Uganda Virus Research Institute Research Articles

Crimean-Congo hemorrhagic fever cases diagnosed during an outbreak of Sudan virus disease in Uganda, 2022-23.

In September 2022, Uganda experienced an outbreak of Sudan virus disease (SVD), mainly in central Uganda. As a result of enhanced surveillance activities for Ebola disease, samples from several patients with suspected viral hemorrhagic fever (VHF) were sent to the VHF Program at Uganda Virus Research Institute (UVRI), Entebbe, Uganda, and identified with infections caused by other viral etiologies. Herein, we report the epidemiologic and laboratory findings of Crimean-Congo hemorrhagic fever (CCHF) cases that were detected during the SVD outbreak response. Whole blood samples from VHF suspected cases were tested for Sudan virus (SUDV) by real-time reverse transcription-polymerase chain reaction (RT-PCR); and if negative, were tested for CCHF virus (CCHFV) by RT-PCR. CCHFV genomic sequences generated by metagenomic next generation sequencing were analyzed to ascertain strain relationships. Between September 2022 and January 2023, a total of 2,626 samples were submitted for VHF testing at UVRI. Overall, 13 CCHF cases (including 7 deaths; case fatality rate of 53.8%), aged 4 to 60 years, were identified from 10 districts, including several districts affected by the SVD outbreak. Four cases were identified within the Ebola Treatment Unit (ETU) at Mubende Hospital. Most CCHF cases were males engaged in livestock farming or had exposure to wildlife (n = 8; 61.5%). Among confirmed cases, the most common clinical symptoms were hemorrhage (n = 12; 92.3%), fever (n = 11; 84.6%), anorexia (n = 10; 76.9%), fatigue (n = 9; 69.2%), abdominal pain (n = 9; 69.2%) and vomiting (n = 9; 69.2%). Sequencing analysis showed that the majority of identified CCHFV strains belonged to the Africa II clade previously identified in Uganda. Two samples, however, were identified with greater similarity to a CCHFV strain that was last reported in Uganda in 1958, suggesting possible reemergence. Identifying CCHFV from individuals initially suspected to be infected with SUDV emphasizes the need for comprehensive VHF testing during filovirus outbreak responses in VHF endemic countries. Without expanded testing, CCHFV-infected patients would have posed a risk to health care workers and others while receiving treatment after a negative filovirus diagnosis, thereby complicating response dynamics. Additionally, CCHFV-infected cases could acquire an Ebola infection while in the ETU, and upon release because of a negative Ebola virus result, have the potential to spread these infections in the community.

Job Satisfaction and Psychosocial Well-Being of COVID-19 Frontline Health Workers in Uganda

The COVID-19 pandemic exposed frontline healthcare workers (HCWs) to mental health problems and various challenges that impacted their job satisfaction. We explored the job satisfaction and psychosocial/mental well-being of COVID-19 frontline HCWs in Uganda. This was a mixed-methods study conducted at Mulago National Referral Hospital (MNRH), Entebbe Regional Referral Hospital (ERRH), and Uganda Virus Research Institute (UVRI). A pre-tested self-administered questionnaire and Four Focus Group Discussions (FGDs) were used for data collection. A five-point Likert scale was used for the quantitative data to measure mental well-being and job satisfaction. Bloom’s cut-off was used to categorize participants’ job satisfaction and mental well-being into good (≥80%), moderate (60% - <80%), and poor (<60%). FGDs were audio-recorded, transcribed, and analyzed thematically using NVivo version 12 software. 218 participants participated in the quantitative survey and 24 of them further participated in the FGDs. 51.4% ( n = 112) were males, aged 18 to 39 years (77.5%, n = 169) and 50.9% ( n = 111) were at MNRH. Overall, 54%, 28%, and 18% of the participants reported moderate, good, and poor job satisfaction respectively. Satisfaction with salary (2.6 ± 1.2) and compensation (risk) allowances (2.4 ± 1.3) was particularly low. Furthermore, 35%, 33%, and 32% of the participants reported moderate, good, and poor mental well-being respectively. Anxiety, burnout, stigma, and discrimination contributed to poor psychosocial/mental well-being. Less than half of the frontline HCWs reported good job satisfaction and psychosocial/mental well-being. There is a need for prioritization of the psychosocial well-being of frontline HCWs, in addition to improvement of remuneration systems.

Protocol for a discrete choice experiment: understanding preferences for seeking health services for survivors of sexual violence in Uganda

IntroductionSexual violence is a significant public health concern with severe physical, social and psychological consequences, which can be mitigated by health service utilisation. However, in Uganda and much of sub-Saharan...

Integrated community-based management of HIV, diabetes, and hypertension in Tanzania and Uganda: protocol for a cluster-randomized trial

Background In response to the growing burden of chronic diseases in sub-Saharan Africa, where innovative and cost-effective health solutions are imperative, this study outlines a protocol for a cluster-randomized trial that compares integrated community-based care with integrated facility-based care to improve access and outcomes for patients with HIV, diabetes, or hypertension. Methods & analysis We will conduct a pragmatic cluster-randomized trial comparing integrated community care with integrated facility care in Tanzania and Uganda. Patients living with HIV, diabetes, or hypertension, stable on treatment in health facilities, will be organised into groups of approximately 8–14 persons and randomly assigned to integrated community or facility-based care. The study has two co-primary endpoints: a composite endpoint of glycemia and blood pressure control among individuals with diabetes and/or hypertension and suppression of plasma viral load among people living with HIV. Participants will receive their drugs, adherence support, and monitoring at a community venue in the integrated community arm. Those randomised to the control arm will receive integrated facility-based care. All study participants will be followed up for 12 months. A sample size of 116 groups will provide over 80% power to detect an absolute difference in blood pressure and blood glucose control of 10% at the 5% two-sided significance level. For HIV viral suppression, the trial will have over 80% power to show non-inferiority with a delta margin = 8.5%, 7.5%, and 5.5% assuming viral suppression is 85%, 90% and 95% respectively. To allow for loss to follow-up, our target for enrolment is 124 groups, each comprising an average of 14 participants. An economic evaluation within the trial will be conducted to estimate the cost and cost-effectiveness of integrated community care compared with integrated facility care. This will be complemented by a built-in social science process evaluation. Ethics and dissemination Ethical approval was granted by the Research Ethics Committees of the University College London (UCL), the National Institute of Medical Research (Tanzania), and the Uganda Virus Research Institute (Uganda). The findings will be disseminated through journal publications and meetings with key stakeholders. Trial registration number ISRCTN Registry: ISRCTN15319595, registration date: 07 June 2022.

Severe morbidity and hospital-based mortality from Rift Valley fever disease between November 2017 and March 2020 among humans in Uganda

BackgroundRift Valley fever (RVF) is a zoonotic viral disease of increasing intensity among humans in Africa and the Arabian Peninsula. In Uganda, cases reported prior to 2016 were mild or not fully documented. We report in this paper on the severe morbidity and hospital-based mortality of human cases in Uganda.MethodsBetween November 2017 and March 2020 human cases reported to the Uganda Virus Research Institute (UVRI) were confirmed by polymerase chain reaction (PCR). Ethical and regulatory approvals were obtained to enrol survivors into a one-year follow-up study. Data were collected on socio-demographics, medical history, laboratory tests, potential risk factors, and analysed using Stata software.ResultsOverall, 40 cases were confirmed with acute RVF during this period. Cases were not geographically clustered and nearly all were male (39/40; 98%), median age 32 (range 11–63). The median definitive diagnosis time was 7 days and a delay of three days between presumptive and definitive diagnosis. Most patients (31/40; 78%) presented with fever and bleeding at case detection. Twenty-eight (70%) cases were hospitalised, out of whom 18 (64%) died. Mortality was highest among admissions in regional referral (11/16; 69%) and district (4/5; 80%) hospitals, hospitalized patients with bleeding at case detection (17/27; 63%), and patients older than 44 years (9/9; 100%). Survivors mostly manifested a mild gastro-intestinal syndrome with nausea (83%), anorexia (75%), vomiting (75%), abdominal pain (50%), and diarrhoea (42%), and prolonged symptoms of severe disease including jaundice (67%), visual difficulties (67%), epistaxis (50%), haemoptysis (42%), and dysentery (25%). Symptom duration varied between two to 120 days.ConclusionRVF is associated with high hospital-based mortality, severe and prolonged morbidity among humans that present to the health care system and are confirmed by PCR. One-health composite interventions should be developed to improve environmental and livestock surveillance, prevent infections, promptly detect outbreaks, and improve patient outcomes.

Decentralising chronic disease management in sub-Saharan Africa: a protocol for the qualitative process evaluation of community-based integrated management of HIV, diabetes and hypertension in Tanzania and Uganda

IntroductionSub-Saharan Africa continues to experience a syndemic of HIV and non-communicable diseases (NCDs). Vertical (stand-alone) HIV programming has provided high-quality care in the region, with almost 80% of people living...

Ongoing Cooperative Engagement Facilitates Agile Pandemic and Outbreak Response: Lessons Learned Through Cooperative Engagement Between Uganda and the United States.

Pathogens threaten human lives and disrupt economies around the world. This has been clearly illustrated by the current COVID-19 pandemic and outbreaks in livestock and food crops. To manage pathogen emergence and spread, cooperative engagement programs develop and strengthen biosafety, biosecurity, and biosurveillance capabilities among local researchers to detect pathogens. In this case study, we describe the efforts of a collaboration between the Los Alamos National Laboratory and the Uganda Virus Research Institute, the primary viral diagnostic laboratory in Uganda, to implement and ensure the sustainability of sequencing for biosurveillance. We describe the process of establishing this capability along with the lessons learned from both sides of the partnership to inform future cooperative engagement efforts in low- and middle-income countries. We found that by strengthening sequencing capabilities at the Uganda Virus Research Institute before the COVID-19 pandemic, the institute was able to successfully sequence SARS-CoV-2 samples and provide data to the scientific community. We highlight the need to strengthen and sustain capabilities through in-country training, collaborative research projects, and trust.

Re-testing as a method of implementing external quality assessment program for COVID-19 real time PCR testing in Uganda.

Significant milestones have been made in the development of COVID19 diagnostics Technologies. Government of the republic of Uganda and the line Ministry of Health mandated Uganda Virus Research Institute to ensure quality of COVID19 diagnostics. Re-testing was one of the methods initiated by the UVRI to implement External Quality assessment of COVID19 molecular diagnostics. participating laboratories were required by UVRI to submit their already tested and archived nasopharyngeal samples and corresponding meta data. These were then re-tested at UVRI using the WHO Berlin protocol, the UVRI results were compared to those of the primary testing laboratories in order to ascertain performance agreement for the qualitative & quantitative results obtained. Ms Excel window 12 and GraphPad prism ver 15 was used in the analysis. Bar graphs, pie charts and line graphs were used to compare performance agreement between the reference Laboratory and primary testing Laboratories. Eleven (11) Ministry of Health/Uganda Virus Research Institute COVID19 accredited laboratories participated in the re-testing of quality control samples. 5/11 (45%) of the primary testing laboratories had 100% performance agreement with that of the National Reference Laboratory for the final test result. Even where there was concordance in the final test outcome (negative or positive) between UVRI and primary testing laboratories, there were still differences in CT values. The differences in the Cycle Threshold (CT) values were insignificant except for Tenna & Pharma Laboratory and the UVRI(p = 0.0296). The difference in the CT values were not skewed to either the National reference Laboratory(UVRI) or the primary testing laboratory but varied from one laboratory to another. In the remaining 6/11 (55%) laboratories where there were discrepancies in the aggregate test results, only samples initially tested and reported as positive by the primary laboratories were tested and found to be false positives by the UVRI COVID19 National Reference Laboratory. False positives were detected from public, private not for profit and private testing laboratories in almost equal proportion. There is need for standardization of molecular testing platforms in Uganda. There is also urgent need to improve on the Laboratory quality management systems of the molecular testing laboratories in order to minimize such discrepancies.

Community engagement in genetics and genomics research: a qualitative study of the perspectives of genetics and genomics researchers in Uganda

BackgroundGenerally, there is unanimity about the value of community engagement in health-related research. There is also a growing tendency to view genetics and genomics research (GGR) as a special category of research, the conduct of which including community engagement (CE) as needing additional caution. One of the motivations of this study was to establish how differently if at all, we should think about CE in GGR.AimTo assess the perspectives of genetics and genomics researchers in Uganda on CE in GGR.MethodA cross-sectional qualitative study was conducted at Makerere University and Uganda Virus Research Institute. Twenty-five individuals participated, the majority being male (sixteen). Participants included nineteen genetics and genomics researchers (researchers and research coordinators), two CE officers, three nurses and one nursing counsellor. Data were collected using in-depth interviews and analyzed in a thematic manner using NVivo version 12 Plus.Study findingsThirteen of the respondents had conducted CE in their GGR in either a geographical and disease-specific community. Some respondents said CE principles are the same and there is no need for special consideration for CE in GGR. Others gave ethical issues in GGR that require special consideration for CE in such research and these were categorized into six themes: GGR is new to communities, Difficulty in communicating GGR by the researchers, Genes are shared in communities, Cultural sensitivities against GGR, Community attitude toward GGR, Some GGR studies take long to end, and Negotiation of research benefits. Special considerations for CE when conducting GGR were suggested and categorized into seven themes: creating awareness of GGR in communities, obtaining both community acceptance and individual consent, CE team composition, involve communities in solving GGR challenges, prolong CE in some GGR, develop guidelines for CE in GGR, and legal considerations on GGR.ConclusionGGR was characterized by special issues that require special CE considerations for such research.

Integration of SARS-CoV-2 testing and genomic sequencing into influenza sentinel surveillance in Uganda, January to December 2022.

Respiratory pathogens cause high rates of morbidity and mortality globally and have high pandemic potential. During the SARS-CoV-2 pandemic, influenza surveillance was significantly interrupted because of resources being diverted to SARS-CoV-2 testing and sequencing. Based on recommendations from the World Health Organization, the Uganda Virus Research Institute, National Influenza Center laboratory integrated SARS-CoV-2 testing and genomic sequencing into the influenza surveillance program. We describe the results of influenza and SARS-CoV-2 testing of samples collected from 16 sentinel surveillance sites located throughout Uganda as well as SARS-CoV-2 testing and sequencing in other health centers. The surveillance system showed that both SARS-CoV-2 and influenza can be monitored in communities at the national level. The integration of SARS-CoV-2 detection and genomic surveillance into the influenza surveillance program will help facilitate the timely release of SARS-CoV-2 information for COVID-19 pandemic mitigation and provide important information regarding the persistent threat of influenza.

Rift valley fever outbreak in Sembabule District, Uganda, December 2020

BackgroundRift Valley Fever (RVF) is a viral zoonosis that can cause severe haemorrhagic fevers in humans and high mortality rates and abortions in livestock. On 10 December 2020, the Uganda Ministry of Health was notified of the death of a 25-year-old male who tested RVF-positive by reverse-transcription polymerase chain reaction (RT-PCR) at the Uganda Virus Research Institute. We investigated to determine the scope of the outbreak, identify exposure factors, and institute control measures.MethodsA suspected case was acute-onset fever (or axillary temperature > 37.5 °C) and ≥ 2 of: headache, muscle or joint pain, unexpected bleeding, and any gastroenteritis symptom in a resident of Sembabule District from 1 November to 31 December 2020. A confirmed case was the detection of RVF virus nucleic acid by RT-PCR or serum IgM antibodies detected by enzyme-linked immunosorbent assay (ELISA). A suspected animal case was livestock (cattle, sheep, goats) with any history of abortion. A confirmed animal case was the detection of anti-RVF IgM antibodies by ELISA. We took blood samples from herdsmen who worked with the index case for RVF testing and conducted interviews to understand more about exposures and clinical characteristics. We reviewed medical records and conducted an active community search to identify additional suspects. Blood samples from animals on the index case’s farm and two neighbouring farms were taken for RVF testing.ResultsThe index case regularly drank raw cow milk. None of the seven herdsmen who worked with him nor his brother’s wife had symptoms; however, a blood sample from one herdsman was positive for anti-RVF-specific IgM and IgG. Neither the index case nor the additional confirmed case-patient slaughtered or butchered any sick/dead animals nor handled abortus; however, some of the other herdsmen did report high-risk exposures to animal body fluids and drinking raw milk. Among 55 animal samples collected (2 males and 53 females), 29 (53%) were positive for anti-RVF-IgG.ConclusionsTwo human RVF cases occurred in Sembabule District during December 2020, likely caused by close interaction between infected cattle and humans. A district-wide animal serosurvey, animal vaccination, and community education on infection prevention practices campaign could inform RVF exposures and reduce disease burden.

The road to a polio-free Uganda; contribution of the Expanded Program on Immunization Laboratory (EPI-LAB) at Uganda Virus Research Institute.

The control of poliomyelitis in Uganda dates back as far as 1950 and acute flaccid paralysis (AFP) surveillance has since been used as a criterion for identifying wild polioviruses. Poliovirus isolation was initially pursued through collaborative research however, in 1993, the Expanded Program on Immunization Laboratory (EPI-LAB) was established as a member of the Global Poliovirus Laboratory Network (GPLN) and spearheaded this activity at Uganda Virus Research Institute. The aim of this report is to document the progress and impact of the EPI-LAB on poliovirus eradication in Uganda. Poliovirus detection and identification were achieved fundamentally through tissue culture and intra-typic differentiation of the poliovirus based on the real-time reverse transcriptase polymerase chain reaction (rRT PCR). The data obtained was entered into the national AFP database and analysed using EpiInfoTM statistical software. Quantitative and qualitative detection of wild and Sabin polioviruses corresponded with the polio campaigns. The WHO target indicators for AFP surveillance were achieved essentially throughout the study period. Virological tracking coupled with attaining standard AFP surveillance indicators has been pivotal in achieving and maintaining the national wild polio-free status. Laboratory surveillance remains key in informing the certification process of polio eradication.

Is it feasible to implement a community-based participatory group programme to address issues of access to healthcare for people with disabilities in Luuka district Uganda? A study protocol for a mixed-methods pilot study

IntroductionOn average, people with disabilities face many difficulties in accessing healthcare and experience worse health outcomes. Yet, evidence on how to overcome these barriers is lacking. Participatory approaches are gaining...

Identification and characterisation of diabetes in Uganda: protocol for the nested, population-based ‘Diabetes in low-resource Populations’ (DOP) Study

IntroductionSub-Saharan Africa is experiencing an increasing burden of diabetes, but there are little reliable data, particularly at the community level, on the true prevalence or why this condition affects young...

Assessing knowledge, acceptability and social implications of a peer-to-peer HIV self-testing kit distribution model among adolescents aged 15–24 in Zambia and Uganda—HISTAZU: a mixed-method study protocol

IntroductionHIV self-testing (HIVST) across sub-Saharan African countries may be acceptable as it overcomes significant barriers to clinic-based HIV testing services such as privacy and confidentiality. There are a number of...

Environmental determinants of Kaposi’s sarcoma-associated herpesvirus (KSHV) transmission in rural Uganda (ENDKU study): Contributions to research on KSHV infection and reactivation in African children; A longitudinal cohort study

BackgroundThe Environmental Determinants of KSHV transmission in rural Uganda (ENDKU) study began enrollment in February 2020 with the purpose of defining the relationship between malaria, primarily caused by Plasmodium falciparum in sub-Saharan Africa, and KSHV susceptibility and reactivation. Uganda is an ideal study site, because both malaria and KSHV are endemic and widespread, even among young children. MethodsENDKU is a longitudinal cohort study of infants enrolled at six months of age and followed until three years of age. The main study, and one smaller sub-study, is nested within the General Population Cohort (GPC), a long-standing population cohort in rural Uganda. The ENDKU study was created to test the hypothesis that P. falciparum malaria increases an infant’s susceptibility to KSHV infection. A sub-study to evaluate the effects of P. falciparum on KSHV reactivation involves an additional cohort of 5–10-year-old children with and without acute malaria who presented to the GPC study clinic. For each study, participants provided demographic and behavioral data through administered questionnaires and blood and saliva samples. ResultsDespite barriers presented by the COVID-19 pandemic, the study team was able to leverage the long-standing relationship of the UK Medical Research Council and the Uganda Virus Research Institute (MRC/UVRI) with the community, a strong commitment to research, and a multi-disciplinary team of experts to successfully implement the ENDKU study. ConclusionThe results of this multi-pronged approach will answer important questions about the etiology and transmission of KSHV in sub-Saharan Africa and the data and samples collected will be an important future resource for scientific research in the region.

Household food insecurity, maternal nutrition, environmental risks and infants’ health outcomes: protocol of the IMPALA birth cohort study in Uganda

IntroductionIn low- and middle-income countries (LMICs), food insecurity and undernutrition disproportionately affect women of reproductive age, infants and young children. The disease burden from undernutrition in these vulnerable sections of...

First laboratory confirmation and sequencing of Zaire ebolavirus in Uganda following two independent introductions of cases from the 10th Ebola Outbreak in the Democratic Republic of the Congo, June 2019.

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 10th 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 10th 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.

Rapid establishment of a frontline field laboratory in response to an imported outbreak of Ebola virus disease in western Uganda, June 2019

The Democratic Republic of the Congo (DRC) declared an Ebola virus disease (EVD) outbreak in North Kivu in August 2018. By June 2019, the outbreak had spread to 26 health zones in northeastern DRC, causing >2,000 reported cases and >1,000 deaths. On June 10, 2019, three members of a Congolese family with EVD-like symptoms traveled to western Uganda’s Kasese District to seek medical care. Shortly thereafter, the Viral Hemorrhagic Fever Surveillance and Laboratory Program (VHF program) at the Uganda Virus Research Institute (UVRI) confirmed that all three patients had EVD. The Ugandan Ministry of Health declared an outbreak of EVD in Uganda’s Kasese District, notified the World Health Organization, and initiated a rapid response to contain the outbreak. As part of this response, UVRI and the United States Centers for Disease Control and Prevention, with the support of Uganda’s Public Health Emergency Operations Center, the Kasese District Health Team, the Superintendent of Bwera General Hospital, the United States Department of Defense’s Makerere University Walter Reed Project, and the United States Mission to Kampala’s Global Health Security Technical Working Group, jointly established an Ebola Field Laboratory in Kasese District at Bwera General Hospital, proximal to an Ebola Treatment Unit (ETU). The laboratory consisted of a rapid containment kit for viral inactivation of patient specimens and a GeneXpert Instrument for performing Xpert Ebola assays. Laboratory staff tested 76 specimens from alert and suspect cases of EVD; the majority were admitted to the ETU (89.3%) and reported recent travel to the DRC (58.9%). Although no EVD cases were detected by the field laboratory, it played an important role in patient management and epidemiological surveillance by providing diagnostic results in <3 hours. The integration of the field laboratory into Uganda’s National VHF Program also enabled patient specimens to be referred to Entebbe for confirmatory EBOV testing and testing for other hemorrhagic fever viruses that circulate in Uganda.

Sporadic Rift Valley Fever Outbreaks in Humans and Animals in Uganda, October 2017-January 2018.

Introduction Rift Valley fever (RVF) is a mosquito-borne viral zoonosis. The Uganda Ministry of Health received alerts of suspected viral haemorrhagic fever in humans from Kiruhura, Buikwe, Kiboga, and Mityana districts. Laboratory results from Uganda Virus Research Institute indicated that human cases were positive for Rift Valley fever virus (RVFV) by polymerase chain reaction. We investigated to determine the scope of outbreaks, identify exposure factors, and recommend evidence-based control and prevention measures. Methods A suspected case was defined as a person with acute fever onset, negative malaria test result, and at least two of the following symptoms: headache, muscle or joint pain, bleeding, and any gastroenteritis symptom (nausea, vomiting, abdominal pain, diarrhoea) in a resident of Kiruhura, Buikwe, Mityana, and Kiboga districts from 1st October 2017 to 30th January 2018. A confirmed case was defined as a suspected case with laboratory confirmation by either detection of RVF nucleic acid by reverse-transcriptase polymerase chain reaction (RT-PCR) or demonstration of serum IgM or IgG antibodies by ELISA. Community case finding was conducted in all affected districts. In-depth interviews were conducted with human cases that were infected with RVF who included herdsmen and slaughterers/meat handlers to identify exposure factors for RVF infection. A total of 24 human and 362 animal blood samples were tested. Animal blood samples were purposively collected from farms that had reported stormy abortions in livestock and unexplained death of animals after a short illness (107 cattle, 83 goats, and 43 sheep). Convenient sampling for the wildlife (10 zebras, 1 topi, and 1 impala) was conducted to investigate infection in animals from Kiruhura, Buikwe, Mityana, and Kiboga districts. Human blood was tested for anti-RVFV IgM and IgG and animal blood for anti-RVFV IgG. Environmental assessments were conducted during the outbreaks in all the affected districts. Results Sporadic RVF outbreaks occurred from mid-October 2017 to mid-January 2018 affecting humans, domestic animals, and wildlife. Human cases were reported from Kiruhura, Buikwe, Kiboga, and Mityana districts. Of the 24 human blood samples tested, anti-RVFV IgG was detected in 7 (29%) human samples; 1 human sample had detectable IgM only, and 6 had both IgM and IgG. Three of the seven confirmed human cases died among humans. Results from testing animal blood samples obtained from Kiruhura district indicated that 44% (64/146) cattle, 46% (35/76) goats, and 45% (9/20) sheep tested positive for RVF. Among wildlife, (1/10) zebras, (1/1) topi, and (1/1) impala tested positive for RVFV by serological tests. One blood sample from sheep in Kiboga district tested RVFV positive. All the human cases were exposed through contact or consumption of meat from infected animals. Conclusion RVF outbreaks occurred in humans and animals in Kiruhura, Buikwe, Mityana, and Kiboga districts. Human cases were potentially infected through contact with infected animals and their products.