The epidemiology of antibiotic-resistant clinical pathogens in Uganda

BACKGROUND: Antibiotic resistance (ABR) is a global challenge, and its control depends on robust evidence primarily derived from surveillance systems.METHODS: We utilised a national surveillance data set to demonstrate how such evidence can be systematically generated. In doing so, we characterised the ABR profiles of priority clinical pathogens, identified associated factors, and drew inferences on antibiotic usage in Uganda.RESULTS: Of the 12 262 samples collected between 2019-21, we analysed 9033 with complete metadata. ABR was steadily increasing at a rate of 0.5% per year, with a surge in 2021 and the highest and lowest levels of penicillin and carbapenems detected in the northern (odds ratio (OR) = 2.26; P &lt; 0.001) and the northeast (OR = 0.28; P &lt; 0.001) regions of Uganda respectively. ABR was commonly observed with Escherichia coli (OR = 1.18; P &lt; 0.001) and Klebsiella pneumoniae (OR = 1.25; P &lt; 0.001) among older and male patients (61-70 years old) (OR = 1.88; P = 0.005). Multi-drug resistance (MDR) and ABR were disproportionately higher among bloodstream infections than respiratory tract infections and urinary tract infections, often caused by Acinetobacter baumannii. Co-occurrence of ABR suggests that cephalosporins such as ceftriaxone are in high use all over Uganda.CONCLUSIONS: ABR is indeed a silent pandemic, and our results suggest it is increasing at 0.5% per year, with a notable surge in 2021 likely due to coronavirus disease 2019 (COVID-19). Of concern, ABR and MDR are mainly associated with bloodstream and surgical wound infections, with a gender and age dimension. However, it is encouraging that carbapenem resistance remains relatively low. Such evidence is critical for contextualising the implementation and evaluation of national action plans.</p

Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

ABSTRACT: BACKGROUND: Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. METHODS: Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/mL) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression. RESULTS: At 12 and 24 months of ART, 72% (n=701) and 70% (n=369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/mL). Risk factors for virological failure (>1,000 copies/mL) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. CONCLUSIONS: Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy

Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda

Children living with HIV continue to be in urgent need of combined antiretroviral therapy (ART). Strategies to scale up and improve pediatric HIV care in resource-poor regions, especially in sub-Saharan Africa, require further research from these settings. We describe treatment outcomes in children treated in rural Uganda after 1 and 2 years of ART start

Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019.

BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies

Continental concerted efforts to control the seventh outbreak of Ebola Virus Disease in Uganda: the first 90 days of the response

On 20th September 2022, Uganda declared the 7th outbreak of Ebola virus disease (EVD) caused by the Sudan Ebola strain following the confirmation of a case admitted at Mubende Regional Referral Hospital. Upon confirmation, the Government of Uganda immediately activated the national incident management system to initiate response activities. Additionally, a multi-country emergency stakeholder meeting was held in Kampala; convening Ministers of Health from neighbouring Member States to undertake cross-border preparedness and response actions. The outbreak spanned 69 days and recorded a total of 164 cases (142 confirmed, 22 probable), 87 recoveries and 77 deaths (case fatality ratio of 47%). Nine out of 136 districts were affected with transmission taking place in 5 districts but spilling over in 4 districts without secondary transmission. As part of the response the Government was able to galvanise robust community mobilisation and initiated assessment of medical counter measures including therapeutics, new diagnostics and vaccines. This paper highlights the response actions put in place that contributed to the containment of this outbreak in addition to the challenges faced with a special focus on key recommendations for better control of future outbreaks

Solar-powered oxygen delivery for the treatment of children with hypoxemia: protocol for a cluster-randomized stepped-wedge controlled trial in Uganda

Background: Child mortality due to pneumonia is a major global health problem and is associated with hypoxemia. Access to safe and continuous oxygen therapy can reduce mortality; however, low-income countries may lack the necessary resources for oxygen delivery. We have previously demonstrated proof-of-concept that solar-powered oxygen (SPO 2) delivery can reliably provide medical oxygen remote settings with minimal access to electricity. This study aims to demonstrate the efficacy of SPO 2 in children hospitalized with acute hypoxemic respiratory illness across Uganda. Methods:Objectives: Demonstrate efficacy of SPO 2 in children hospitalized with acute hypoxemic respiratory illness. Study design: Multi-center, stepped-wedge cluster-randomized trial. Setting: Twenty health facilities across Uganda, a low-income, high-burden country for pediatric pneumonia. Site selection: Facilities with pediatric inpatient services lacking consistent O2 supply on pediatric wards. Participants: Children aged \u3c 5 years hospitalized with hypoxemia (saturation \u3c 92%) warranting hospital admission based on clinical judgement. Randomization methods: Random installation order generated a priori with allocation concealment. Study procedure: Patients receive standard of care within pediatric wards with or without SPO2 system installed. Outcome measures: Primary: 48-h mortality. Secondary: safety, efficacy, SPO 2 system functionality, operating costs, nursing knowledge, skills, and retention for oxygen administration. Statistical analysis of primary outcome: Linear mixed effects logistic regression model with 48-h mortality (dependent variable) as a function of SPO 2 treatment (before versus after installation), while adjusting for confounding effects of calendar time (fixed effect) and site (random effect). Sample size: 2400 patients across 20 health facilities, predicted to provide 80% power to detect a 35% reduction in mortality after introduction of SPO 2, based on a computer simulation of \u3e 5000 trials. Discussion: Overall, our study aims to demonstrate mortality benefit of SPO 2 relative to standard (unreliable) oxygen delivery. The innovative trial design (stepped-wedge, cluster-randomized) is supported by a computer simulation. Capacity building for nursing care and oxygen therapy is a non-scientific objective of the study. If successful, SPO 2 could be scaled across a variety of resource-constrained remote or rural settings in sub-Saharan Africa and beyond

Hypoxaemia prevalence and management among children and adults presenting to primary care facilities in Uganda: A prospective cohort study.

Hypoxaemia (low blood oxygen) is common among hospitalised patients, increasing the odds of death five-fold and requiring prompt detection and treatment. However, we know little about hypoxaemia prevalence in primary care and the role for pulse oximetry and oxygen therapy. This study assessed the prevalence and management of hypoxaemia at primary care facilities in Uganda. We conducted a cross sectional prevalence study and prospective cohort study of children with hypoxaemia in 30 primary care facilities in Uganda, Feb-Apr 2021. Clinical data collectors used handheld pulse oximeters to measure blood oxygen level (SpO2) of all acutely unwell children, adolescents, and adults. We followed up a cohort of children aged under 15 years with SpO2<93% by phone after 7 days to determine if the patient had attended another health facility, been admitted, or recovered. Primary outcome: proportion of children under 5 years of age with severe hypoxaemia (SpO2<90%). Secondary outcomes: severe (SpO2<90%) and moderate hypoxaemia (SpO2 90-93%) prevalence by age/sex/complaint; number of children with hypoxaemia referred, admitted and recovered. We included 1561 children U5, 935 children 5-14 years, and 3284 adolescents/adults 15+ years. Among children U5, the prevalence of severe hypoxaemia was 1.3% (95% CI 0.9 to 2.1); an additional 4.9% (3.9 to 6.1) had moderate hypoxaemia. Performing pulse oximetry according to World Health Organization guidelines exclusively on children with respiratory complaints would have missed 14% (3/21) of severe hypoxaemia and 11% (6/55) of moderate hypoxaemia. Hypoxaemia prevalence was low among children 5-14 years (0.3% severe, 1.1% moderate) and adolescents/adults 15+ years (0.1% severe, 0.5% moderate). A minority (12/27, 44%) of severely hypoxaemic patients were referred; 3 (12%) received oxygen. We followed 87 children aged under 15 years with SpO2<93%, with complete data for 61 (70%), finding low rates of referral (6/61, 10%), hospital attendance (10/61, 16%), and admission (6/61, 10%) with most (44/61, 72%) fully recovered at day 7. Barriers to referral included caregiver belief it was unnecessary (42/51, 82%), cost (8/51, 16%), and distance or lack of transport (3/51, 6%). Hypoxaemia is common among acutely unwell children under five years of age presenting to Ugandan primary care facilities. Routine pulse oximetry has potential to improve referral, management and clinical outcomes. Effectiveness, acceptability, and feasibility of pulse oximetry and oxygen therapy for primary care should be investigated in implementation trials, including economic analysis from health system and societal perspectives

Improving effective coverage of medical-oxygen services for neonates and children in health facilities in Uganda : a before-after intervention study

Background Medical oxygen services are essential for the care of acutely unwell patients. We aimed to assess the effects of a multilevel, multicomponent health-system intervention on hypoxaemia detection, oxygen therapy, and mortality among neonates and children attending level IV health centres and hospitals in Uganda. Methods For this before–after intervention study, we included children who attended paediatric or neonatal wards of 24 level IV health centres and seven general or regional referral hospitals in the Busoga and North Buganda regions of Uganda between June 1, 2020, and June 30, 2022. All neonates younger than 1 month and children aged 1 month to 14 years were eligible for inclusion. We excluded neonates who were not sick but stayed in the maternity ward for routine postnatal care. The intervention involved clinical training, mentorship, and supportive supervision; provision of pulse oximeters and cylinder-based oxygen sources; biomedical-capacity support; and support to develop and disseminate oxygen supply strategies, oxygen therapy guidelines, and lists of essential oxygen supplies. Trained research assistants extracted individual patient data from case notes using a standardised electronic data collection form. Data were collected on health-facility details, age, sex, clinical signs and symptoms, admission diagnoses, pulse oximetry readings, oxygen therapy details, and final patient outcome. The primary outcome was the proportion of admitted neonates and children with a pulse oximetry oxygen saturation reading documented in their patient case notes on day 1 of health-facility admission (ie, pulse oximetry coverage). We used mixed-effects logistic regression to evaluate the effect of the intervention. Findings We obtained data on 71 997 eligible neonates and children admitted to 31 participating health facilities; the primary analysis included 10 001 patients in the pre-intervention period (ie, June 1 to Oct 30, 2020) and 51 329 patients in the post-intervention period (ie, March 1, 2021, to June 30, 2022). Because 1356 patients had missing data for sex, 4365 (46·7%) of 9347 in the pre-intervention group and 22 831 (46·2%) of 49 410 in the post-intervention group were female; 4982 (53·3%) in the pre-intervention group and 26 579 (53·8%) in the post-intervention group were male. The proportion of neonates and children with pulse oximetry at admission increased from 2365 (23·7%) of 10 001 in the pre-intervention period to 45 029 (87·7%) of 51 328 in the post-intervention period. Adjusted analysis indicated greater likelihood of a patient receiving pulse oximetry during the post-intervention period compared with the pre-intervention period (adjusted odds ratio 40·10, 95% CI 37·38–42·93; p&lt;0·0001). Interpretation Large-scale improvements in hospital oxygen services are achievable and have the potential to improve clinical outcomes. Governments should be encouraged to develop national oxygen plans and focus investment on interventions that have been shown to be effective, including the introduction of pulse oximetry into routine hospital care and clinical and biomedical mentoring and support.De två första författarna delar förstaförfattarskapet</p

Uptake of reproductive, maternal and child health services during the first year of the COVID-19 pandemic in Uganda: A mixed methods study

Use of reproductive health (RH), maternal, newborn and child health (MNCH) services in Uganda is suboptimal. Reasons for this are complex; however, service-delivery factors such as availability, quality, staffing, and supplies, contribute substantially to low uptake. The COVID-19 pandemic threatened to exacerbate existing challenges to delivery and use of high-quality RH and MNCH services. We conducted a mixed methods study, combining secondary analysis of routine electronic health management information system (eHMIS) data with exploratory key informant interviews (KII) to examine changes in health service uptake over the course of the pandemic and to understand service delivery adaptations implemented in response. We analyzed eHMIS data for four services (family planning, facility-based deliveries, antenatal visits, and immunization for children by one year), comparing them across four time periods: pre-COVID-19, partial lockdown, total lockdown and post lockdown. Additionally, KIIs were used to document adaptations made for continuity of health services. Use of services declined substantially during total lockdown; however, rebounded quickly to earlier observed levels, during the post lockdown for all four services, especially for immunization for children by one year. KIIs identified several health services delivery adaptations. At the community level, these included: community outreaches, training some mothers as community liaisons to encourage others to seek health services, and support from local leaders to create call centers to facilitate clients transport during travel restrictions. Health facilities creatively used space to accommodate social distancing and shifted providers’ roles. District leadership reassigned health workers to facilities closest to their homes, provided vehicle passes to staff, and ambulances to transport pregnant women in critical need. WhatsApp groups facilitated communication at district level and enabled redistribution of supplies. Ministry of Health produced critical guidelines for continuity of health services. Implementing partners provided and redistributed commodities and personal protective equipment, and provided technical support, training and transport