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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 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.

Following the 2013–2016 Ebola virus outbreak in West Africa, numerous groups advocated for the importance of executing clinical trials in outbreak settings. The difficulties associated with obtaining reliable data to support regulatory approval of investigational vaccines and therapeutics during that outbreak were a disappointment on a research and product development level, as well as on a humanitarian level. In response to lessons learned from the outbreak, the United States Department of Defense established a multi-institute project called the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC). JMEDICC’s primary objective is to establish the technical capability in western Uganda to execute clinical trials during outbreaks of high-consequence pathogens such as the Ebola virus. A critical component of clinical trial execution is the establishment of laboratory operations. Technical, logistical, and political challenges complicate laboratory operations, and these challenges have been mitigated by JMEDICC to enable readiness for laboratory outbreak response operations., Author summary Conducting clinical research during high-consequence pathogen outbreaks engenders complications not experienced in standard clinical research. In addition to regulatory expertise, international stakeholder engagement—including community outreach into research-naive local communities—is required, as are the technical clinical, laboratory, and infection prevention and control expertise that enables the safe and effective execution of the study in hazardous circumstances. Since the 2013–2016 Ebola virus outbreak in West Africa, researchers and public health officials alike have recognized the need to discuss these challenges. The Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC) is a unique project tasked with pre-positioning a team of highly skilled clinical researchers to execute therapeutics clinical trials during a filovirus outbreak. The project has been operating in Fort Portal, Uganda, since 2016 and is preparing to conduct clinical research if the current Ebola outbreak in the Democratic Republic of Congo spreads to Uganda. The capability is not necessarily specific for filoviruses, however, but could be utilized for high-containment clinical trial work for other high-consequence pathogens.

Introduction: Respiratory pathogens continue to present an ever increasing threat to public health (1,2). Influenza, Respiratory syncytial virus, human metapneumovirus and other respiratory viruses are major etiological agents for influenza like illnesses (ILI) (3-5). Establishment of viral causes of ILI is critical for prevention and mitigation strategies to disease threats. Makerere University Walter Reed Project (MUWRP) together with the Ugandan Ministry of Health and partners undertook surveillance to determine viral causes of influenza-like illness in Uganda. Methods: From 2008, MUWRP established hospital-based sentinel sites for surveillance activities. A total of five hospital-based sites were established, where patients aged 6 months or older presenting with ILI were enrolled. Consents were obtained as required, and a throat and/ or nasopharyngeal swab collected. Samples were screened by PCR for viral causes. Results: From October 2008 to March 2017 a total of 9,472 participants were enrolled in the study from five hospital-based surveillance sentinel sites. Majority of participants were children under 5 years n= 8,169 (86.2%). 615 (6.5%) samples tested positive for influenza A, while 385 (4.1%) tested positive for influenza B viruses and 10 (0.1%) were co-infections between influenza A and B. Of the 2,062 influenza negative samples, results indicated positivity for the following organisms; adenoviruses (9.4%), respiratory syncytial B (7.3%), parainfluenza-3 (4.5%), parainfluenza-1 (4.3%), respiratory syncytial A (3.5%), human bocavirus (1.7%), human metapneumovirus (1.7%), human coronavirus (1.5%), parainfluenza-4 (1.4%) and parainfluenza-2 (0.9%) by PCR. Conclusions: Influenza viruses account for about 11% of the causes of influenza like illness, with influenza A being the dominant type. Among the other viral causes of ILI, adenoviruses were the most dominant. Detection of other viral causes of ILI is an indication of the public health threats posed by respiratory pathogens.

BACKGROUND: Human herpesvirus 8 (HHV-8) is endemic in Uganda and transmissible by blood. We evaluated mortality following transfusion of HHV-8 antibody-positive blood. METHODS: In a hospital-based, observational, prospective cohort study with a 6-month follow-up, we examined the effect of HHV-8 antibody-positive blood on transfusion recipients surviving at least 7 days. RESULTS: Of 1092 recipients, 471 (43.1%) were transfused with HHV-8 antibody-positive blood. Median age was 1.8 years (range, 0.1-78); 111 (10.2%) died during follow-up. After adjusting for confounders (increasing age, human immunodeficiency virus infection, illness other than malaria, receipt of multiple transfusions), recipients of HHV-8 antibody-positive blood stored ≤4 days ("short-stored") were more likely to die than recipients of HHV-8 antibody-negative blood (adjusted hazards ratio [AHR], 1.92; 95% confidence interval [CI], 1.21-3.05; P = .01). The AHR of the effect of each additional short-stored HHV-8 antibody-positive transfusion was 1.79 (95% CI, 1.33-2.41; P = .001). CONCLUSIONS: Transfusion with short-stored HHV-8 antibody-positive blood was associated with an increased risk of death. Further research is warranted to determine if a causal pathway exists and to verify the observed association between acute HHV-8 infection and premature mortality.

Introduction Influenza surveillance was conducted in Uganda from October 2008 to December 2014 to identify and understand the epidemiology of circulating influenza strains in out-patient clinic attendees with influenza-like illness and inform control strategies. Methodology Surveillance was conducted at five hospital-based sentinel sites. Nasopharyngeal and/or oropharyngeal samples, epidemiological and clinical data were collected from enrolled patients. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to identify and subtype influenza strains. Data were double-entered into an Epi Info 3.5.3 database and exported to STATA 13.0 software for analysis. Results Of the 6,628 patient samples tested, influenza virus infection was detected in 10.4% (n = 687/6,628) of the specimens. Several trends were observed: influenza circulates throughout the year with two peaks; the major one from September to November and a minor one from March to June. The predominant strains of influenza varied over the years: Seasonal Influenza A(H3) virus was predominant from 2008 to 2009 and from 2012 to 2014; Influenza A(H1N1)pdm01 was dominant in 2010; and Influenza B virus was dominant in 2011. The peaks generally coincided with times of higher humidity, lower temperature, and higher rainfall. Conclusion Influenza circulated throughout the year in Uganda with two major peaks of outbreaks with similar strains circulating elsewhere in the region. Data on the circulating strains of influenza and its patterns of occurrence provided critical insights to informing the design and timing of influenza vaccines for influenza prevention in tropical regions of sub-Saharan Africa.

Live bird markets (LBMs) are essential for marketing poultry, but have been linked to many outbreaks of avian influenza (AI) and its spread. In Uganda, it has been observed that demographic characteristics of poultry traders/handlers influence activities and decision-making in LBMs. The study investigated the influence of socio-demographic characteristics of poultry handlers: age, sex, religion, educational background, level of income, location of residence and region of operation on 20 potential risk factors for introduction and spread of AI in LBMs. Study sites included 39 LBMs in the four regions of Uganda. Data was collected using a semi-structured questionnaire administered to 424 poultry handlers. We observed that background of education was a predictor for slaughter and processing of poultry in open sites. Location of residence was associated with slaughter of poultry from open sites and selling of other livestock species. Region influenced stacking of cages, inadequate cleaning of cages, feeders and drinkers, and provision of dirty feed and water. Specifically, bird handlers with secondary level of education (OR = 12.9, 95% CI: 2.88-57.4, P0.01) were more likely to be involved in open site slaughter of poultry than their counterparts without formal education. Comparatively, urbanite bird handlers were less likely to share poultry equipment (OR = 0.4, 95% CI: 0.22-0.63, P0.01) than rural resident handlers. Poultry handlers in Northern were 3.5 times more likely to practise insufficient cleaning of cages (OR = 3.5, 95% CI: 1.52-8.09) compared to those in Central region. We demonstrated that some socio-demographic characteristics of poultry handlers were predictors to risky practices for introduction and spread of AI viruses in LBMs in Uganda.

International audience; Background: Avian influenza viruses may cause severe disease in a variety of domestic animal species worldwide, with high mortality in chickens and turkeys. To reduce the information gap about prevalence of these viruses in animals in Uganda, this study was undertaken. Results: Influenza A virus prevalence by RT-PCR was 1.1% (45/4,052)while seroprevalence by ELISA was 0.8% (24/2,970). Virus prevalence was highest in domestic ducks (2.7%, 17/629) and turkeys (2.6%, 2/76), followed by free-living waterfowl (1.3%, 12/929) and swine (1.4%, 7/511). A lower proportion of chicken samples (0.4%, 7/1,865) tested positive. No influenza A virus was isolated. A seasonal prevalence of these viruses in waterfowl was 0.7% (4/561) for the dry and 2.2% (8/368) for the wet season. In poultry, prevalence was 0.2% (2/863) for the dry and 1.4% (24/1,713) for the wet season, while that of swine was 0.0% (0/159) and 2.0% (7/352) in the two seasons, respectively. Of the 45 RT-PCR positive samples, 13 (28.9%) of them were H5 but none was H7. The 19 swine sera positive for influenza antibodies by ELISA were positive for H1 antibodies by HAI assay, but the subtype(s) of ELISA positive poultry sera could not be determined. Antibodies in the poultry sera could have been those against subtypes not included in the HAI test panel. Conclusions: The study has demonstrated occurrence of influenza A viruses in animals in Uganda. The results suggest that increase in volumes of migratory waterfowl in the country could be associated with increased prevalence of these viruses in free-living waterfowl and poultry.

Capacity-building initiatives related to public health are defined as developing laboratory infrastructure, strengthening host-country disease surveillance initiatives, transferring technical expertise and training personnel. These initiatives represented a major piece of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) contributions to worldwide emerging infectious disease (EID) surveillance and response. Capacity-building initiatives were undertaken with over 80 local and regional Ministries of Health, Agriculture and Defense, as well as other government entities and institutions worldwide. The efforts supported at least 52 national influenza centers and other country-specific influenza, regional and U.S.-based EID reference laboratories (44 civilian, eight military) in 46 countries worldwide. Equally important, reference testing, laboratory infrastructure and equipment support was provided to over 500 field sites in 74 countries worldwide from October 2008 to September 2009. These activities allowed countries to better meet the milestones of implementation of the 2005 International Health Regulations and complemented many initiatives undertaken by other U.S. government agencies, such as the U.S. Department of Health and Human Services, the U.S. Agency for International Development and the U.S. Department of State.

The increasing availability of complete influenza virus genomes is deepening our understanding of influenza evolutionary dynamics and facilitating the selection of vaccine strains. However, only one complete African influenza virus sequence is available in the public domain. Here we present a complete genome analysis of 59 influenza A/H3N2 viruses isolated from humans in Uganda during the 2008 and 2009 season. Isolates were recovered from hospital-based sentinel surveillance for influenza-like illnesses and their whole genome sequenced. The viruses circulating during these two seasons clearly differed from each other phylogenetically. They showed a slow evolution away from the 2009/10 recommended vaccine strain (A/Brisbane/10/07), instead clustering with the 2010/11 recommended vaccine strain (A/Perth/16/09) in the A/Victoria/208/09 clade, as observed in other global regions. All of the isolates carried the adamantane resistance marker S31N in the M2 gene and carried several markers of enhanced transmission; as expected, none carried any marker of neuraminidase inhibitor resistance. The hemagglutinin gene of the 2009 isolates differed from that of the 2008 isolates in antigenic sites A, B, D, and to a lesser extent, C and E indicating evidence of an early phylogenetic shift from the 2008 to 2009 viruses. The internal genes of the 2009 isolates were similar to those of one 2008 isolate, A/Uganda/MUWRP-050/2008. Another 2008 isolate had a truncated PB1-F2 protein. Whole genome sequencing can enhance surveillance of future seasonal changes in the viral genome which is crucial to ensure that selected vaccine strains are protective against the strains circulating in Eastern Africa. This data provides an important baseline for this surveillance. Overall the influenza virus activity in Uganda appears to mirror that observed in other regions of the southern hemisphere.

Background Malaria and HIV are common causes of mortality in sub-Saharan Africa. The effect of HIV infection on morbidity and mortality in children with severe malarial anaemia was assessed. Methods Children Findings Of 847 children, 78 (9.2%) were HIV-infected. Median follow-up time was 162 days (inter-quartile range: 111, 169). HIV-infected children were more likely to die within 7 days (Hazard ratio [HR] = 2.86, 95% Confidence interval [CI] 1.30–6.29, P = 0.009) and within 28 days (HR = 3.70, 95% CI 1.91–7.17, P < 0.001) of an episode of severe malarial anaemia, and were more likely to die in the 6 months post-transfusion (HR = 5.70, 95% CI 3.54–9.16, P < 0.001) compared to HIV-uninfected children. HIV-infected children had more frequent re-admissions due to malaria within 28 days (Incidence rate ratio (IRR) = 3.74, 95% CI 1.41–9.90, P = 0.008) and within 6 months (IRR = 2.66, 95% CI 1.17 – 6.07, P = 0.02) post-transfusion than HIV-uninfected children. Conclusion HIV-infected children with severe malarial anaemia suffered higher all-cause mortality and malaria-related mortality than HIV-uninfected children. Children with HIV and malaria should receive aggressive treatment and further evaluation of their HIV disease, particularly with regard to cotrimoxazole prophylaxis and antiretroviral therapy.