Embase, Emcare, Global Health, Medline, Scopus, and PsychINFO for peer-reviewed with no date restrictions. A grey literature search was conducted through Google search, a search of abstract books of AIDS conferences and the websites of WHO and UNAIDS. The data search was conducted in April 2023 and updated in February 2024. Two authors extracted data on the proportion of people who stopped and then restarted PrEP, reasons for restarting, and strategies to support people restarting PrEP. Two authors appraised the data using the Joanna Briggs Institute Appraisal Tools. We used a random-effects meta-analysis to pool estimates of restarting. We conducted meta-regression to determine potential sources of heterogeneity. This study is registered with PROSPERO, CRD42023416777. However, we deviated from our original plan as we did not identify enough studies for strategies to support restarting PrEP (primary objective). Subsequently, we revised our plan to strengthen our secondary objective to quantify the proportion of people who stopped and restarted PrEP, and explore possible reasons for its heterogeneity. Findings Of 988 studies, 30 unique studieswere included: 27 reported the proportion restarting PrEP, and of these, 7 also reported reasons for restarting PrEP, and 3 studies reported only on the reasons for restarting PrEP. No study evaluated interventions for restarting PrEP. For the meta-analysis, we included 27 studies. Most studies were from high-income countries (17/27, 63%) or the USA (15/27, 56%). Overall, 23.8% (95% CI: 15.9–32.7, I2 = 99.8%, N = 85,683) of people who stopped PrEP restarted PrEP. There was a lower proportion of restarting in studies from middle-income countries compared to high-income countries (adjusted odds ratio (aOR) 0.6, 95% CI: 0.50–0.73, p < 0.001). There was higher restarting in studies from Africa compared to the USA (aOR 1.55, 95% CI: 1.30–1.86), heterosexual populations compared to men who have sex with men or transgender women (aOR 1.50, 95% CI: 1.25–1.81, p < 0.001) and in studies defining restarting as those who had stopped PrEP for >1 month compared to those who stopped <1 month (aOR 1.20, 95% CI: 1.06–1.36, p < 0.001). Reasons for restarting PrEP included perceived higher risk for HIV acquisition and removal of barriers to access PrEP. In terms of quality assessment, overall, both randomised controlled trials had a low risk of bias, while the observational studies used in the meta-analysis had some potential risk of bias related to not explicitly addressing potential confounders (15/25, 60%) or not describing strategies to address incomplete follow-up (24/25, 96%). Interpretation About a quarter of people who stopped PrEP would restart, with substantial variation across countries and populations. It is important to understand the motivations and contextual factors influencing restarting PrEP and the support systems to enable restarting PrEP for those at ongoing risk.Item Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis With Negative Cerebral Spinal Fluid Analysis(Clinical infectious diseases, 2019) Ssebambulidde, Kenneth; Kwizera, Richard; Kandole, Tadeo Kiiza; Tugume, Lillian; Kiggundu, Reuben; Mpoza, Edward; Nuwagira, Edwin; Williams, Darlisha A.; Lofgren, Sarah M.; Abassi, Mahsa; Musubire, Abdu K.; Cresswell, Fiona V.; Muzoora, Conrad; Boulware, David R.; Meya, David B.; for the Adjunctive Sertraline for Treatment of HIV-associated Cryptococcal Meningitis TeamIndividuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies.We evaluated 1201 human immunodeficiency virus–seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic–symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif.We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91).Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity.