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 10^th independent viral hemorrhagic fever outbreak to be confirmed in Uganda since 2010.

Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutionary rates during persistence were either similar to or reduced relative to acute infection rates. Active EBOV replication/transcription continued during convalescence, but decreased over time, consistent with viral persistence rather than viral latency. Patterns of genetic divergence suggest a moderate relaxation of selective constraints within the sGP carboxy-terminal tail during persistent infections, but do not support widespread diversifying selection. Altogether, our data illustrate that EBOV persistence in semen, urine, and aqueous humor is not a quiescent or latent infection.

: Rift Valley fever (RVF) is a zoonotic disease of public health and economic importance. Uganda has reported sporadic outbreaks of RVF in both humans and animals across the country, especially in the southwestern part of the “cattle corridor” through an established viral hemorrhagic fever surveillance system. We report 52 human cases of laboratory-confirmed RVF from 2017 to 2020. The case fatality rate was 42%. Among those infected, 92% were males and 90% were adults (≥ 18 years). Clinical symptoms were characterized by fever (69%), unexplained bleeding (69%), headache (51%), abdominal pain (49%), and nausea and vomiting (46%). Most of the cases (95%) originated from central and western districts that are part of the cattle corridor of Uganda, where the main risk factor was direct contact with livestock (P = 0.009). Other predictors of RVF positivity were determined to be male gender (P = 0.001) and being a butcher (P = 0.04). Next-generation sequencing identified the predominant Ugandan clade as Kenya-2, observed previously across East Africa. There is need for further investigation and research into the effect and spread of this neglected tropical disease in Uganda and the rest of Africa. Control measures such as promoting vaccination and limiting animal–human transmission could be explored to reduce the impact of RVF in Uganda and globally.

: Crimean-Congo Hemorrhagic Fever (CCHF) is endemic in Uganda, yet its epidemiology remains largely uncharacterized. To better understand its occurrence within Uganda, case reports of patients hospitalized with CCHF between 2013 and 2019 were reviewed. Further, genome sequences of CCHF-positive RNA obtained during this period were determined for phylogenetic comparisons. We found that a total of 32 cases (75% males; CFR, 31.2%), aged between 9 to 68 years, were reported during the study period. Most cases were detected during July to December of each outbreak year (81.2%; P < 0.01) and were located along the “cattle corridor” (68.7%, P = 0.03). The most common presenting symptoms were fever (93.8%), hemorrhage (81.3%), headache (78.1%), fatigue (68.8%), vomiting (68.8%), and myalgia (65.6%). In five patients for whom hematological data were available, varied abnormalities were observed including thrombocytopenia, leukopenia, anemia, lymphopenia, lymphocytosis, polycythemia, and microcytosis. About 56.3% (P = 0.47) of patients reported tick bites or exposure to livestock as their potential source of infection. Person-to-person transmission was suspected for two cases. Using unbiased metagenomics, we found that the viral S- and L- segments have remained conserved in Africa 2 clade since the 1950s. In contrast, the M segment split into two geographically interspersed clades; one that belongs to Africa 2 and another that is ancestral to Africa 1 and 2. Overall, this data summarizes information on the history and clinical presentation of human CCHF in Uganda. Importantly, it identifies vulnerable populations as well as temporal and geographic regions in Uganda where surveillance and control interventions could be focused.

The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak. We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak. Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD. Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks. WHO and US Centers for Disease Control and Prevention.

Uganda established a domestic Viral Hemorrhagic Fever (VHF) testing capacity in 2010 in response to the increasing occurrence of filovirus outbreaks. In July 2018, the neighboring Democratic Republic of Congo (DRC) experienced its 10^th Ebola Virus Disease (EVD) outbreak and for the duration of the outbreak, the Ugandan Ministry of Health (MOH) initiated a national EVD preparedness stance. Almost one year later, on 10^th June 2019, three family members who had contracted EVD in the DRC crossed into Uganda to seek medical treatment. Samples were collected from all the suspected cases using internationally established biosafety protocols and submitted for VHF diagnostic testing at Uganda Virus Research Institute. All samples were initially tested by RT-PCR for ebolaviruses, marburgviruses, Rift Valley fever (RVF) virus and Crimean-Congo hemorrhagic fever (CCHF) virus. Four people were identified as being positive for Zaire ebolavirus, marking the first report of Zaire ebolavirus in Uganda. In-country Next Generation Sequencing (NGS) and phylogenetic analysis was performed for the first time in Uganda, confirming the outbreak as imported from DRC at two different time point from different clades. This rapid response by the MoH, UVRI and partners led to the control of the outbreak and prevention of secondary virus transmission.