On 28 March, 2016, the Ministry of Health received a report on three deaths from an unknown disease characterized by fever, jaundice, and hemorrhage which occurred within a one-month period in the same family in central Uganda. We started an investigation to determine its nature and scope, identify risk factors, and to recommend eventually control measures for future prevention. We defined a probable case as onset of unexplained fever plus ≥1 of the following unexplained symptoms: jaundice, unexplained bleeding, or liver function abnormalities. A confirmed case was a probable case with IgM or PCR positivity for yellow fever. We reviewed medical records and conducted active community case-finding. In a case-control study, we compared risk factors between case-patients and asymptomatic control-persons, frequency-matched by age, sex, and village. We used multivariate conditional logistic regression to evaluate risk factors. We also conducted entomological studies and environmental assessments. From February to May, we identified 42 case-persons (35 probable and seven confirmed), of whom 14 (33%) died. The attack rate (AR) was 2.6/100,000 for all affected districts, and highest in Masaka District (AR = 6.0/100,000). Men (AR = 4.0/100,000) were more affected than women (AR = 1.1/100,000) (p = 0.00016). Persons aged 30–39 years (AR = 14/100,000) were the most affected. Only 32 case-patients and 128 controls were used in the case control study. Twenty three case-persons (72%) and 32 control-persons (25%) farmed in swampy areas (OR_adj = 7.5; 95%CI = 2.3–24); 20 case-patients (63%) and 32 control-persons (25%) who farmed reported presence of monkeys in agriculture fields (OR_adj = 3.1, 95%CI = 1.1–8.6); and 20 case-patients (63%) and 35 control-persons (27%) farmed in forest areas (OR_adj = 3.2; 95%CI = 0.93–11). No study participants reported yellow fever vaccination. Sylvatic monkeys and Aedes mosquitoes were identified in the nearby forest areas. This yellow fever outbreak was likely sylvatic and transmitted to a susceptible population probably by mosquito bites during farming in forest and swampy areas. A reactive vaccination campaign was conducted in the affected districts after the outbreak. We recommended introduction of yellow fever vaccine into the routine Uganda National Expanded Program on Immunization and enhanced yellow fever surveillance.

Rationale: Little is known about the epidemiology of severe acute respiratory infection (SARI) or influenza in sub-Saharan Africa. Characterization of influenza transmission dynamics and risk factors for severe disease and mortality is critical to inform prevention and mitigation strategies. Objectives: To characterize the epidemiology and transmission dynamics of influenza and risk factors for influenza-associated severe respiratory infection in Uganda. Methods: Clinicians at 12 sentinel surveillance sites prospectively collected clinical data and upper respiratory tract samples from consecutive patients who met criteria for SARI and influenza-like illness (ILI). Samples were tested for influenza A and B viruses using real-time reverse transcription–polymerase chain reaction. Spatial and spatiotemporal cluster modeling was performed to identify loci of increased influenza transmission. Morbidity and mortality were assessed through chart review in a defined subset of patients. Univariable and multivariable analyses were used to identify risk factors for severe respiratory infection, prolonged hospitalization, and in-hospital mortality. Measurements and Main Results: From October 2010 to June 2015, 9,978 patients met case definitions for SARI and ILI and had samples tested for influenza A and B. Of the 9,978 patient samples tested, 1,113 (11.2%) were positive for influenza. Among 6,057 patients with ILI, 778 samples (12.8%) were positive, and among 3,921 patients with SARI, 335 samples (8.5%) were positive. Significant clustering of influenza cases was observed in urban and periurban areas and during rainy seasons. Among 1,405 cases of SARI with available outcome data, in-hospital mortality was 1.6%. Infection with the 2009 pandemic A/H1N1 subtype and prolonged time to presentation were independently associated with SARI among influenza cases. Conclusions: Influenza is associated with a substantial proportion of acute respiratory infection in Uganda. As influenza vaccination programs are developed in East Africa, timing campaigns to confer protection during rainy seasons should be considered, particularly among high-risk urban populations.

Zika virus (ZIKV), transmitted by Aedes species mosquitoes, was first isolated in Uganda in 1947. From February 2014 to October 2017, the Uganda Virus Research Institute, in collaboration with the US Centers for Diseases Control and Prevention, conducted arbovirus surveillance in acute febrile illness (AFI) patients at St Francis hospital in Nkonkonjeru. Three hundred and eighty-four serum samples were collected and tested for IgM antibodies to yellow fever virus (YFV), West Nile virus (WNV), dengue virus (DENV), chikungunya virus (CHIKV) and ZIKV. Of the 384 samples, 5 were positive for ZIKV IgM. Of these five, three were confirmed by plaque reduction neutralization test (PRNT) to be ZIKV infections. Of the remaining two, one was determined to be a non-specific flavivirus infection and one was confirmed to be alphavirus-positive by reverse transcriptase polymerase chain reaction (RT-PCR). This study provides the first evidence of laboratory-confirmed ZIKV infection in Uganda in five decades, and emphasizes the need to enhance sentinel surveillance.

: Among a prospective cohort of children and adults admitted to a national COVID-19 treatment unit in Uganda from March to December 2020, we characterized the epidemiology of and risk factors for severe illness. Across two epidemic phases differentiated by varying levels of community transmission, the proportion of patients admitted with WHO-defined severe COVID-19 ranged from 5% (7/146; 95% CI: 2–10) to 33% (41/124; 95% CI: 25–42); 21% (26/124; 95% CI: 14–29%) of patients admitted during the peak phase received oxygen therapy. Severe COVID-19 was associated with older age, male sex, and longer duration of illness before admission. Coinfection with HIV was not associated with illness severity; malaria or tuberculosis coinfection was rare. No patients died during admission. Despite low mortality, hospital incidence of severe COVID-19 during the first epidemic peak in Uganda was substantial. Improvements in vaccine deployment and acute care capacity, including oxygen delivery, are urgently needed to prevent and manage severe COVID-19 in sub-Saharan Africa.

: The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.