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Globally, Healthcare-associated infections (HCAIs) pose a significant threat to patient safety and healthcare systems. In low- and middle-income countries (LMICs), the lack of adequate resources to manage HCAIs, as well as the weak healthcare system, further exacerbate the burden of these infections. Traditional surveillance methods that rely on laboratory tests are cost-intensive and impractical in these settings, leading to ineffective monitoring and delayed management of HCAIs. The rates of HCAIs in resource-limited settings have not been well established for most LMICs, despite their negative consequences. This is partly due to costs associated with surveillance systems. Syndromic surveillance, a part of active surveillance, focuses on clinical observations and symptoms rather than laboratory confirmation for HCAI detection. Its cost-effectiveness and efficiency make it a beneficial approach for monitoring HCAIs in LMICs. It provides for early warning capabilities, enabling timely identification and response to potential HCAI outbreaks. Syndromic surveillance is highly sensitive and this helps balance the challenge of low sensitivity of laboratory-based surveillance systems. If syndromic surveillance is used hand-in-hand with laboratory-based surveillance systems, it will greatly contribute to establishing the true burden of HAIs in resource-limited settings. Additionally, its flexibility allows for adaptation to different healthcare settings and integration into existing health information systems, facilitating data-driven decision-making and resource allocation. Such a system would augment the event-based surveillance system that is based on alerts and rumours for early detection of events of outbreak potential. If well streamlined and targeted, to monitor priority HCAIs such as surgical site infections, hospital-acquired pneumonia, diarrheal illnesses, the cost and burden of the effects from these infections could be reduced. This approach would offer early detection capabilities and could be expanded into nationwide HCAI surveillance networks with standardised data collection, healthcare worker training, real-time reporting mechanisms, stakeholder collaboration, and continuous monitoring and evaluation. Syndromic surveillance offers a promising strategy for combating HCAIs in LMICs. It provides early warning capabilities, conserves resources, and enhances patient safety. Effective implementation depends on strategic interventions, stakeholder collaboration, and ongoing monitoring and evaluation to ensure sustained effectiveness in HCAI detection and response. [ABSTRACT FROM AUTHOR]

Abstract Introduction: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and [...]

Introduction: The effect of long-term exposure to antiretroviral therapy (ART) on hypertension in sub-Saharan Africa remains unclear. We aimed to determine the prevalence and incidence of hypertension in people living with HIV (PLWH) with more than 10 years of ART in Uganda. Methods: The analysis was performed within a cohort of adult PLWH with more than 10 years of ART at an HIV clinic in Kampala, Uganda. Participants were eligible for this analysis if they had ≥2 follow-up visits. Hypertension was defined as two consecutive systolic blood pressure (SBP) measures greater than 140 mmHg and/or diastolic blood pressure (DBP) greater than 90 mmHg, and/or documented diagnosis and/or the initiation of antihypertensives. We determined the proportion of PLWH with hypertension at baseline and used multivariable logistic regression to determine the factors associated with prevalent hypertension. To determine the incidence of hypertension, follow-up began from the cohort baseline date and was censored at the last clinic visit or date of the event, whichever occurred earlier. Multivariable Poisson regression was used to determine the adjusted incidence rate ratios (aIRR) of hypertension according to demographic, ART, and clinical characteristics. Results: Of the 1000 ALT participants, 970 (97%) had ≥2 follow-up visits, and 237 (24.4%) had hypertension at baseline. The odds of prevalent hypertension were 1.18 for every 5-year increase in age (adjusted odds ratio (aOR) 1.18, 95% CI 1.10–1.34) and were higher among males (aOR 1.70, 95% CI 1.20–2.34), participants with diabetes mellitus (aOR 2.37, 95% CI 1.10–4.01), obesity (aOR 1.99, 95% CI 1.08–3.60), high cholesterol (aOR 1.47, 95% CI 1.16–2.01), and those with prior exposure to stavudine (aOR 2.10, 95% CI 1.35–3.52), or nevirapine (aOR 1.90, 95% CI 1.25–3.01). Of the 733 participants without hypertension at baseline, 116 (15.83%) developed hypertension during 4671.3 person-years of follow-up (incidence rate 24.8 per 1000 person-years; 95% CI 20.7–29.8). The factors associated with incident hypertension were obesity (adjusted incidence rate ratio (aIRR) 1.80, 95% CI 1.40–2.81), older age (aIRR 1.12 per 5-year increase in age, 95% CI 1.10,1.25), and renal insufficiency (aIRR1.80, 95% CI 1.40–2.81). Conclusion: The prevalence and incidence of hypertension were high in this heavily treated PLWH cohort. Therefore, with increasing ART coverage, HIV programs in SSA should strengthen the screening for hypertension in heavily treated PLWH. [ABSTRACT FROM AUTHOR]

Objective: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)‐based antiretroviral therapy (ART) versus non‐nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. Methods: Eligible people with HIV were aged ≥18 years who initiated a new three‐drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow‐up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. Results: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113–130) mmHg, 78 (70–82) mmHg, and 43 (34–50) years, respectively. Over 8380.4 person‐years (median follow‐up 1.5 [IQR 1.0–2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person‐years, 95% confidence interval [CI] 118.9–134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47–2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89–1.29). The results were similar when the analysis was stratified by ART status at baseline. Conclusion: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART‐naïve and ART‐experienced participants within RESPOND. [ABSTRACT FROM AUTHOR]

Background: Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up. Methods: Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing. Findings: Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451–716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100–200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals. Conclusions: In a Ugandan HIV clinic, ART delivery costs—including VL testing—for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions. [ABSTRACT FROM AUTHOR]

In a rural Ugandan community scaling up antiretroviral therapy (ART), we sought to determine if population-based HIV RNA levels [population viral load (VL)] decreased from 2011 to 2012.Serial cross-sectional analyses (May 2011 and May 2012) of a defined study community of 6300 persons in a district with HIV prevalence of 8%.We measured HIV-1 RNA (VL) levels on all individuals testing positive for HIV during a 5-day high-throughput multidisease community health campaign in May 2012 that recruited two-thirds of the population. We aggregated individual-level VL results into population VL metrics including the proportion of individuals with an undetectable VL and compared these VL metrics to those we previously reported for this geographic region in 2011.In 2012, 223 of 2179 adults were HIV-seropositive adults (10%). Overall, among 208 of 223 HIV-seropositive adults in whom VL was tested, 53% had an undetectable VL [95% confidence interval (CI): 46 to 60], up from 37% (95% CI: 30 to 45; P = 0.02) in 2011. Seven (3%) individuals had a VL of >100,000 copies/mL in 2012, down from 21 (13%) in 2011 (P = 0.0007). Mean log (VL) (geometric mean) was 3.18 log (95% CI: 3.06 to 3.29 log) in 2012, down from 3.62 log (95% CI: 3.46 to 3.78 log) in 2011 (P < 0.0001). Similar reductions in population VL were seen among men and women.Reductions in population VL metrics and a substantial increase in the proportion of persons with an undetectable VL were observed in a rural Ugandan community from 2011 to 2012. These findings from a resource-limited setting experiencing rapid ART scale-up may reflect a population-level effectiveness of expanding ART access. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is a major global public health concern, particularly in low- and middle-income countries where resources and infrastructure for an adequate response are limited. The World Health Organization (WHO) Global Antimicrobial Resistance Surveillance System (GLASS) was introduced in 2016 to address these challenges, outlining recommendations for priority pathogen-antibiotic combinations. Despite this initiative, implementation in Africa remains understudied. This scoping review aims to assess the current state of implementing WHO GLASS recommendations on antimicrobial sensitivity testing (AST) in Africa., Objective: The primary objective of this study is to determine the current state of implementing the WHO GLASS recommendations on AST for priority pathogen-antimicrobial combinations. The review will further document if the reporting of AST results is according to "susceptible," "intermediate," and "resistant" recommendations according to GLASS., Methods: Following the methodological framework by Arksey and O'Malley, studies published between January 2016 and November 2023 will be included. Search strategies will target electronic databases, including MEDLINE, Scopus, CINAHL, and Embase. Eligible studies will document isolates tested for antimicrobial sensitivity, focusing on WHO-priority specimens and pathogens. Data extraction will focus on key study characteristics, study context, population, and adherence to WHO GLASS recommendations on AST. Descriptive statistics involving summarizing the quantitative data extracted through measures of central tendency and variation will be used. Covidence and Microsoft Excel software will be used. This study will systematically identify, collate, and analyze relevant studies and data sources based on clear inclusion criteria to provide a clear picture of the progress achieved in the implementation of the WHO GLASS recommendations. Areas for further improvement will be documented to inform future efforts to strengthen GLASS implementation for enhanced AMR surveillance in Africa., Results: The study results are expected in August 2024., Conclusions: To our knowledge, this scoping review will be the first to comprehensively examine the implementation of WHO GLASS recommendations in Africa, shedding light on the challenges and successes of AMR surveillance in the region. Addressing these issues aims to contribute to global efforts to combat AMR., International Registered Report Identifier (irrid): PRR1-10.2196/58140., (©Mackline Hope, Reuben Kiggundu, Dathan M Byonanebye, Jonathan Mayito, Dickson Tabajjwa, Fahad Lwigale, Conrad Tumwine, Herman Mwanja, Andrew Kambugu, Francis Kakooza. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.11.2024.)

Background: It is projected that drug-resistant infections will lead to 10 million deaths annually by 2050 if left unabated. Despite this threat, surveillance data from resource-limited settings are scarce and often lack antimicrobial resistance (AMR)-related clinical outcomes and economic burden. We aim to build an AMR and antimicrobial use (AMU) data warehouse, describe the trends of resistance and antibiotic use, determine the economic burden of AMR in Uganda, and develop a machine learning algorithm to predict AMR-related clinical outcomes., Objective: The overall objective of the study is to use data-driven approaches to optimize antibiotic use and combat antimicrobial-resistant infections in Uganda. We aim to (1) build a dynamic AMR and antimicrobial use and consumption (AMUC) data warehouse to support research in AMR and AMUC to inform AMR-related interventions and public health policy, (2) evaluate the trends in AMR and antibiotic use based on annual antibiotic and point prevalence survey data collected at 9 regional referral hospitals over a 5-year period, (3) develop a machine learning model to predict the clinical outcomes of patients with bacterial infectious syndromes due to drug-resistant pathogens, and (4) estimate the annual economic burden of AMR in Uganda using the cost-of-illness approach., Methods: We will conduct a study involving data curation, machine learning-based modeling, and cost-of-illness analysis using AMR and AMU data abstracted from procurement, human resources, and clinical records of patients with bacterial infectious syndromes at 9 regional referral hospitals in Uganda collected between 2018 and 2026. We will use data curation procedures, FLAIR (Findable, Linkable, Accessible, Interactable and Repeatable) principles, and role-based access control to build a robust and dynamic AMR and AMU data warehouse. We will also apply machine learning algorithms to model AMR-related clinical outcomes, advanced statistical analysis to study AMR and AMU trends, and cost-of-illness analysis to determine the AMR-related economic burden., Results: The study received funding from the Wellcome Trust through the Centers for Antimicrobial Optimisation Network (CAMO-Net) in April 2023. As of October 28, 2024, we completed data warehouse development, which is now under testing; completed data curation of the historical Fleming Fund surveillance data (2020-2023); and collected retrospective AMR records for 599 patients that contained clinical outcomes and cost-of-illness economic burden data across 9 surveillance sites for objectives 3 and 4, respectively., Conclusions: The data warehouse will promote access to rich and interlinked AMR and AMU data sets to answer AMR program and research questions using a wide evidence base. The AMR-related clinical outcomes model and cost data will facilitate improvement in the clinical management of AMR patients and guide resource allocation to support AMR surveillance and interventions., International Registered Report Identifier (irrid): PRR1-10.2196/58116., (©Jonathan Mayito, Conrad Tumwine, Ronald Galiwango, Elly Nuwamanya, Suzan Nakasendwa, Mackline Hope, Reuben Kiggundu, Dathan M Byonanebye, Flavia Dhikusooka, Vivian Twemanye, Andrew Kambugu, Francis Kakooza. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 08.11.2024.)

Whether integrase strand transfer inhibitors (INSTIs) are associated with a higher risk of incident type 2 diabetes mellitus (DM) than other antiretroviral therapies (ART) needs to be established.MEDLINE, Embase, Web of Science, and ClinicalTrials.gov registries were searched for studies published between 1 January 2000 and 15 June 2022. Eligible studies reported incident DM or mean changes in insulin resistance measured by Homeostatic Model for Insulin Resistance (HOMA-IR) in patients on INSTIs compared with other ARTs. We performed random-effects meta-analyses to obtain pooled relative risks (RRs) with 95% CIs.A total of 16 studies were pooled: 13 studies meta-analyzed for incident diabetes with a patient population of 72 404 and 3 for changes in HOMA-IR. INSTI therapy was associated with a lower risk of incident diabetes in 13 studies (RR 0.80, 95% CI 0.67 to 0.96, I 2 =29%), of which 8 randomized controlled trials demonstrated a 22% reduced risk (RR 0.88, 95% CI 0.81 to 0.96, I 2 =0%). INSTIs had a lower risk compared with non-nucleoside reverse transcriptase inhibitors (RR 0.75, 95% CI 0.63 to 0.89, I 2 =0%) but similar to protease inhibitor-based therapy (RR 0.78, 95% CI 0.61 to 1.01, I 2 =27%). The risk was lower in studies with longer follow-up (RR 0.70, 95% CI 0.53 to 0.94, I 2 =24%) and among ART-naïve patients (RR 0.78, 95% CI 0.65 to 0.94, I 2 =3%) but increased in African populations (RR 2.99, 95% CI 2.53 to 3.54, I 2 =0%).In conclusion, exposure to INSTIs was not associated with increased risk of DM, except in the African population. Stratified analyses suggested reduced risk among ART-naïve patients and studies with longer follow-up.International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42021273040., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health., Methods: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only)., Results: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39)., Conclusions: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.)., (Copyright © 2019 Massachusetts Medical Society.)