Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda.

IMPORTANCE: Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks.

A public, cross-reactive glycoprotein epitope confounds Ebola virus serology.

Ebola disease (EBOD) in humans is a severe disease caused by at least four related viruses in the genus Orthoebolavirus, most often by the eponymous Ebola virus. Due to human-to-human transmission and incomplete success in treating cases despite promising therapeutic development, EBOD is a high priority in public health research. Yet despite almost 50 years since EBOD was first described, the sources of these viruses remain undefined and much remains to be understood about the disease epidemiology and virus emergence and spread. One important approach to improve our understanding is detection of antibodies that can reveal past human infections. However, serosurveys routinely describe seroprevalences that imply infection rates much higher than those clinically observed. Proposed hypotheses to explain this difference include existence of common but less pathogenic strains or relatives of these viruses, misidentification of EBOD as something else, and a higher proportion of subclinical infections than currently appreciated. The work presented here maps B-cell epitopes in the spike protein of Ebola virus and describes a single epitope that is cross-reactive with an antigen seemingly unrelated to orthoebolaviruses. Antibodies against this epitope appear to explain most of the unexpected reactivity towards the spike, arguing against common but unidentified infections in the population. Importantly, antibodies of cross-reactive donors from within and outside the known EBOD geographic range bound the same epitope. In light of this finding, it is plausible that epitope mapping enables broadly applicable specificity improvements in the field of serology.

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

BACKGROUND: Rift 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. METHODS: Between 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. RESULTS: Overall, 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. CONCLUSION: RVF 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.

Knowledge, perceptions, and exposure to bats in communities living around bat roosts in Bundibugyo district, Uganda: implications for viral haemorrhagic fever prevention and control.

BACKGROUND: Bats are a reservoir for many viruses causing haemorrhagic fevers. Proximity to bats is a risk factor for virus spillover to animals and humans. We conducted this study to assess knowledge, perceptions, and exposure to bats in communities living near bat roosts in Bundibugyo District, Uganda. METHODS: A cross-sectional study using mixed methods with both quantitative and qualitative data was conducted between September and December 2022. Participants for the quantitative data (survey) (n = 384) resided near bat caves and/or roost sites and were selected using multistage random sampling. The survey investigated participants' prior exposure to bats, as well as knowledge and perceptions of bat exposure. Logistic regression was used to determine factors associated with bat exposure. Participants for the qualitative data (focus group discussions) (n = 10, 6-8 participants each) were purposely selected based on engagement in guano mining, hunting, and farming activities. Perceived risk associated with bat-related activities were identified and ranked in the focus group discussions using participatory epidemiology tools. RESULTS: In total, (214/384, 55.7%) had a history of bat exposure and (208/384, 54.2%) had poor knowledge of risk factors associated with bat exposure. Increased exposure to bats was associated with being male (OR = 1.6; 95% CI: 1.0, 2.4 p-value = 0.038), staying in urban areas (OR = 1.9; p-value = 0.010), hunting (OR = 10.9; p-value = 0.024), and positive perception to bat guano being safe as fertiliser (OR = 2.5; p-value = 0.045). During the proportional piling process, a total of 7 risk factors were identified by 10 groups with hunting during an outbreak and consumption of bats being the most frequently identified. Overall, there was a strong statistical agreement in the ranking across the 10 focus groups (W = 0.52; p < 0.01; n = 10). Based on the provided data, the adjusted odds ratio of 0.7 for the good measures (p-value = 0.112), suggests a potential protective effect on the risk of bat exposure. CONCLUSION: Communities living around bat roosts frequently come into contact with bats, yet there is inadequate awareness regarding the behaviors that can lead to the transmission of bat- borne diseases to humans. It is essential to undertake educational initiatives and preventive measures to minimise the risks of bat-related infections. The need for targeted health communication and education efforts to address these knowledge gaps and promote an accurate understanding of bats and disease transmission. Understanding of diseases associated with bats will minimize bat-related health risks especially in communities engaged in wildlife hunting.

Crimean-Congo Hemorrhagic Fever Outbreak in Refugee Settlement during COVID-19 Pandemic, Uganda, April 2021.

Crimean-Congo hemorrhagic fever (CCHF) was detected in 2 refugees living in a refugee settlement in Kikuube district, Uganda. Investigations revealed a CCHF IgG seroprevalence of 71.3% (37/52) in goats within the refugee settlement. This finding highlights the need for a multisectoral approach to controlling CCHF in humans and animals in Uganda.

Rift Valley Fever Outbreak during COVID-19 Surge, Uganda, 2021.

Rift Valley fever, endemic or emerging throughout most of Africa, causes considerable risk to human and animal health. We report 7 confirmed Rift Valley fever cases, 1 fatal, in Kiruhura District, Uganda, during 2021. Our findings highlight the importance of continued viral hemorrhagic fever surveillance, despite challenges associated with the COVID-19 pandemic.

A retrospective cohort investigation of seroprevalence of Marburg virus and ebolaviruses in two different ecological zones in Uganda.

BACKGROUND: Uganda has experienced seven Ebola Virus Disease (EVD) outbreaks and four Marburg Virus Disease (MVD) outbreaks between 2000 and 2019. We investigated the seroprevalence and risk factors for Marburg virus and ebolaviruses in gold mining communities around Kitaka gold mine in Western Uganda and compared them to non-mining communities in Central Uganda. METHODS: A questionnaire was administered and human blood samples were collected from three exposure groups in Western Uganda (gold miners, household members of miners, non-miners living within 50 km of Kitaka mine). The unexposed controls group sampled was community members in Central Uganda far away from any gold mining activity which we considered as low-risk for filovirus infection. ELISA serology was used to analyse samples, detecting IgG antibodies against Marburg virus and ebolaviruses (filoviruses). Data were analysed in STATA software using risk ratios and odds ratios. RESULTS: Miners in western Uganda were 5.4 times more likely to be filovirus seropositive compared to the control group in central Uganda (RR = 5.4; 95% CI 1.5-19.7) whereas people living in high-risk areas in Ibanda and Kamwenge districts were 3.6 more likely to be seropositive compared to control group in Luweeero district (RR = 3.6; 95% CI 1.1-12.2). Among all participants, filovirus seropositivity was 2.6% (19/724) of which 2.3% (17/724) were reactive to Sudan virus only and 0.1% (1/724) to Marburg virus. One individual seropositive for Sudan virus also had IgG antibodies reactive to Bundibugyo virus. The risk factors for filovirus seropositivity identified included mining (AOR = 3.4; 95% CI 1.3-8.5), male sex (AOR = 3.1; 95% CI 1.01-9.5), going inside mines (AOR = 3.1; 95% CI 1.2-8.2), cleaning corpses (AOR = 3.1; 95% CI 1.04-9.1) and contact with suspect filovirus cases (AOR = 3.9, 95% CI 1.04-14.5). CONCLUSIONS: These findings indicate that filovirus outbreaks may go undetected in Uganda and people involved in artisan gold mining are more likely to be exposed to infection with either Marburg virus or ebolaviruses, likely due to increased risk of exposure to bats. This calls for active surveillance in known high-risk areas for early detection and response to prevent filovirus epidemics.

Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.

In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.

Prevalence, antimicrobial susceptibility and risk factors associated with non-typhoidal Salmonella on Ugandan layer hen farms.

BACKGROUND: Non-typhoidal Salmonella (NTS) are among the leading global foodborne pathogens and a significant public health threat. Their occurrence in animal reservoirs and their susceptibilities to commonly used antimicrobials are poorly understood in developing countries. The aim of this study was to estimate the prevalence, determine antimicrobial susceptibility and identify risk factors associated with NTS presence in laying hen farms in Uganda through a cross-sectional study. RESULTS: Pooled faecal samples were collected from 237 laying hen farms and these were analysed for NTS following standard laboratory procedures. In total, 49 farms (20.7%; 95% Confidence interval (CI): 15.6-25.6%) were positive for NTS presence. Altogether, ten Salmonella serotypes were identified among the confirmed 78 isolates, and the predominant serotypes were Salmonella Newport (30.8%), S. Hadar (14.1%), S. Aberdeen (12.8%), S. Heidelberg (12.8%), and S. Bolton (12.8%). Phenotypic antimicrobial resistance was detected in 45(57.7%) of the isolates and the highest resistance was against ciprofloxacin (50.0%) followed by sulphonamides (26.9%) and sulphamethoxazole/trimethoprim (7.7%). Resistance was significantly associated with sampled districts (p = 0.034). Resistance to three or more drugs, multi-drug resistance (MDR) was detected in 12 (15.4%) of the isolates, 9 (75%) of these were from Wakiso district. A multivariable logistic model identified large farm size (OR = 7.0; 95% CI: 2.5-19.8) and the presence of other animal species on the farm (OR = 5.9; 95% CI: 2.1-16.1) as risk factors for NTS prevalence on farms. Having a separate house for birds newly brought to the farms was found to be protective (OR = 0,4; 95% CI: 0.2-0.8). CONCLUSION: This study has highlighted a high prevalence and diversity of NTS species in laying hen farms in Uganda and identified associated risk factors. In addition, it has demonstrated high levels of antimicrobial resistance in isolates of NTS. This could be because of overuse or misuse of antimicrobials in poultry production. Also importantly, the insights provided in this study justifies a strong case for strengthening One Health practices and this will contribute to the development of NTS control strategies at local, national and international levels.

Notes from the Field: Rift Valley Fever Response - Kabale District, Uganda, March 2016.

On March 9, 2016, a male butcher from Kabale District, Uganda, aged 45 years, reported to the Kabale Regional Referral Hospital with fever, fatigue, and headache associated with black tarry stools and bleeding from the nose. One day later, a student aged 16 years from a different sub-county in Kabale District developed similar symptoms and was admitted to the same hospital. The student also had a history of contact with livestock. Blood specimens collected from both patients were sent for testing for Marburg virus disease, Ebola virus disease, Rift Valley fever (RVF), and Crimean Congo Hemorrhagic fever at the Uganda Virus Research Institute, as part of the viral hemorrhagic fevers surveillance program. The Uganda Virus Research Institute serves as the national viral hemorrhagic fever reference laboratory and hosts the national surveillance program for viral hemorrhagic fevers, in collaboration with the CDC Viral Special Pathogens Branch and the Uganda Ministry of Health.

How severe and prevalent are Ebola and Marburg viruses? A systematic review and meta-analysis of the case fatality rates and seroprevalence.

BACKGROUND: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24-100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases. METHODS: Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA. RESULTS: The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0-76.0%), I2 = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5-80.0%, I2 = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%-11.0%, I2 = 98.7%), whereas that for Marburg virus was 1.2% (0.5-2.0%, I2 = 94.8%). The most severe species of ebolavirus was Zaire ebolavirus while Bundibugyo Ebolavirus was the least severe. CONCLUSIONS: The pooled CFR and seroprevalence for Ebola and Marburg viruses were found to be lower than usually reported, with species differences despite high heterogeneity between studies. Countries with an improved health surveillance and epidemic response have lower CFR, thereby indicating need for improving early detection and epidemic response in filovirus outbreaks.

Multidistrict Outbreak of Marburg Virus Disease-Uganda, 2012.

In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection.

Bat-Borne Pathogens and Public Health in Rural African Artisanal Gold Mines.

Marburg virus, the first filovirus discovered and a close cousin to the Ebola virus, is carried by the Egyptian rousette bat, a common cave-dwelling fruit bat endemic to sub-Saharan Africa whose populations can exceed 50 000 individuals. Community outbreaks of Marburg virus can result in high morbidity rates. In eastern Africa, favorite habitats of these bats include rural subterranean gold mines-sometimes worked illegally-that create environments conducive to zoonotic virus transmission. This commentary on a case describes how outbreaks of Marburg virus disease among people exposed to sub-Saharan African caves and mines containing these bats cause tensions among miners, companies, public health officials, and conservationists.

Antimicrobial susceptibility profiles of Staphylococcus aureus in cattle and humans in farming communities of Isingiro and Kamuli districts, Uganda.

Bacterial resistance to antimicrobials is fast becoming a big challenge as resistance to multiple drugs is rising rapidly. The emergence of resistant Staphylococcus aureus worldwide is life-threatening in both humans and animals and yet little is known about the burden of antimicrobial resistance (AMR) in developing countries including Uganda. Therefore, the aims of this study were to determine the prevalence of antimicrobial resistant S. aureus among humans and animals as well as assess the perceptions and practices of farmers in Kamuli and Isingiro districts in Uganda regarding AMR of S. aureus. A cross-sectional study was conducted between July and September 2020 in 147 randomly selected cattle-keeping households in Isingiro and Kamuli districts. A structured questionnaire uploaded in the Kobo-collect online data collection tool was used to assess farmers' perceptions and practices pertaining to AMR in each of the selected households. Nasal swabs (n = 147) were collected from both cattle and humans (farmers). Bacterial isolation and confirmation was done using Gram-staining and biochemical tests. This was followed by antimicrobial susceptibility testing (AST) using the Kirby Bauer disc diffusion method. Only 14/147 (9.5%) cattle samples and 45/147(30.6%) human samples tested positive for S. aureus. All cattle S. aureus isolates were resistant to Nitroimidazoles while 92.9% were resistant to Penicillins. None of the isolates were resistant to Fluoroquinolones and Aminoglycosides. All the 14 isolates exhibited AMR to at least one of the assessed antibiotics and 92.9% (13/14) showed evidence of multidrug resistance (MDR). Likewise, S. aureus human isolates showed high levels of resistance to Nitroimidazoles (100%) and Penicillins (93.3%), with none of the isolates having resistance to Aminoglycosides, and only one exhibiting resistance to Fluoroquinolones (2.2%). All the 45 human isolates exhibited AMR to at least one antibiotic while 93% (42/45) had MDR. Most farmers had good perceptions of AMR, with a significantly higher proportion of respondents from Isingiro than Kamuli showing a better understanding of AMR. Antibiotic prophylaxis was reported to be the least practiced measure of diseases and parasites control (17.0%), with more farmers in Isingiro (33.3%) undertaking it than those in Kamuli (1.3%) (p < 0.001). Penicillins and Nitroimidazoles were reported to be the most used antibiotics among cattle and humans. This study provides evidence of occurrence of S. aureus resistance to antimicrobials commonly used in both humans and livestock in Isingiro and Kamuli districts. Farmers had good perceptions regarding AMR as well as good antimicrobial use practices which can form a basis for mitigation of AMR.

Widening geographic range of Rift Valley fever disease clusters associated with climate change in East Africa.

Background: Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterizing recent RVF disease events in East Africa. Methods: Data on 100 disease events (2008 - 2022) from Kenya, Uganda, and Tanzania were obtained from public databases and institutions, and modeled against possible geo-ecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalized difference vegetation index (NDVI), livestock production system, land-use change, and long-term climatic variations. Decadal climatic variations between 1980-2022 were evaluated for association with the changing disease pattern. Results: Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1-3) and 3 livestock cases (IQR, 2-7). These clusters exhibited minimal human mortality (IQR 0-1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geo-ecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1oC increase in temperature and 1-unit increase in NDVI, 1-3 months prior were associated with increased RVF incidence rate ratios (IRR) of 1.20 (95% CI 1.1,1.2) and 9.88 (95% CI 0.85, 119.52), respectively. Long-term climatic trends showed significant decadal increase in annual mean temperature (0.12 to 0.3oC/decade, P<0.05), associated with decreasing rainfall in arid and semi-arid lowlands but increasing rainfall trends in highlands (P<0.05). These hotter and wetter highlands showed increasing frequency of RVF clusters, accounting for 76% and 43% in Uganda and Kenya, respectively. Conclusion: These findings demonstrate the changing epidemiology of RVF disease. The widening geographic range of disease is associated with climatic variations, with the likely impact of wider dispersal of virus to new areas of endemicity and future epidemics. Key questions: What is already known on this topic?: Rift Valley fever is recognized for its association with heavy rainfall, flooding, and El Niño rains in the East African region. A growing body of recent studies has highlighted a shifting landscape of the disease, marked by an expanding geographic range and an increasing number of small RVF clusters.What this study adds: This study challenges previous beliefs about RVF, revealing that it predominantly occurs in small clusters rather than large outbreaks, and its association with El Niño is not as pronounced as previously thought. Over 65% of these clusters are concentrated in the highlands of Kenya and Uganda, with 35% occurring in previously unaffected regions, accompanied by an increase in temperature and total rainfall between 1980 and 2022, along with a rise in the annual number of rainy days. Notably, the observed rainfall increases are particularly significant during the short-rains season (October-December), aligning with a secondary peak in RVF incidence. In contrast, the lowlands of East Africa, where typical RVF epidemics occur, display smaller and more varied trends in annual rainfall.How this study might affect research, practice, or policy: The worldwide consequence of the expanding RVF cluster is the broader dispersion of the virus, leading to the establishment of new regions with virus endemicity. This escalation heightens the risk of more extensive extreme-weather-associated RVF epidemics in the future. Global public health institutions must persist in developing preparedness and response strategies for such scenarios. This involves the creation and approval of human RVF vaccines and therapeutics, coupled with a rapid distribution plan through regional banks.

Widening geographic range of Rift Valley fever disease clusters associated with climate change in East Africa.

BACKGROUND: Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterising recent RVF disease events in East Africa. METHODS: Data on 100 disease events (2008-2022) from Kenya, Uganda and Tanzania were obtained from public databases and institutions, and modelled against possible geoecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalised difference vegetation index (NDVI), livestock production system, land-use change and long-term climatic variations. Decadal climatic variations between 1980 and 2022 were evaluated for association with the changing disease pattern. RESULTS: Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1-3) and three livestock cases (IQR, 2-7). These clusters exhibited minimal human mortality (IQR, 0-1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geoecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1°C increase in temperature and a 1-unit increase in NDVI, one months prior were associated with increased RVF incidence rate ratios of 1.20 (95% CI 1.1, 1.2) and 1.93 (95% CI 1.01, 3.71), respectively. Long-term climatic trends showed a significant decadal increase in annual mean temperature (0.12-0.3°C/decade, p<0.05), associated with decreasing rainfall in arid and semi-arid lowlands but increasing rainfall trends in highlands (p<0.05). These hotter and wetter highlands showed increasing frequency of RVF clusters, accounting for 76% and 43% in Uganda and Kenya, respectively. CONCLUSION: These findings demonstrate the changing epidemiology of RVF disease. The widening geographic range of disease is associated with climatic variations, with the likely impact of wider dispersal of virus to new areas of endemicity and future epidemics.

Knowledge, attitudes, and practices and long-term immune response after rVSVΔG-ZEBOV-GP Ebola vaccination in healthcare workers in high-risk districts in Uganda.

BACKGROUND: The rVSVΔG-ZEBOV-GP Ebola vaccine (rVSV-ZEBOV) has been used in response to Ebola disease outbreaks caused by Ebola virus (EBOV). Understanding Ebola knowledge, attitudes, and practices (KAP) and the long-term immune response following rVSV-ZEBOV are critical to inform recommendations on future use. METHODS: We administered surveys and collected blood samples from healthcare workers (HCWs) from seven Ugandan healthcare facilities. Questionnaires collected information on demographic characteristics and KAP related to Ebola and vaccination. IgG ELISA, virus neutralization, and interferon gamma ELISpot measured immunological responses against EBOV glycoprotein (GP). RESULTS: Overall, 37 % (210/565) of HCWs reported receiving any Ebola vaccination. Knowledge that rVSV-ZEBOV only protects against EBOV was low among vaccinated (32 %; 62/192) and unvaccinated (7 %; 14/200) HCWs. Most vaccinated (91 %; 192/210) and unvaccinated (92 %; 326/355) HCWs wanted to receive a booster or initial dose of rVSV-ZEBOV, respectively. Median time from rVSV-ZEBOV vaccination to sample collection was 37.7 months (IQR: 30.5, 38.3). IgG antibodies against EBOV GP were detected in 95 % (61/64) of HCWs with vaccination cards and in 84 % (162/194) of HCWs who reported receiving a vaccination. Geometric mean titer among seropositive vaccinees was 0.066 IU/mL (95 % CI: 0.058-0.076). CONCLUSION: As Uganda has experienced outbreaks of Sudan virus and Bundibugyo virus, for which rVSV-ZEBOV does not protect against, our findings underscore the importance of continued education and risk communication to HCWs on Ebola and other viral hemorrhagic fevers. IgG antibodies against EBOV GP were detected in most vaccinated HCWs in Uganda 2─4 years after vaccination; however, the duration and correlates of protection warrant further investigation.

Spatial prediction of Crimean Congo hemorrhagic fever virus seroprevalence among livestock in Uganda.

Crimean-Congo Hemorrhagic Fever (CCHF) is a viral disease that can infect humans via contact with tick vectors or livestock reservoirs and can cause moderate to severe disease. The first human case of CCHF in Uganda was identified in 2013. To determine the geographic distribution of the CCHF virus (CCHFV), serosampling among herds of livestock was conducted in 28 Uganda districts in 2017. A geostatistical model of CCHF seroprevalence among livestock was developed to incorporate environmental and anthropogenic variables associated with elevated CCHF seroprevalence to predict CCHF seroprevalence on a map of Uganda and estimate the probability that CCHF seroprevalence exceeded 30% at each prediction location. Environmental and anthropogenic variables were also analyzed in separate models to determine the spatially varying drivers of prediction and determine which covariate class resulted in best prediction certainty. Covariates used in the full model included distance to the nearest croplands, average annual change in night-time light index, percent sand soil content, land surface temperature, and enhanced vegetation index. Elevated CCHF seroprevalence occurred in patches throughout the country, being highest in northern Uganda. Environmental covariates drove predicted seroprevalence in the full model more than anthropogenic covariates. Combination of environmental and anthropogenic variables resulted in the best prediction certainty. An understanding of the spatial distribution of CCHF across Uganda and the variables that drove predictions can be used to prioritize specific locations and activities to reduce the risk of future CCHF transmission.