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Background: Outbreaks are occurring at increasing frequency and they require multisectoral and multi-stakeholder involvement for optimal response. The Global Health Security Agenda is a framework that governments and other stakeholders can use to strengthen countries’ capacities to prevent, detect and respond to outbreaks but there are few examples of academic programs using this approach. Methods: This is a narrative review of contributions of Makerere University through the Global Health Security Program at the Infectious Diseases Institute (IDI). Information was sourced from peer-reviewed publications and grey literature highlighting work done between 2017 - 2021. Results: Aligned to GHSA, IDI made contributions to strengthen national and subnational capacities for biosafety and biosecurity, sample collection and transportation, electronic disease surveillance, infection prevention and control, case management prior to COVID-19 that were subsequently used to support response efforts for COVID-19 in Uganda. Conclusion: The IDI Global Health Security program provides a model that can be used by institutions to deliberately developcapacities relevant to outbreak preparedness and response. Keywords: Epidemics; University; Ebola.

ObjectivesThe emergence of multidrug-resistantNeisseria gonorrhoeae(NG) is a major global health threat necessitating response and control measures. NG antimicrobial resistance (AMR) surveillance data from sub-Saharan countries is exceedingly limited. This paper aims to describe the establishment, design and implementation of a standardised and quality-assured gonococcal surveillance programme and to describe the susceptibility patterns of the cultured gonococcal isolates in Kampala, Uganda.MethodsFrom March 2018 to September 2019, using the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) protocol, consecutive males with urethral discharge syndrome were recruited from 10 surveillance sites in Kampala City, Uganda, in collaboration with the Ministry of Health. Males completed a questionnaire and provided a urethral swab specimen. Culture, identification and antimicrobial susceptibility testing (Etest) were performed.ResultsOf the 1013 males recruited, 73.1% (740/1013) had a positive Gram stain and 51.1% (n=518) were culture-positive for NG. Using Etest (458 isolates), the resistance to ciprofloxacin was 99.6%. Most isolates were susceptible to azithromycin, cefoxitin and gentamicin, that is, 99.8%, 98.5% and 92.4%, respectively, and all isolates were susceptible to ceftriaxone and cefixime.ConclusionsWe established a standardised, quality-assured WHO EGASP. Using Etest, 458 isolates were characterised, with associated epidemiological surveillance data, in 1.5 years, which by far exceed the minimum 100 isolates per year and country requested in the WHO Global GASP, to detect AMR levels with confidence. These isolates with the epidemiological data can be used to develop population level interventions.

Uganda's proximity to the tenth Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) presents a high risk of cross-border EVD transmission. Uganda conducted preparedness and risk-mapping activities to strengthen capacity to prevent EVD importation and spread from cross-border transmission. We adapted the World Health Organization (WHO) EVD Consolidated Preparedness Checklist to assess preparedness in 11 International Health Regulations domains at the district level, health facilities, and points of entry; the US Centers for Disease Control and Prevention (CDC) Border Health Capacity Discussion Guide to describe public health capacity; and the CDC Population Connectivity Across Borders tool kit to characterize movement and connectivity patterns. We identified 40 ground crossings (13 official, 27 unofficial), 80 health facilities, and more than 500 locations in 12 high-risk districts along the DRC border with increased connectivity to the EVD epicenter. The team also identified routes and congregation hubs, including origins and destinations for cross-border travelers to specified locations. Ten of the 12 districts scored less than 50% on the preparedness assessment. Using these results, Uganda developed a national EVD preparedness and response plan, including tailored interventions to enhance EVD surveillance, laboratory capacity, healthcare professional capacity, provision of supplies to priority locations, building treatment units in strategic locations, and enhancing EVD risk communication. We identified priority interventions to address risk of EVD importation and spread into Uganda. Lessons learned from this process will inform strategies to strengthen public health emergency systems in their response to public health events in similar settings.

During the 2018-2020 Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo, risk communication and community engagement (RCCE) were prioritized in geographic areas in Uganda considered at high risk of introduction of EVD. To inform EVD preparedness in Uganda, we evaluated community perceptions and prevention practices related to EVD in 6 districts in Uganda.In March 2020, we conducted a population-based survey in 6 purposively selected districts in Uganda using multistage cluster sampling. We examined differences between districts classified as high- versus low risk for EVD in terms of their message exposure from RCCE; risk perception; and EVD knowledge, attitudes, and prevention practices.A total of 3,485 respondents were interviewed (91% response rate). EVD message exposure was more common in the high- versus low-risk districts. EVD risk perceptions were low overall but greater in the high- versus low-risk districts. Comprehensive knowledge was significantly greater in the high- versus low-risk districts (adjusted prevalence ratio [aPR] 1.61, 95% confidence interval [CI]=1.35, 1.93). Respondents' engagement in all 3 EVD prevention practices (frequent handwashing with soap, avoiding physical contact with suspected Ebola patients, and avoiding burials involving contact with a corpse) was very low (4%). However, respondents with comprehensive knowledge were more likely to engage in all 3 EVD prevention practices compared to respondents without comprehensive knowledge (aPR 1.87, 95% CI=1.08, 3.25).Our findings suggest that while RCCE efforts as part of EVD outbreak preparedness may have contributed to higher EVD knowledge in the targeted high-risk districts, uptake of prevention behaviors was similarly low across districts. In a non-outbreak setting, implementing targeted RCCE strategies may not be sufficient to motivate people to adopt protective behaviors in the absence of a high threshold of perceived threat such as in an active outbreak.

Tailoring communicable disease preparedness and response strategies to unique population movement patterns between an outbreak area and neighboring countries can help limit the international spread of disease. Global recognition of the value of addressing community connectivity in preparedness and response, through field work and visualizing the identified movement patterns, is reflected in the World Health Organization's declaration on July 17, 2019, that the 10th Ebola virus disease (Ebola) outbreak in the Democratic Republic of the Congo (DRC) was a Public Health Emergency of International Concern (1). In March 2019, the Infectious Diseases Institute (IDI), Uganda, in collaboration with the Ministry of Health (MOH) Uganda and CDC, had previously identified areas at increased risk for Ebola importation by facilitating community engagement with participatory mapping to characterize cross-border population connectivity patterns. Multisectoral participants identified 31 locations and associated movement pathways with high levels of connectivity to the Ebola outbreak areas. They described a major shift in the movement pattern between Goma (DRC) and Kisoro (Uganda), mainly through Rwanda, when Rwanda closed the Cyanika ground crossing with Uganda. This closure led some travelers to use a potentially less secure route within DRC. District and national leadership used these results to bolster preparedness at identified points of entry and health care facilities and prioritized locations at high risk further into Uganda, especially markets and transportation hubs, for enhanced preparedness. Strategies to forecast, identify, and rapidly respond to the international spread of disease require adapting to complex, dynamic, multisectoral cross-border population movement, which can be influenced by border control and public health measures of neighboring countries.

Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41 Staphylococcus aureus isolates (2017–2019). AST revealed 73 % (30 of 41) of isolates were resistant to one or more antibiotics and 29 % (12 of 41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistant S. aureus (MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24 % carriage of erm genes suggests potential for rapid development of resistance. We inferred a population structure for the S. aureus isolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitive S. aureus (MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton–Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulating S. aureus and their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.

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. CLINICALTRIAL

Tackling antimicrobial resistance (AMR) is particularly challenging in low-resource settings such as Fort Portal Regional Referral Hospital (FPRRH) in Western Uganda. Specific knowledge of local AMR epidemiology is required to inform evidence-based improvement of antibiotic stewardship measures in the hospital. To address this, we combined existing antimicrobial susceptibility testing (AST) from FPRRH, with whole genome sequencing (WGS) of 41 Staphylococcus aureus isolates (2017–2019). AST revealed 73 % (30 of 41) of isolates were resistant to one or more antibiotics and 29 % (12 of 41) were multi-drug resistant (MDR). Resistance phenotypes were largely explained by the presence of antibiotic resistance genes in WGS data. Five isolates were methicillin-resistant S. aureus (MRSA) and MDR. Although all isolates were susceptible to clindamycin, a 24 % carriage of erm genes suggests potential for rapid development of resistance. We inferred a population structure for the S. aureus isolates by comparing their core genomes. Twenty isolates formed a tight cluster corresponding to multilocus sequence typing clonal complex (CC) 152, a CC found to be particularly prevalent in northern Africa. The frequency of genes associated with methicillin, chloramphenicol and ciprofloxacin resistance were significantly lower among CC152 strains than non-CC152 strains; thus, in keeping with previous work, we find that CC152 is almost exclusively methicillin-sensitive S. aureus (MSSA). Also, in agreement with other studies, we observed that the occurrence of Panton–Valentine leukocidin toxin-encoding genes was significantly higher among CC152 strains than non-CC152 strains. However, we also observed that the coagulase gene was over-represented in this CC, further defining the virulence strategy of this important pathogen. By generating detailed information about the epidemiology of circulating S. aureus and their antibiotic susceptibility, our study has provided, for the first time, data on which evidence-based infection and AMR interventions at FPRRH can be based.

The West Africa Ebola virus disease outbreak of 2014-2016 demonstrated that responses to viral hemorrhagic fever epidemics must go beyond emergency stopgap measures and should incorporate high-quality medical care and clinical research. Optimal patient management is essential to improving outcomes, and it must be implemented regardless of geographical location or patient socioeconomic status. Coupling clinical research with improved care has a significant added benefit: Improved data quality and management can guide the development of more effective supportive care algorithms and can support regulatory approvals of investigational medical countermeasures (MCMs), which can alter the cycle of emergency response to reemerging pathogens. However, executing clinical research during outbreaks of high-consequence pathogens is complicated and comes with ethical and research regulatory challenges. Aggressive care and excellent quality control must be balanced by the requirements of an appropriate infection prevention and control posture for healthcare workers and by overcoming the resource limitations inherent in many outbreak settings. The Joint Mobile Emerging Disease Intervention Clinical Capability was established in 2015 to develop a high-quality clinical trial capability in Uganda to support rigorous evaluation of MCMs targeting high-consequence pathogens like Ebola virus. This capability assembles clinicians, laboratorians, clinical researchers, logisticians, and regulatory professionals trained in infection prevention and control and in good clinical and good clinical laboratory practices. The resulting team is prepared to provide high-quality medical care and clinical research during high-consequence outbreaks.

BACKGROUND Neisseria gonorrhoeae (commonly known as gonorrhea) has developed resistance to all first-line therapy in Southeast Asia. East Africa has historically had absent or rudimentary gonorrhea surveillance programs and, while the existence of antimicrobial-resistant gonorrhea is recognized, the extent of its resistance is largely unknown. In 2016, the World Health Organization’s Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) was initiated in Uganda to monitor resistance trends. OBJECTIVE This study characterizes gonorrhea and antibiotic resistance in a large surveillance program of men with urethral discharge syndrome from Kampala, Uganda. METHODS Men attending sentinel clinics with urethritis provided demographic information, behavior data, and a urethral swab in line with the World Health Organization’s EGASP protocols for culture, identification, and antibiotic-sensitivity testing using 2 methods—disk diffusion (Kirby-Bauer test) and Etest (BioMérieux Inc). A subset of samples underwent detailed antimicrobial resistance testing. RESULTS Of 639 samples collected from September 2016 to February 2018, 400 (62.6%) were culture-positive though 414 (64.8%) had microscopic evidence of gonorrhea. The mean age of the men from whom the samples were collected was 26.9 (SD 9.6) years and 7.2% (46/639) reported having HIV. There was high-level resistance to ciprofloxacin, tetracycline, and penicillin (greater than 90%) by Kirby-Bauer disk diffusion and 2.1% (4/188) had reduced azithromycin sensitivity by Etest. Of the early isolates that underwent detailed characterization, 60.3% (70/116) were culture-positive, 94% (66/69) isolates were either ciprofloxacin-resistant or ciprofloxacin-intermediate by Etest, 96% (65/68) were azithromycin-sensitive, and 96% (66/69) were gentamicin-sensitive. Resistance profiles were comparable between methods except for ceftriaxone (disk diffusion: 68/69, 99%; Etest: 67/69, 97%) and for gentamicin (disk diffusion: 2/8, 25%; Etest: 66/69, 96%) sensitivity. CONCLUSIONS This is the first report from a systematic gonorrhea surveillance program in Uganda. Findings demonstrated resistance or increased minimum inhibitory concentration to all key antigonococcal antibiotics. There was evidence of poor antibiotic stewardship, near-universal resistance to several antibiotics, and emerging resistance to others. Individuals in the population sampled were at exceptionally high risk of STI and HIV infection requiring intervention. Ongoing surveillance efforts to develop interventions to curtail antimicrobial-resistant gonorrhea are needed.

Background In Uganda, in the early PEPFAR era, HIV coinfections were responsible for most hospitalizations with febrile illness (as high as 85% in 2006). Currently, national guidelines recommend universal antiretroviral therapy ideally before the development of AIDS. We evaluated the prevalence of HIV among patients admitted to two regional referral hospitals with febrile illness in the era of ‘Treat All.’ Methods Participants admitted to two regional referral hospitals in Uganda were enrolled at emergency departments or medical wards. Participants uniformly received blood cultures, malaria (rapid diagnostic test), and tuberculosis (Xpert MTB/RIF Ultra), hepatitis A IgM, hepatitis B sAg, and HIV fourth generation testing were performed. Among participants with HIV, cryptococcal antigen testing and urine lipoarabinomannan (LAM) were performed. Results From August 2019-June 2020, 95 participants (58% female) with an average age of 36.2 (SD 14.1) years, presented from 11 districts in Uganda. Participants presented at facilities 4.9 days (SD: 2.5) after onset of symptoms. Additionally, 16.1% of participants had a qSOFA (quick Sepsis Related Organ Failure Assessment) severity score of 2 or greater. By 28 days, 11.0% (n=7) died and 10.8% were lost to follow-up. On admission, 25.3% (n=24) of participants had a known history of HIV, the majority (87.5%) were on ART on hospital presentation. Of the 9.5% (n=9) who were newly diagnosed with HIV during the admission 6 were started on ART during hospitalization or within a month after hospitalization. Microbiologic and rapid diagnostic test results included positive results for tuberculosis (2.1%, 2/95 PCR; 3/16 urine LAM), malaria (29.5%, 28/95), cryptococcal antigen positive (12.5%; 2/15), hepatitis A (1.1%, 1/95), and hepatitis B (5.3%, 5/95). Blood cultures were positive in 11.1% of patients (10/90) with S. pneumoniae being most common isolate (N=4). Conclusion In the universal ART era, the proportion of hospitalized febrile patients with HIV has decreased. Overall, 10% have newly diagnosed infection emphasizing the importance of continuing to test all hospitalized febrile patients. Diagnostic evaluations are needed to assess the burden of other causes of febrile illness in order to reprioritize potential differential diagnoses. Disclosures All Authors: No reported disclosures

BackgroundNeisseria gonorrhoeae (commonly known as gonorrhea) has developed resistance to all first-line therapy in Southeast Asia. East Africa has historically had absent or rudimentary gonorrhea surveillance programs and, while the existence of antimicrobial-resistant gonorrhea is recognized, the extent of its resistance is largely unknown. In 2016, the World Health Organization’s Enhanced Gonococcal Antimicrobial Surveillance Program (EGASP) was initiated in Uganda to monitor resistance trends.ObjectiveThis study characterizes gonorrhea and antibiotic resistance in a large surveillance program of men with urethral discharge syndrome from Kampala, Uganda.MethodsMen attending sentinel clinics with urethritis provided demographic information, behavior data, and a urethral swab in line with the World Health Organization’s EGASP protocols for culture, identification, and antibiotic-sensitivity testing using 2 methods—disk diffusion (Kirby-Bauer test) and Etest (BioMérieux Inc). A subset of samples underwent detailed antimicrobial resistance testing.ResultsOf 639 samples collected from September 2016 to February 2018, 400 (62.6%) were culture-positive though 414 (64.8%) had microscopic evidence of gonorrhea. The mean age of the men from whom the samples were collected was 26.9 (SD 9.6) years and 7.2% (46/639) reported having HIV. There was high-level resistance to ciprofloxacin, tetracycline, and penicillin (greater than 90%) by Kirby-Bauer disk diffusion and 2.1% (4/188) had reduced azithromycin sensitivity by Etest. Of the early isolates that underwent detailed characterization, 60.3% (70/116) were culture-positive, 94% (66/69) isolates were either ciprofloxacin-resistant or ciprofloxacin-intermediate by Etest, 96% (65/68) were azithromycin-sensitive, and 96% (66/69) were gentamicin-sensitive. Resistance profiles were comparable between methods except for ceftriaxone (disk diffusion: 68/69, 99%; Etest: 67/69, 97%) and for gentamicin (disk diffusion: 2/8, 25%; Etest: 66/69, 96%) sensitivity.ConclusionsThis is the first report from a systematic gonorrhea surveillance program in Uganda. Findings demonstrated resistance or increased minimum inhibitory concentration to all key antigonococcal antibiotics. There was evidence of poor antibiotic stewardship, near-universal resistance to several antibiotics, and emerging resistance to others. Individuals in the population sampled were at exceptionally high risk of STI and HIV infection requiring intervention. Ongoing surveillance efforts to develop interventions to curtail antimicrobial-resistant gonorrhea are needed.

HIV situation in Uganda Uganda, with an estimated population of 35 million people, is a landlocked country that forms part of the East African Union member states. The country is divided into nine political regions (Figure 1), in which there are 112 administrative districts. In order to make the administration and coordination of health services more efficient, the country is further divided into 14 health regions. Uganda is classified as a high burden HIV country with an estimated 1.6 million people living with HIV/AIDS and 140 000 new cases reported annually (Table 1; Figure 1). Being one of only two countries where incidence was on the rise in 2013, HIV remains a major public health problem in Uganda. HIV prevalence varies across the country, being highest in the Central region and near urban centres and lowest in the mid-eastern and West Nile regions.

We summarize antimicrobial drug resistance (AMR) patterns from blood cultures at a tertiary hospital in Uganda. High rates of resistance to first-line antibiotic drugs were observed among Staphylococcus aureus and gram-negative organisms. Microbiology services with susceptibility testing should be strengthened to support standardized reporting of AMR data in sub-Saharan Africa.

Background Neisseria gonorrhea resistance is a growing problem in Uganda with recent data showing increasing ciprofloxacin resistance up to 100% in this population. The WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) was initiated in Uganda in September 2016 to monitor resistance trends. Methods Urethral swabs were collected from men presenting with urethral discharge to the five sentinel clinic sites from September 2016 to March 2017. Samples were transported to a reference laboratory site. Presumptive identification of N. gonorrhea was based on growth of typical appearing colonies on Thayer–Martin in 5% CO2, a positive oxidase test, and observation of Gram-negative, oxidase-positive diplococci in stained smears. Results 116 samples were received to the reference laboratory site of which 70 (60.3%) had positive growth for Neisseria gonorrhea. Mean age was 28.5 (range 17–60). Fifty-one participants (44%) reported at least one prior episode of gonorrhea and 42 (36%) reported antibiotic use within the previous 60 days. Of those with completed Etest (bioMerieux, Marcy-lÕEtoile, France) resistance profiles, 66 (96%) were ciprofloxacin-resistant or intermediate. One isolate was ceftriaxone-resistant by E-test but susceptible by disk diffusion. Conclusion Early results from implementation of a gonorrhea surveillance program in Uganda suggest high levels of resistance to ciprofloxacin (90%) by Etest and penicillin (93%) and tetracyclines (100%) by disk diffusion. Prior studies of gonococcal resistance in Uganda have noted increasing levels of resistance, particularly to ciprofloxacin which until 2010 was the recommended first-line empiric therapy for gonococcal infection in Uganda. Of note, discrepancies were occasionally noted between disk diffusion and Etest results, which requires further investigation. Ongoing surveillance efforts will be crucial to shape clinical guidelines and national policy. Disclosures All authors: No reported disclosures.