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.

Self-Care Practices and the Associated Socio-Demographic Variables of Persons With Type 2 Diabetes Mellitus (T2dm) in Southeast, Nigeria.

Objective: The study was aimed at assessing the self-care practices and the associated socio-demographic variables of persons with T2DM in South East, Nigeria. Methodology: A cross-sectional study involving 382 persons with T2DM proportionately selected from 4 tertiary health institutions in South Eastern, Nigeria. Data was collected using the Summary of Diabetes Self-Care Activities (SDSCA) and a researcher-developed questionnaire. The questionnaire was administered to persons with T2DM who attended a diabetic outpatient clinic. Data collected was analyzed in frequency percentage. Responses on SDSCA were ranked and rated as poor, moderate, and good self-care behavior. The level of significance was placed at P < .05. Result: The majority of the participants were within the age groups of 40 to 59 (46.9%) and 60 and above (46.9%); the majority (74.6%) were married while a good proportion were traders (59.7%). Also, the majority of participants (81.2%) were on oral hypoglycemic agents. Findings further showed that a good proportion (51.3% and 89.8%) of study participants had good self-care behavior in diet and medication domains respectively. Whereas the proportion of participants with poor self-care behavior was very high in foot care (75.1%) and fairly high in both self-blood sugar testing (37.7%) and exercise (37.2%) domains. Only 7.9% practiced 3-monthly laboratory blood glucose testing while 16.5% went for eye checks every 6 months. Conclusion: Individuals with diabetes mellitus have poor self-management behavior in most domains of the self-management practice. Age, gender, marital status, educational level, and occupation significantly influenced self-management practices. Hence nurses and health educators should take diabetes self-management education very seriously to help diabetes sufferers improve their self-management behavior.

Seroepidemiological investigation of Crimean Congo hemorrhagic fever virus in livestock in Uganda, 2017.

Crimean-Congo Hemorrhagic fever (CCHF) is an important zoonotic disease transmitted to humans both by tick vectors and contact with fluids from an infected animal or human. Although animals are not symptomatic when infected, they are the main source of human infection. Uganda has reported sporadic human outbreaks of CCHF in various parts of the country since 2013. We designed a nationwide epidemiological study to investigate the burden of CCHF in livestock. A total of 3181 animals were sampled; 1732 cattle (54.4%), 1091 goats (34.3%), and 358 sheep (11.3%) resulting in overall livestock seropositivity of IgG antibodies against CCHF virus (CCHFV) of 31.4% (999/3181). Seropositivity in cattle was 16.9% and in sheep and goats was 48.8%. Adult and juvenile animals had higher seropositivity compared to recently born animals, and seropositivity was higher in female animals (33.5%) compared to male animals (24.1%). Local breeds had higher (36.8%) compared to exotic (2.8%) and cross breeds (19.3%). Animals that had a history of abortion or stillbirth had higher seropositivity compared to those without a history of abortion or stillbirth. CCHFV seropositivity appeared to be generally higher in northern districts of the country, though spatial trends among sampled districts were not examined. A multivariate regression analysis using a generalized linear mixed model showed that animal species, age, sex, region, and elevation were all significantly associated with CCHFV seropositivity after adjusting for the effects of other model predictors. This study shows that CCHFV is actively circulating in Uganda, posing a serious risk for human infection. The results from this study can be used to help target surveillance efforts for early case detection in animals and limit subsequent spillover into humans.

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 Countrywide Seroepidemiological Survey of Rift Valley Fever in Livestock, Uganda, 2017.

In 2016, an outbreak of Rift Valley fever was reported in the Kabale District in Uganda for the first time in 48 years. Three human cases were confirmed by polymerase chain reaction, and subsequent serological investigations revealed an overall IgG seropositivity of 13% in humans and 13% in animals. In response to this reemergence, we designed a countrywide survey to determine the seropositivity of anti-Rift Valley fever virus (RVFV) IgG antibodies in livestock. Samples were collected from 27 districts and tested for RVFV anti-IgG antibodies. A total of 3,181 livestock samples were tested, of which 54.4% were cattle (1,732 of 3,181), 34.3% were goats (1,091 of 3,181), and 11.3% were sheep (358 of 3,181). Overall RVFV seropositivity was 6.9% (221 of 3,181). Seroprevalence was greater in cattle (10.7%) compared with goats (2.6%) and sheep (2.0%), among females (7.5%) compared with males (5.2%), and among adults (7.6%) compared with juveniles (4.9%) and nurslings (6.4%). Exotic breeds and animals with a history of abortion or stillbirth also had greater odds of RVFV seropositivity. Animals grazed under tethering and paddocking had greater RVFV seropositivity compared with animals that grazed communally, and livestock in the western and eastern regions had the greatest seroprevalence. In a multivariate regression model, animal species (odds ratio [OR], 6.4; 95% CI, 3.5-11.4) and age (OR, 2.3; 95% CI, 1.4-3.6) were associated significantly with RVFV seropositivity. This study could be important in developing risk-based surveillance for early outbreak detection to limit the spread of RVFV in both human and animal populations.

Detection of Sporadic Outbreaks of Rift Valley Fever in Uganda through the National Viral Hemorrhagic Fever Surveillance System, 2017-2020.

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 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.

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.

Clinical and Molecular Epidemiology of Crimean-Congo Hemorrhagic Fever in Humans in Uganda, 2013-2019.

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.

Sporadic outbreaks of crimean-congo haemorrhagic fever in Uganda, July 2018-January 2019.

INTRODUCTION: Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda's 'cattle corridor', no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks. METHODS: We defined a confirmed case as sudden onset of fever (≥37.5°C) with ≥4 of the following signs and symptoms: anorexia, vomiting, diarrhoea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018-30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4). RESULTS: We identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in western and central region. Of these, eight (73%) case-patients resided in Uganda's 'cattle corridor'. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6-36 years, with persons aged 20-44 years more affected (AR: 7.2/1,000,000) than persons ≤19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock ≤2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (ORM-H = 18, 95% CI = 3.2-∞) and 10 (71%) of 14 case-patients found ticks attached to their bodies ≤2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (ORM-H = 9.3, 95%CI = 1.9-46). CONCLUSIONS: CCHF outbreaks occurred sporadically during 2018-2019, both within and outside 'cattle corridor' districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.

Serological and molecular study of Crimean-Congo Hemorrhagic Fever Virus in cattle from selected districts in Uganda.

BACKGROUND: Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne viral hemorrhagic disease caused by Crimean-Congo Hemorrhagic Fever Virus (CCHFV) that poses serious public health challenges in many parts of Africa, Europe and Asia. METHODS: We examined 500 cattle sera samples from five districts for CCHFV antibodies using in-house and commercially available (IDVet) ELISA, Immunofluorescent assay (IFA) and Real-time polymerase chain reaction (RT-PCR). RESULTS: 500 cattle (73.8 % females) were analyzed; CCHFV seropositivity was 12.6 % (n = 63) and 75.0 % (n = 375) with the in-house and IDVet ELISAs, respectively. Seropositivity was associated with geographical location, increasing age, being female, and having a higher tick burden. Twenty four out of the 37 (64.8 %) were seropositive for CCHFV using IFA and all were negative for virus on RT-PCR. The IFA results were more comparable to IDVet (κcoefficient = 0.88, p = <0.01) than to in-house (κcoefficient = 0.32, p = 0.02). CONCLUSIONS: Our study confirmed the presence and high prevalence of anti-CCHF antibodies in cattle based on three methods from all the five study districts, confirming presence and exposure of CCHFV. Given the zoonotic potential for CCHFV, we recommend a multidisciplinary public health surveillance and epidemiology of CCHFV in both animals and humans throughout the country.

Implementation of the Perinatal Death Surveillance and Response guidelines: Lessons from annual health system strengthening interventions in the Rwenzori Sub-Region, Western Uganda.

Aim: To determine the health facility-based perinatal mortality rate, its causes and avoidable factors using the perinatal mortality surveillance and response guidelines. Design: This was an action study conducted in one of the districts in Western Uganda from 1 January-31 December 2019. Methods: A total of 20 perinatal death cases were recruited consecutively. Data were collected using a Ministry of Health Perinatal Death Surveillance and Response (PDSR) questionnaire containing questions on pregnancy, delivery and immediate postnatal care. We used descriptive statistics to describe key data elements. Results: We found a health facility-based perinatal mortality rate of 17.3 deaths per 1,000 live births. Birth asphyxia was the most common cause of perinatal deaths. Seven, three and ten mothers delayed seeking, reaching and receiving appropriate health care, respectively.

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.

Marburg virus disease outbreak in Kween District Uganda, 2017: Epidemiological and laboratory findings.

INTRODUCTION: In October 2017, a blood sample from a resident of Kween District, Eastern Uganda, tested positive for Marburg virus. Within 24 hour of confirmation, a rapid outbreak response was initiated. Here, we present results of epidemiological and laboratory investigations. METHODS: A district task force was activated consisting of specialised teams to conduct case finding, case management and isolation, contact listing and follow up, sample collection and testing, and community engagement. An ecological investigation was also carried out to identify the potential source of infection. Virus isolation and Next Generation sequencing were performed to identify the strain of Marburg virus. RESULTS: Seventy individuals (34 MVD suspected cases and 36 close contacts of confirmed cases) were epidemiologically investigated, with blood samples tested for MVD. Only four cases met the MVD case definition; one was categorized as a probable case while the other three were confirmed cases. A total of 299 contacts were identified; during follow- up, two were confirmed as MVD. Of the four confirmed and probable MVD cases, three died, yielding a case fatality rate of 75%. All four cases belonged to a single family and 50% (2/4) of the MVD cases were female. All confirmed cases had clinical symptoms of fever, vomiting, abdominal pain and bleeding from body orifices. Viral sequences indicated that the Marburg virus strain responsible for this outbreak was closely related to virus strains previously shown to be circulating in Uganda. CONCLUSION: This outbreak of MVD occurred as a family cluster with no additional transmission outside of the four related cases. Rapid case detection, prompt laboratory testing at the Uganda National VHF Reference Laboratory and presence of pre-trained, well-prepared national and district rapid response teams facilitated the containment and control of this outbreak within one month, preventing nationwide and global transmission of the disease.

First Laboratory-Confirmed Outbreak of Human and Animal Rift Valley Fever Virus in Uganda in 48 Years.

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

Rift valley fever viral load correlates with the human inflammatory response and coagulation pathway abnormalities in humans with hemorrhagic manifestations.

Rift Valley fever virus is an arbovirus that affects both livestock and humans throughout Africa and in the Middle East. Despite its endemicity throughout Africa, it is a rare event to identify an infected individual during the acute phase of the disease and an even rarer event to collect serial blood samples from the affected patient. Severely affected patients can present with hemorrhagic manifestations of disease. In this study we identified three Ugandan men with RVFV disease that was accompanied by hemorrhagic manifestations. Serial blood samples from these men were analyzed for a series of biomarkers specific for various aspects of human pathophysiology including inflammation, endothelial function and coagulopathy. There were significant differences between biomarker levels in controls and cases both early during the illness and after clearance of viremia. Positive correlation of viral load with markers of inflammation (IP-10, CRP, Eotaxin, MCP-2 and Granzyme B), markers of fibrinolysis (tPA and D-dimer), and markers of endothelial function (sICAM-1) were all noted. However, and perhaps most interesting given the fact that these individuals exhibited hemorrhagic manifestations of disease, was the finding of a negative correlation between viral load and P-selectin, ADAMTS13, and fibrinogen all of which are associated with coagulation pathways occurring on the endothelial surface.

Prevalence and risk factors of Rift Valley fever in humans and animals from Kabale district in Southwestern Uganda, 2016.

BACKGROUND: Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV) found in Africa and the Middle East. Outbreaks can cause extensive morbidity and mortality in humans and livestock. Following the diagnosis of two acute human RVF cases in Kabale district, Uganda, we conducted a serosurvey to estimate RVFV seroprevalence in humans and livestock and to identify associated risk factors. METHODS: Humans and animals at abattoirs and villages in Kabale district were sampled. Persons were interviewed about RVFV exposure risk factors. Human blood was tested for anti-RVFV IgM and IgG, and animal blood for anti-RVFV IgG. PRINCIPAL FINDINGS: 655 human and 1051 animal blood samples were collected. Anti-RVFV IgG was detected in 78 (12%) human samples; 3 human samples (0.5%) had detectable IgM only, and 7 (1%) had both IgM and IgG. Of the 10 IgM-positive persons, 2 samples were positive for RVFV by PCR, confirming recent infection. Odds of RVFV seropositivity were greater in participants who were butchers (odds ratio [OR] 5.1; 95% confidence interval [95% CI]: 1.7-15.1) and those who reported handling raw meat (OR 3.4; 95% CI 1.2-9.8). No persons under age 20 were RVFV seropositive. The overall animal seropositivity was 13%, with 27% of cattle, 7% of goats, and 4% of sheep seropositive. In a multivariate logistic regression, cattle species (OR 9.1; 95% CI 4.1-20.5), adult age (OR 3.0; 95% CI 1.6-5.6), and female sex (OR 2.1; 95%CI 1.0-4.3) were significantly associated with animal seropositivity. Individual human seropositivity was significantly associated with animal seropositivity by subcounty after adjusting for sex, age, and occupation (p < 0.05). CONCLUSIONS: Although no RVF cases had been detected in Uganda from 1968 to March 2016, our study suggests that RVFV has been circulating undetected in both humans and animals living in and around Kabale district. RVFV seropositivity in humans was associated with occupation, suggesting that the primary mode of RVFV transmission to humans in Kabale district could be through contact with animal blood or body fluids.