Characterization of Antibiotic Resistance in Select Tertiary Hospitals in Uganda: An Evaluation of 2020 to 2023 Routine Surveillance Data.

Antimicrobial resistance (AMR) is a public health concern in Uganda. We sought to conduct an extended profiling of AMR burden at selected Ugandan tertiary hospitals. We analyzed routine surveillance data collected between October 2020 and March 2023 from 10 tertiary hospitals. The analysis was stratified according to the hospital unit, age, gender, specimen type, and time. Up to 2754 isolates were recovered, primarily from pus: 1443 (52.4%); urine: 1035 (37.6%); and blood: 245 (8.9%). Most pathogens were Staphylococcus aureus, 1020 (37%), Escherichia coli, 808 (29.3%), and Klebsiella spp., 200 (7.3%). Only 28% of Escherichia coli and 42% of the other Enterobacterales were susceptible to ceftriaxone, while only 44% of Staphylococcus aureus were susceptible to methicillin (56% were MRSA). Enterococcus spp. susceptibility to vancomycin was 72%. The 5-24-year-old had 8% lower ampicillin susceptibility than the >65-year-old, while the 25-44-year-old had 8% lower ciprofloxacin susceptibility than the >65-year-old. The 0-4-year-old had 8% higher ciprofloxacin susceptibility. Only erythromycin susceptibility varied by sex, being higher in males. Escherichia coli ciprofloxacin susceptibility in blood (57%) was higher than in urine (39%) or pus (28%), as was ceftriaxone susceptibility in blood (44%) versus urine (34%) or pus (14%). Klebsiella spp. susceptibility to ciprofloxacin and meropenem decreased by 55% and 47%, respectively, during the evaluation period. During the same period, Escherichia coli ciprofloxacin susceptibility decreased by 40%, while Staphylococcus aureus gentamicin susceptibility decreased by 37%. Resistance was high across the Access and Watch antibiotic categories, varying with time, age, sex, specimen type, and hospital unit. Effective antimicrobial stewardship targeted at the critical AMR drivers is urgently needed.

Anthrax bio-surveillance of livestock in Arua District, Uganda, 2017-2018.

Anthrax, caused by Bacillus anthracis, is a widespread zoonotic disease with many human cases, especially in developing countries. Even with its global distribution, anthrax is a neglected disease with scarce information about its actual impact on the community level. Due to the ecological dynamics of anthrax transmission at the wildlife-livestock interface, the Sub-Saharan Africa region becomes a high-risk zone for maintaining and acquiring the disease. In this regard, some subregions of Uganda are endemic to anthrax with regular seasonal trends. However, there is scarce data about anthrax outbreaks in Uganda. Here, we confirmed the presence of B. anthracis in several livestock samples after a suspected anthrax outbreak among livestock and humans in Arua District. Additionally, we explored the potential risk factors of anthrax through a survey within the community kraals. We provide evidence that the most affected livestock species during the Arua outbreak were cattle (86%) compared to the rest of the livestock species present in the area. Moreover, the farmers' education level and the presence of people's anthrax cases were the most critical factors determining the disease's knowledge and awareness. Consequently, the lack of understanding of the ecology of anthrax may contribute to the spread of the infection between livestock and humans, and it is critical to reducing the presence and persistence of the B. anthracis spores in the environment. Finally, we discuss the increasingly recognized necessity to strengthen global capacity using a One Health approach to prevent, detect, control, and respond to public threats in Uganda.

Implementation of the World Health Organization Global Antimicrobial Resistance Surveillance System in Uganda, 2015-2020: Mixed-Methods Study Using National Surveillance Data.

BACKGROUND: Antimicrobial 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.

Cutaneous anthrax associated with handling carcasses of animals that died suddenly of unknown cause: Arua District, Uganda, January 2015-August 2017.

BACKGROUND: Anthrax is a zoonotic disease that can be transmitted to humans from infected animals. During May-June 2017, three persons with probable cutaneous anthrax were reported in Arua District, Uganda; one died. All had recently handled carcasses of livestock that died suddenly and a skin lesion from a deceased person tested positive by PCR for Bacillus anthracis. During July, a bull in the same community died suddenly and the blood sample tested positive by PCR for Bacillus anthracis. The aim of this investigation was to establish the scope of the problem, identify exposures associated with illness, and recommend evidence-based control measures. METHODS: A probable case was defined as acute onset of a papulo-vesicular skin lesion subsequently forming an eschar in a resident of Arua District during January 2015-August 2017. A confirmed case was a probable case with a skin sample testing positive by polymerase chain reaction (PCR) for B. anthracis. Cases were identified by medical record review and active community search. In a case-control study, exposures between case-patients and frequency- and village-matched asymptomatic controls were compared. Key animal health staff were interviewed to learn about livestock deaths. RESULTS: There were 68 case-patients (67 probable, 1 confirmed), and 2 deaths identified. Cases occurred throughout the three-year period, peaking during dry seasons. All cases occurred following sudden livestock deaths in the villages. Case-patients came from two neighboring sub-counties: Rigbo (attack rate (AR) = 21.9/10,000 population) and Rhino Camp (AR = 1.9/10,000). Males (AR = 24.9/10,000) were more affected than females (AR = 0.7/10,000). Persons aged 30-39 years (AR = 40.1/10,000 population) were most affected. Among all cases and 136 controls, skinning (ORM-H = 5.0, 95%CI: 2.3-11), butchering (ORM-H = 22, 95%CI: 5.5-89), and carrying the carcass of livestock that died suddenly (ORM-H = 6.9, 95%CI: 3.0-16) were associated with illness. CONCLUSIONS: Exposure to carcasses of animals that died suddenly was a likely risk factor for cutaneous anthrax in Arua District during 2015-2017. The recommendations are investigation of anthrax burden in livestock, prevention of animal infections through vaccinations, safe disposal of the carcasses, public education on risk factors for infection and prompt treatment of illness following exposure to animals that died suddenly.

Blood Culture Testing Outcomes among Non-Malarial Febrile Children at Antimicrobial Resistance Surveillance Sites in Uganda, 2017-2018.

Blood culture (BC) processes are critical to the utility of diagnostic testing, bloodstream infection (BSI) management, and antimicrobial resistance (AMR) surveillance. While Uganda has established BC guidelines, often laboratory practice does not meet the desired standards. This compromises pathogen recovery, reliability of antimicrobial susceptibility testing, and diagnostic test utility. This study assessed laboratory BC process outcomes among non-malarial febrile children below five years of age at five AMR surveillance sites in Uganda between 2017 and 2018. Secondary BC testing data was reviewed against established standards. Overall, 959 BC specimens were processed. Of these, 91% were from female patients, neonates, infants, and young children (1-48 months). A total of 37 AMR priority pathogens were identified; Staphylococcus aureus was predominant (54%), followed by Escherichia coli (19%). The diagnostic yield was low (4.9%). Only 6.3% of isolates were identified. AST was performed on 70% (18/26) of identified AMR priority isolates, and only 40% of these tests adhered to recommended standards. Interventions are needed to improve laboratory BC practices for effective patient management through targeted antimicrobial therapy and AMR surveillance in Uganda. Further research on process documentation, diagnostic yield, and a review of patient outcomes for all hospitalized febrile patients is needed.

Outbreak of Anthrax Associated with Handling and Eating Meat from a Cow, Uganda, 2018.

On April 20, 2018, the Kween District Health Office in Kween District, Uganda reported 7 suspected cases of human anthrax. A team from the Uganda Ministry of Health and partners investigated and identified 49 cases, 3 confirmed and 46 suspected; no deaths were reported. Multiple exposures from handling the carcass of a cow that had died suddenly were significantly associated with cutaneous anthrax, whereas eating meat from that cow was associated with gastrointestinal anthrax. Eating undercooked meat was significantly associated with gastrointestinal anthrax, but boiling the meat for >60 minutes was protective. We recommended providing postexposure antimicrobial prophylaxis for all exposed persons, vaccinating healthy livestock in the area, educating farmers to safely dispose of animal carcasses, and avoiding handling or eating meat from livestock that died of unknown causes.

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.

Rabies in Uganda: rabies knowledge, attitude and practice and molecular characterization of circulating virus strains.

BACKGROUND: Rabies is a deadly preventable viral disease that affects all warm-blooded animals and widespread in many regions including Africa. The disease remains of major public health importance in Uganda. The purpose of this study was to establish Knowledge, Attitude, Practice (KAP) of Rabies in Moyo and Ntoroko districts and to characterize Rabies virus (RABV) strains from seven districts of Uganda with consistent prevalence of rabies. METHODS: KAP survey data were collected based on animal biting history by interviewing the head of the veterinary departments, the medical centers and selected households from the study sites. Data were obtained from 84 households in Ntoroko and Moyo districts. Thirty-five (35) brain samples were collected from bovine, dogs, goats, foxes, jackals ad sheep between 2011 and 2013. Samples were tested using fluorescent antibody test (FAT), One step RT-PCR (following RNA extraction) and partial RABV N gene was sequenced by Sanger method before phylogenetic and phylogeographic analyses of sequences. RESULTS: Scarcity of post-exposure prophylaxis services in the health centers was noted. Poor attitude of wound washing and deficiency of knowledge on how to handle wounds related to dog bites and the significance among household participants lacked. There is a high risk of rabies infection due to a limited dog's vaccination. Dog biting episodes in humans were of 75.00 and 62.50% in Moyo and Ntoroko districts respectively. Twenty-seven (27) samples tested positive for rabies by FAT and PCR. Ugandan sequences were closely related (97% nucleotide id) to the rabies virus sequences from Tanzania, Rwanda, Burundi, Nigeria, Central African Republic and Sudan with both the "Africa 1A" and "Africa 1B" RABV clades represented. A putative new clade 1D was also detected. CONCLUSIONS: Rabies remains a public health hazard in Uganda. There is urgent need to establish advocacy programs in both schools and communities to curtail the spread of rabies. Increasing the knowledge regarding wound washing, post-exposure prophylaxis and dogs vaccination would enhance prevention of rabies. A strong collaboration between medical and veterinary sectors under a one health platform is required to ensure sufficient preventative services to the communities.

Risk assessment of Ebola virus disease spreading in Uganda using a two-layer temporal network.

Network-based modelling of infectious diseases apply compartmental models on a contact network, which makes the epidemic process crucially dependent on the network structure. For highly contagious diseases such as Ebola virus disease (EVD), interpersonal contact plays the most vital role in human-to-human transmission. Therefore, for accurate representation of EVD spreading, the contact network needs to resemble the reality. Prior research has mainly focused on static networks (only permanent contacts) or activity-driven networks (only temporal contacts) for Ebola spreading. A comprehensive network for EVD spreading should include both these network structures, as there are always some permanent contacts together with temporal contacts. Therefore, we propose a two-layer temporal network for Uganda, which is at risk of an Ebola outbreak from the neighboring Democratic Republic of Congo (DRC) epidemic. The network has a permanent layer representing permanent contacts among individuals within the family level, and a data-driven temporal network for human movements motivated by cattle trade, fish trade, or general communications. We propose a Gillespie algorithm with the susceptible-infected-recovered (SIR) compartmental model to simulate the evolution of EVD spreading as well as to evaluate the risk throughout our network. As an example, we applied our method to a network consisting of 23 districts along different movement routes in Uganda starting from bordering districts of the DRC to Kampala. Simulation results show that some regions are at higher risk of infection, suggesting some focal points for Ebola preparedness and providing direction to inform interventions in the field. Simulation results also show that decreasing physical contact as well as increasing preventive measures result in a reduction of chances to develop an outbreak. Overall, the main contribution of this paper lies in the novel method for risk assessment, which can be more precise with an increasing volume of accurate data for creating the network model.

Individual-based network model for Rift Valley fever in Kabale District, Uganda.

Rift Valley fever (RVF) is a zoonotic disease, that causes significant morbidity and mortality among ungulate livestock and humans in endemic regions. In East Africa, the causative agent of the disease is Rift Valley fever virus (RVFV) which is primarily transmitted by multiple mosquito species in Aedes and Mansonia genera during both epizootic and enzootic periods in a complex transmission cycle largely driven by environmental and climatic factors. However, recent RVFV activity in Uganda demonstrated the capability of the virus to spread into new regions through livestock movements, and underscored the need to develop effective mitigation strategies to reduce transmission and prevent spread among cattle populations. We simulated RVFV transmission among cows in 22 different locations of the Kabale District in Uganda using real world livestock data in a network-based model. This model considered livestock as a spatially explicit factor in different locations subjected to specific vector and environmental factors, and was configured to investigate and quantitatively evaluate the relative impacts of mosquito control, livestock movement, and diversity in cattle populations on the spread of the RVF epizootic. We concluded that cattle movement should be restricted for periods of high mosquito abundance to control epizootic spreading among locations during an RVF outbreak. Importantly, simulation results also showed that cattle populations with heterogeneous genetic diversity as crossbreeds were less susceptible to infection compared to homogenous cattle populations.

First Laboratory-Confirmed Outbreak of Human and Animal Rift Valley Fever Virus in Uganda in 48 Years.

In March 2016, an outbreak of Rift Valley fever (RVF) was identified in Kabale district, southwestern Uganda. A comprehensive outbreak investigation was initiated, including human, livestock, and mosquito vector investigations. Overall, four cases of acute, nonfatal human disease were identified, three by RVF virus (RVFV) reverse transcriptase polymerase chain reaction (RT-PCR), and one by IgM and IgG serology. Investigations of cattle, sheep, and goat samples from homes and villages of confirmed and probable RVF cases and the Kabale central abattoir found that eight of 83 (10%) animals were positive for RVFV by IgG serology; one goat from the home of a confirmed case tested positive by RT-PCR. Whole genome sequencing from three clinical specimens was performed and phylogenetic analysis inferred the relatedness of 2016 RVFV with the 2006-2007 Kenya-2 clade, suggesting previous introduction of RVFV into southwestern Uganda. An entomological survey identified three of 298 pools (1%) of Aedes and Coquillettidia species that were RVFV positive by RT-PCR. This was the first identification of RVFV in Uganda in 48 years and the 10th independent viral hemorrhagic fever outbreak to be confirmed in Uganda since 2010.

Multisectoral prioritization of zoonotic diseases in Uganda, 2017: A One Health perspective.

BACKGROUND: Zoonotic diseases continue to be a public health burden globally. Uganda is especially vulnerable due to its location, biodiversity, and population. Given these concerns, the Ugandan government in collaboration with the Global Health Security Agenda conducted a One Health Zoonotic Disease Prioritization Workshop to identify zoonotic diseases of greatest national concern to the Ugandan government. MATERIALS AND METHODS: The One Health Zoonotic Disease Prioritization tool, a semi-quantitative tool developed by the U.S. Centers for Disease Control and Prevention, was used for the prioritization of zoonoses. Workshop participants included voting members and observers representing multiple government and non-governmental sectors. During the workshop, criteria for prioritization were selected, and questions and weights relevant to each criterion were determined. We used a decision tree to provide a ranked list of zoonoses. Participants then established next steps for multisectoral engagement for the prioritized zoonoses. A sensitivity analysis demonstrated how criteria weights impacted disease prioritization. RESULTS: Forty-eight zoonoses were considered during the workshop. Criteria selected to prioritize zoonotic diseases were (1) severity of disease in humans in Uganda, (2) availability of effective control strategies, (3) potential to cause an epidemic or pandemic in humans or animals, (4) social and economic impacts, and (5) bioterrorism potential. Seven zoonotic diseases were identified as priorities for Uganda: anthrax, zoonotic influenza viruses, viral hemorrhagic fevers, brucellosis, African trypanosomiasis, plague, and rabies. Sensitivity analysis did not indicate significant changes in zoonotic disease prioritization based on criteria weights. DISCUSSION: One Health approaches and multisectoral collaborations are crucial to the surveillance, prevention, and control strategies for zoonotic diseases. Uganda used such an approach to identify zoonoses of national concern. Identifying these priority diseases enables Uganda's National One Health Platform and Zoonotic Disease Coordination Office to address these zoonoses in the future with a targeted allocation of resources.