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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.

Uganda reported cases of Rift Valley fever virus (RVFV) for the first time in almost 50 years in 2016, following an outbreak of Rift Valley fever (RVF) that caused four human infections, two of which resulted in death. Subsequent outbreak investigation serosurveys found high seroprevalence of IgG antibodies without evidence of acute infection or IgM antibodies, suggesting the possibility of undetected RVFV circulation prior to the outbreak. After the 2016 outbreak investigation, a serosurvey was conducted in 2017 among domesticated livestock herds across Uganda. Sampling data were incorporated into a geostatistical model to estimate RVF seroprevalence among cattle, sheep, and goats. Variables resulting in the best fit to RVF seroprevalence sampling data included annual variability in monthly precipitation and enhanced vegetation index, topographic wetness index, log human population density percent increase, and livestock species. Individual species RVF seroprevalence prediction maps were created for cattle, sheep, and goats, and a composite livestock prediction was created based on the estimated density of each species across the country. Seroprevalence was greater in cattle compared with sheep and goats. Predicted seroprevalence was greatest in the central and northwestern quadrant of the country, surrounding Lake Victoria, and along the Southern Cattle Corridor. We identified areas that experienced conditions conducive to potential increased RVFV circulation in 2021 in central Uganda. An improved understanding of the determinants of RVFV circulation and locations with high probability of elevated RVF seroprevalence can guide prioritization of disease surveillance and risk mitigation efforts.

BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase–polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.)

Crimean-Congo hemorrhagic fever (CCHF) is a highly fatal zoonotic disease endemic to Kazakhstan. Previous work estimated the seroprevalence of CCHF virus (CCHFV) among livestock owners in the Zhambyl region of southern Kazakhstan at 1.2%. To estimate CCHFV seroprevalence among cattle and sheep, we selected 15 villages with known history of CCHFV circulation (endemic) and 15 villages without known circulation (nonendemic) by cluster sampling with probability proportional to livestock population size. We collected whole blood samples from 521 sheep and 454 cattle from randomly selected households within each village and collected ticks found on the animals. We tested livestock blood for CCHFV-specific IgG antibodies by ELISA; ticks were screened for CCHFV RNA by real-time reverse transcription polymerase chain reaction and CCHFV antigen by antigen-capture ELISA. We administered questionnaires covering animal demographics and livestock herd characteristics to an adult in each selected household. Overall weighted seroprevalence was 5.7% (95% CI: 3.1, 10.3) among sheep and 22.5% (95% CI: 15.8, 31.2) among cattle. CCHFV-positive tick pools were found on two sheep (2.4%, 95% CI: 0.6, 9.5) and three cattle (3.8%, 95% CI: 1.2, 11.5); three CCHFV-positive tick pools were found in nonendemic villages. Endemic villages reported higher seroprevalence among sheep (15.5% versus 2.8%, P < 0.001) but not cattle (25.9% versus 20.1%, P = 0.42). Findings suggest that the current village classification scheme may not reflect the geographic distribution of CCHFV in Zhambyl and underscore that public health measures must address the risk of CCHF even in areas without a known history of circulation.

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.

Uganda is highly vulnerable to public health emergencies (PHEs) due to its geographic location next to the Congo Basin epidemic hot spot, placement within multiple epidemic belts, high population growth rates, and refugee influx. In view of this, Uganda's Ministry of Health established the Public Health Emergency Operations Center (PHEOC) in September 2013, as a central coordination unit for all PHEs in the country. Uganda followed the World Health Organization's framework to establish the PHEOC, including establishing a steering committee, acquiring legal authority, developing emergency response plans, and developing a concept of operations. The same framework governs the PHEOC's daily activities. Between January 2014 and December 2021, Uganda's PHEOC coordinated response to 271 PHEs, hosted 207 emergency coordination meetings, trained all core staff in public health emergency management principles, participated in 21 simulation exercises, coordinated Uganda's Global Health Security Agenda activities, established 6 subnational PHEOCs, and strengthened the capacity of 7 countries in public health emergency management. In this article, we discuss the following lessons learned: PHEOCs are key in PHE coordination and thus mitigate the associated adverse impacts; although the functions of a PHEOC may be legalized by the existence of a National Institute of Public Health, their establishment may precede formally securing the legal framework; staff may learn public health emergency management principles on the job; involvement of leaders and health partners is crucial to the success of a public health emergency management program; subnational PHEOCs are resourceful in mounting regional responses to PHEs; and service on the PHE Strategic Committee may be voluntary.

On August 1, 2018, the Democratic Republic of the Congo (DRC) declared its 10th Ebola virus disease (Ebola) outbreak in an area with a high volume of cross-border population movement to and from neighboring countries. The World Health Organization (WHO) designated Rwanda, South Sudan, and Uganda as the highest priority countries for Ebola preparedness because of the high risk for cross-border spread from DRC (1). Countries might base their disease case definitions on global standards; however, historical context and perceived risk often affect why countries modify and adapt definitions over time, moving toward or away from regional harmonization. Discordance in case definitions among countries might reduce the effectiveness of cross-border initiatives during outbreaks with high risk for regional spread. CDC worked with the ministries of health (MOHs) in DRC, Rwanda, South Sudan, and Uganda to collect MOH-approved Ebola case definitions used during the first 6 months of the outbreak to assess concordance (i.e., commonality in category case definitions) among countries. Changes in MOH-approved Ebola case definitions were analyzed, referencing the WHO standard case definition, and concordance among the four countries for Ebola case categories (i.e., community alert, suspected, probable, confirmed, and case contact) was assessed at three dates (2). The number of country-level revisions ranged from two to four, with all countries revising Ebola definitions by February 2019 after a December 2018 peak in incidence in DRC. Case definition complexity increased over time; all countries included more criteria per category than the WHO standard definition did, except for the "case contact" and "confirmed" categories. Low case definition concordance and lack of awareness of regional differences by national-level health officials could reduce effectiveness of cross-border communication and collaboration. Working toward regional harmonization or considering systematic approaches to addressing country-level differences might increase efficiency in cross-border information sharing.

Crimean-Congo hemorrhagic fever (CCHF), Q fever, and Lyme disease are endemic to southern Kazakhstan, but population-based serosurveys are lacking. We assessed risk factors and seroprevalence of these zoonoses and conducted surveys for CCHF-related knowledge, attitudes, and practices in the Zhambyl region of Kazakhstan. Weighted seroprevalence for CCHF among all participants was 1.2%, increasing to 3.4% in villages with a known history of CCHF circulation. Weighted seroprevalence was 2.4% for Lyme disease and 1.3% for Q fever. We found evidence of CCHF virus circulation in areas not known to harbor the virus. We noted that activities that put persons at high risk for zoonotic or tickborne disease also were risk factors for seropositivity. However, recognition of the role of livestock in disease transmission and use of personal protective equipment when performing high-risk activities were low among participants.

On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff members at biosafety level 4 facilities in the United States (1).

Rift Valley fever (RVF) is caused by RVF virus (RVFV), a single-stranded RNA virus in the Bunyavirales order, Phenuiviridae family, and Phlebovirus genus. It is an emerging epidemic disease of humans and livestock and an important endemic problem in sub-Saharan Africa.1 Rift Valley fever virus is transmitted to livestock and humans by the bite of infected mosquitoes or exposure to tissues or blood of infected animals.2 Interepidemic virus maintenance is thought to occur either transovarially in Aedes species mosquitoes or through cycling of low-level transmission between domestic livestock or wild ungulates and mosquitoes.3 After periods of heavy rainfall, Aedes mosquitoes rapidly emerge, resulting in extensive amplification of the virus through infection of livestock.2 Presentation of RVF in animals can vary among species with a range of clinical severity. Livestock, particularly cattle, sheep, and goats are highly susceptible to RVFV and present with symptoms of fever, loss of appetite, weakness, low milk production, nasal discharge, vomiting, and diarrhea. During large epizootics, “abortion storms,” particularly in sheep and cattle, have been identified. High newborn mortality (80–100%) and adult mortality (5–20%) may also be observed.3 Humans infected with RVFV typically have mild, self-limited febrile illness, but can present in a small number of cases (< 8%) with severe jaundice, rhinitis, encephalitis, and hemorrhagic manifestations. Retinal degeneration (5–10% of cases), hemorrhagic fever (< 1%), or encephalitis (< 1%) may also develop.4,5 Outbreaks of RVF have been reported most frequently in East Africa, especially Kenya, Somalia, and Tanzania, with the last major outbreak in the region recorded in 1997–1998. However, outbreaks have also been reported in other African countries, including Egypt, South Africa, Madagascar, and Senegal.6 In 2000, the first RVF outbreak outside of Africa was reported in Saudi Arabia and Yemen.5,7 More recently, Kenya and Tanzania experienced a large epizootic of RVFV in 2006–2007 and Sudan in 2010.6 The emergence of RVFV in East Africa resulted in widespread livestock morbidity and mortality, with hundreds of laboratory-confirmed human cases, and likely thousands of asymptomatic or mild RVFV human infections going undetected.8,9 Rift Valley fever virus in Uganda was first detected in mosquitos collected in Semliki forest, Western Uganda, in 1944,10 and has since been detected several times by the East African Virus Research Institute (EAVRI), now the Uganda Virus Research Institute (UVRI). Human cases were recorded during outbreaks occurring near Entebbe in 1960 and 1962.11,12 Since then, serological evidence of human and livestock RVFV infections in Uganda have been intermittently reported,13,14 but the last published description of acute human RVFV infection was seven cases occurring near Entebbe in 1968.15 On March 10, 2016, UVRI and the Uganda Ministry of Health (MOH) received a report of a suspected viral hemorrhagic fever (VHF) case presenting to Kabale Regional Referral Hospital (KRRH) in Kabale district in southwestern Uganda. The initial case was of a 48-year-old male butcher who had been working in a local abattoir, where livestock were brought for slaughter. The patient presented with a history of fever, vomiting, diarrhea, headache, and hemorrhagic symptoms (bleeding gums, epistaxis, bloody urine, and stools). A blood sample was taken and sent to the UVRI VHF laboratory for testing. On March 11, a second suspected VHF case presented to KRRH with similar symptoms; a blood sample was collected for testing. This patient was a 16-year-old male student first reported by Kabale District Health Office from the Uganda–Rwanda border village of Katuna. Both samples were tested for hemorrhagic fever viruses, including Ebola viruses, Marburg virus, Crimean–Congo hemorrhagic fever virus, and RVFV. Both specimens were found to be positive for RVFV by reverse transcriptase polymerase chain reaction (RT-PCR) and IgM serology.

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.

Background Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda’s experience in EVD preparedness. Results On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. Conclusion As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a “fire-fighting” approach during public health emergencies.

BackgroundDuring 2017, a multistate outbreak investigation occurred after the confirmation of Seoul virus (SEOV) infections in people and pet rats. A total of 147 humans and 897 rats were tested.MethodsIn addition to immunoglobulin (Ig)G and IgM serology and traditional reverse-transcription polymerase chain reaction (RT-PCR), novel quantitative RT-PCR primers/probe were developed, and whole genome sequencing was performed.ResultsSeventeen people had SEOV IgM, indicating recent infection; 7 reported symptoms and 3 were hospitalized. All patients recovered. Thirty-one facilities in 11 US states had SEOV infection, and among those with ≥10 rats tested, rat IgG prevalence ranged 2%–70% and SEOV RT-PCR positivity ranged 0%–70%. Human laboratory-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (P = .03 and P = .006, respectively). Genomic sequencing identified >99.5% homology between SEOV sequences in this outbreak, and these were >99% identical to SEOV associated with previous pet rat infections in England, the Netherlands, and France. Frequent trade of rats between home-based ratteries contributed to transmission of SEOV between facilities.ConclusionsPet rat owners, breeders, and the healthcare and public health community should be aware and take steps to prevent SEOV transmission in pet rats and to humans. Biosecurity measures and diagnostic testing can prevent further infections.

Background: Crimean–Congo hemorrhagic fever (CCHF) is the most geographically widespread tick-borne viral infection. Outbreaks of CCHF in sub-Saharan Africa are largely undetected and thus under-reported. On November 9, 2015, the National Viral Hemorrhagic Fever Laboratory at the Uganda Virus Research Institute received an alert for a suspect VHF case in a 33-year-old male who presented with VHF compatible signs and symptoms at Mengo Hospital in Kampala. Methods: A blood sample from the suspect patient was tested by RT-PCR for CCHF and found positive. Serological testing on sequential blood specimens collected from this patient showed increasing anti-CCHFV IgM antibody titers, confirming recent infection. Repeat sampling of the confirmed case post recovery showed high titers for anti-CCHFV-specific IgG. An epidemiological outbreak investigation was initiated following the initial RT-PCR positive detection to identify any additional suspect cases. Results: Only a single acute case of CCHF was detected from this outbreak. No additional acute CCHF cases were identified following field investigations. Environmental investigations collected 53 tick samples, with only 1, a Boophilus decoloratus, having detectable CCHFV RNA by RT-PCR. Full-length genomic sequencing on a viral isolate from the index human case showed the virus to be related to the DRC (Africa 2) lineage. Conclusions: This is the fourth confirmed CCHF outbreak in Uganda within 2 years after more than 50 years of no reported human CCHF cases in this country. Our investigations reaffirm the endemicity of CCHFV in Uganda, and show that exposure to ticks poses a significant risk for human infection. These findings also reflect the importance of having an established national VHF surveillance system and diagnostic capacity in a developing country like Uganda, in order to identify the first cases of VHF outbreaks and rapidly respond to reduce secondary cases. Additional efforts should focus on implementing effective tick control methods and investigating the circulation of CCHFV throughout the country. Keywords: Crimean–Congo hemorrhagic fever, Uganda, Outbreak, CCHF

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.

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., Author summary Marburg virus disease (MVD) is caused by the virus that belongs to the same family as that of Ebola Virus disease. The disease is characterized by severe clinical symptoms such as high fever, diarrhoea and vomiting, and severe bleeding from most body openings. On average, 54% of the people who get infected with Marburg virus die from it [1]. In October 2017, Uganda reported an outbreak of MVD in the eastern district of Kween that borders Kenya in the Mount Elgon plains. This was the first time MVD was being detected in this part of the country since previous MVD outbreaks had been reported in the western part of Uganda. The Ministry of Health together with partners instituted rapid outbreak response for control. Investigations revealed a cluster of one family involving four cases whereby only one survived. The outbreak was traced back into bat caves in Kween district. Rock salt mining in the cave led to a spill-over of the virus into the human population with the subsequent person-to-person transmission. Through contact tracing and isolation of the infected people among other approaches, the outbreak was brought under control as explained in this article.

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., Author summary Viral hemorrhagic fevers are known to cause high morbidity and mortality and pose a serious threat to human and animal populations in endemic countries. An outbreak of Rift Valley fever was detected in Kabale district in March, 2016 and identified the first human cases in Uganda since 1968. There was a need to perform a rapid assessment of the burden of Rift valley fever in Kabale district, identify undetected acute cases, identify risk factors associated with human disease, identify areas at high-risk or future infections, and to determine if this was a newly emerging infection or an endemic disease. Our study found the seroprevalence to be as high as 28% in humans and 36% in animals within some subcounties of Kabale district. Human seropositivity correlated with animal seropositivity, suggesting that animal to human transmission may be the predominant mode of virus spread. Our findings also suggest that this virus may have been endemic for many years prior to these human cases being identified.

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.

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., Author summary Rift Valley fever virus is an emerging virus of public health significance. In endemic areas up to 60% of the population are seropositive by adulthood. This implies that most of the individuals living in these endemic areas become infected with this virus at some point in their lifetime. This highly prevalent virus is poorly understood likely secondary to lack of diagnostic capacity in affected areas. In fact, the majority of cases are undocumented and spontaneously resolve. However, in some individuals the disease can be very severe and at times associated with hemorrhage or encephalitis. In this report we identify three men infected during the acute stage who also exhibited hemorrhagic manifestations. These men had elevated cytokine and chemokine levels consistent with immune activation. Our data show that biomarkers of fibrinolysis correlated positively with virus while biomarkers of coagulation correlated negatively with virus, suggesting that opposing hemostatic pathways are altered during disease, and that they correct with resolution of viremia.

Background Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples’ knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages. Methods The study was a community survey done in Luweero, Ibanda and Kamwenge districts that have experienced outbreaks of Ebola and Marburg virus diseases. Quantitative data were collected using a structured questionnaire and triangulated with qualitative participatory epidemiology techniques to gain a communities’ knowledge and attitude towards Ebola and Marburg virus disease. Results Out of 740 respondents, 48.5% (359/740) were categorized as being knowledgeable about Ebola and Marburg virus diseases, whereas 60.5% (448/740) were having a positive attitude towards control and prevention of Ebola and Marburg virus diseases. The mean knowledge and attitude percentage scores were 54.3 (SD = 23.5, 95%CI = 52.6–56.0) and 69.9 (SD = 16.9, 95%CI = 68.9–71.1) respectively. People educated beyond primary school were more likely to be knowledgeable about Ebola and Marburg virus disease than those who did not attain any formal education (OR = 3.6, 95%CI = 2.1–6.1). Qualitative data revealed that communities describe Ebola and Marburg virus diseases as very severe diseases with no cure and they believe the diseases spread so fast. Respondents reported fear and stigma suffered by survivors, their families and the broader community due to these diseases. Conclusion Communities in Uganda affected by filovirus outbreaks have moderate knowledge about these diseases and have a positive attitude towards practices to prevent and control Ebola and Marburg viral diseases. The public health sector should enhance this community knowledge gap to empower them more by supplying educational materials for epidemic preparedness in future using appropriate communication channels as proposed by the communities., Author summary Ebola Virus Disease (EVD) and Marburg Virus Disease (MVD) are caused by a family of viruses known as Filoviruses. When they occur, they cause high lethality among infected people, which causes panic to the population, as well as interfering with the health care delivery system, especially in developing countries. Usually, at the beginning of these infections, the affected communities tend to think that witchcraft or some bad luck has befallen their community. Because of limited knowledge about these diseases, it becomes hard for local authorities to institute control and prevention measures. We administered a questionnaire to individual participants and held focus group discussions to help us tease out the communities’ understanding of these diseases. We found that people have moderate knowledge about EVD and MVD, and a positive attitude towards the prevention and control measures instituted by health authorities in Uganda. However, they still reported stigma subjected to the survivors of these diseases and affected families at large. EVD still causes much fear which drives some of the irrational actions by communities during outbreaks. Communities highlighted early sensitization as a means of controlling outbreaks. We recommend the findings in this paper to public health authorities in epidemic-prone countries like Uganda to aid in control and epidemic preparedness of filovirus outbreaks.

To the Editor: Marburg virus (MARV) and Ravn virus (RAVV), collectively called marburgviruses, cause Marburg hemorrhagic fever (MHF) in humans. In July 2007, 4 cases of MHF (1 fatal) occurred in miners at Kitaka Mine in southern Uganda. Later, MHF occurred in 2 tourists who visited Python Cave, ≈50 km from Kitaka Mine. One of the tourists was from the United States (December 2007) and 1 was from the Netherlands (July 2008); 1 case was fatal (1,2,3). The cave and the mine each contained 40,000–100,000 Rousettus aegyptiacus bats (Egyptian fruit bats). Longitudinal investigations of the outbreaks at both locations were initiated by the Viral Special Pathogens Branch of the Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA, and Entebbe, Uganda) in collaboration with the Uganda Wildlife Authority (UWA) and the Uganda Virus Research Institute (UVRI). During these studies, genetically diverse MARVs and RAVVs were isolated directly from bat tissues, and infection levels of the 2 viruses were found to increase in juvenile bats on a predictable bi-annual basis (4,5). However, investigations at Kitaka Mine were stopped when the miners exterminated the bat colony by restricting egress from the cave with papyrus reed barriers and then entangling the bats in fishing nets draped over the exits. The trapping continued for weeks, and the entrances were then sealed with sticks and plastic. These depopulation efforts were documented by researchers from UVRI, the CDC, the National Institute of Communicable Diseases (Sandringham, South Africa), and UWA during site visits to Kitaka Mine (Technical Appendix Figure). In August 2008, thousands of dead bats were found piled in the forest, and by November 2008, there was no evidence of bats living in the mine; whether 100% extermination was achieved is unknown. CDC, UVRI, and UWA recommended against extermination, believing that any results would be temporary and that such efforts could exacerbate the problem if bat exclusion methods were not complete and permanent (6,7). In October 2012, the most recent known marburgvirus outbreak was detected in Ibanda, a town in southwest Uganda. Ibanda is ≈20 km from the Kitaka Mine and is the urban center that serves smaller communities in the Kitaka area. This MHF outbreak was the largest in Ugandan history: 15 laboratory-confirmed cases occurred (8). In November 2012, an ecologic investigation of the greater Ibanda/Kitaka area was initiated. The investigation included interviews with local authorities to locate all known R. aegyptiacus colonies in the area. Although minor colonies of small insectivorous bats were found, the only identifiable colony of R. aegyptiacus bats was found inside the re-opened Kitaka Mine, albeit at much reduced size, perhaps 1%–5% of that found before depopulation efforts. To determine whether the R. aegyptiacus bats that had repopulated Kitaka Mine were actively infected with marburgviruses, we tested 400 bats by using previously described methods (4,5). Viral RNA was extracted from ≈100 mg of liver and spleen tissue by using the MagMAX Total Nucleic Acid Isolation Kit (Applied Biosystems, Foster City, CA, USA) according to the manufacturer’s recommended protocol. The Fisher exact test was conducted by using IBM SPSS Statistics, version 19.0 (IBM Corp., Armonk, NY, USA). Of the 400 R. aegyptiacus bats collected, 53 (13.3%) were positive for marburgvirus RNA by quantitative reverse transcription PCR (32/233 [13.7%] adults and 21/167 [12.6%] juveniles; Technical Appendix Table); marburgvirus was isolated from tissue samples from 9 of the 400 bats. The overall level of active infection was significantly higher than that found in Kitaka Mine during 2007–2008 (5.1%) (5) (Fisher exact test, p 0.5 for both), and overall, the presence of virus-specific IgG among the bats was 16.5%, a finding consistent with that in previous studies (4,5). Figure Phylogeny of concatenated marburgvirus nucleoprotein (NP) and viral protein 35 (VP35) gene fragments as determined by using the maximum-likelihood method. Sequences from the NP (289–372 nt) and VP35 (203–213 nt) genes were amplified and ... Phylogenetic analysis of viral RNA genome fragment sequences in this study showed high marburgvirus genetic diversity, including the presence of RAVVs and MARVs. Sequences for isolates from 3 bats were nearly identical to those of the MARV isolates obtained from patients in the 2012 Ibanda outbreak (8), suggesting that bats from Kitaka Mine were a likely source of the virus. Technical Appendix: Photographs taken during August 2008–September 2009 of bat extermination efforts at Kitaka Mine, and table showing demographic characteristics of bats captured during a Marburg hemorrhagic fever outbreak investigation at the mine in November 2012, Uganda. Click here to view.(124K, pdf)

Background In January 2018, a patient admitted to a Delaware hospital tested positive for New World hantavirus by IgM and IgG ELISA. Subsequent testing by CDC’s Viral Special Pathogens Branch (VSPB) confirmed Andes virus (ANDV) by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. ANDV is transmitted to humans through contact with long-tailed rice rats endemic to Argentina and Chile. Unlike other hantavirus species, ANDV can be transmitted person to person, but transmission is typically limited to close contacts of ill persons. Because of this risk, a contact tracing investigation was initiated by CDC, state and county health departments. Method A suspect case was defined as a person with close contact with the traveler who became ill within the maximum incubation period (42 days) following last contact. A high-risk contact was defined as a person with exposure to the traveler’s body fluids. A low-risk contact was defined as a person who had provided care or in-flight service to, or was seated near the traveler for at least 1 hour, in the absence of exposure to body fluids. All contacts were advised to self-monitor their temperature daily for 42 days from last contact, and to seek medical care for any of the specified symptoms. Contacts that developed symptoms were tested for ANDV by RT-PCR and serology by VSPB. Result Fifty-three contacts were identified in six states; 51 were successfully reached. Of these, 28 were healthcare workers, 15 were airline contacts, seven were acquaintances of the traveler, and one was a hospital roommate. Two high-risk contacts were identified, both of whom remained asymptomatic. Six low-risk contacts reported influenza-like illness, diarrhea, or mild rhinitis during the incubation period. All six symptomatic low-risk contacts tested negative for ANDV by PCR, IgM, and IgG. The remaining low-risk contacts remained asymptomatic. Conclusion Hospitalized patients with ANDV should be managed with standard, contact, and droplet precautions. While the risk of human-to-human transmission is low, contact tracing should be considered to identify potential cases and limit additional exposures. Health providers should consider ANDV in returning travelers with a nonspecific febrile or acute respiratory illness who have traveled to the Andes region of Argentina or Chile in the preceding 6 weeks. Disclosures All authors: No reported disclosures.

In 2012, an unprecedented number of four distinct, partially overlapping filovirus-associated viral hemorrhagic fever outbreaks were detected in equatorial Africa. Analysis of complete virus genome sequences confirmed the reemergence of Sudan virus and Marburg virus in Uganda, and the first emergence of Bundibugyo virus in the Democratic Republic of the Congo.

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.

Background Rift Valley Fever virus (RVF) is a zoonotic virus in the Phenuiviridae family. RVF outbreaks can cause significant morbidity and mortality in humans and animals. Following the diagnosis of two RVF cases in March 2016 in southern Kabale district, Uganda, we conducted a knowledge, attitudes and practice (KAP) survey to identify knowledge gaps and at-risk behaviors related to RVF. Methodology/Principal findings A multidisciplinary team interviewed 657 community members, including abattoir workers, in and around Kabale District, Uganda. Most participants (90%) had knowledge of RVF and most (77%) cited radio as their primary information source. Greater proportions of farmers (68%), herdsmen (79%) and butchers (88%) thought they were at risk of contracting RVF compared to persons in other occupations (60%, p, Author summary Rift Valley Fever (RVF) virus is transmitted to humans from contact with infected livestock and through mosquito bites. Several human cases of RVF were diagnosed in Kabale District, Uganda in March 2016, over 40 years after the last RVF case was identified in Uganda. We administered a knowledge, attitudes, and practice survey to people living in Kabale District, near where the cases occurred. Survey results demonstrated that knowledge, attitudes and practice surrounding RVF could be improved within the community.

Rift Valley fever (RVF) virus is a mosquito-borne virus associated with large-scale epizootics/epidemics throughout Africa and the Arabian peninsula. Virus infection can result in economically disastrous “abortion storms” and high newborn mortality in livestock. Human infections result in a flu-like illness, with 1 to 2% of patients developing severe complications, including encephalitis or hemorrhagic fever with high fatality rates. There is a critical need for a highly sensitive and specific molecular diagnostic assay capable of detecting the natural genetic spectrum of RVF viruses. We report here the establishment of a pan-RVF virus quantitative real-time reverse transcription-PCR assay with high analytical sensitivity (∼5 RNA copies of in vitro-transcribed RNA/reaction or ∼0.1 PFU of infectious virus/reaction) and efficiency (standard curve slope = −3.66). Based on the alignments of the complete genome sequences of 40 ecologically and biologically diverse virus isolates collected over 56 years (1944 to 2000), the primer and probe annealing sites targeted in this assay are known to be located in highly conserved genomic regions. The performance of this assay relative to serologic assays is illustrated by testing of known RVF case materials obtained during the Saudi Arabia outbreak in 2000. Furthermore, analysis of acute-phase blood samples collected from human patients (25 nonfatal, 8 fatal) during that outbreak revealed that patient viremia at time of presentation at hospital may be a useful prognostic tool in determining patient outcome.

Thermodynamic modeling of Ebola viral RNA predicts the formation of RNA stem-loop structures at the 3′ and 5′ termini and panhandle structures between the termini of the genomic (or antigenomic) RNAs. Sequence analysis showed a high degree of identity among Ebola Zaire, Sudan, Reston, and Cote d’Ivoire subtype viruses in their 3′ and 5′ termini (18 nucleotides in length) and within a second region (internal by approximately 20 nucleotides). While base pairing of the two conserved regions could lead to the formation of the base of the putative stem-loop or panhandle structures, the intervening sequence variation altered the predictions for the rest of the structures. Using an in vivo minigenome replication system, we engineered mutations designed to disrupt potential base pairing in the viral RNA termini. Analysis of these variants by screening for enhanced green fluorescent protein reporter expression and by quantitation of minigenomic RNA levels demonstrated that the upper portions of the putative panhandle and 3′ genomic structures can be destabilized without affecting virus replication.

Outbreaks of Ebola and Marburg virus diseases have recently increased in frequency in Uganda. This increase is probably caused by a combination of improved surveillance and laboratory capacity, increased contact between humans and the natural reservoir of the viruses, and fluctuations in viral load and prevalence within this reservoir. The roles of these proposed explanations must be investigated in order to guide appropriate responses to the changing epidemiological profile. Other African settings in which multiple filoviral outbreaks have occurred could also benefit from such information.

Increasingly, the need to strengthen global capacity to prevent, detect, and respond to public health threats around the globe is being recognized. CDC, in partnership with the World Health Organization (WHO), has committed to building capacity by assisting member states with strengthening their national capacity for integrated disease surveillance and response as required by International Health Regulations (IHR). CDC and other U.S. agencies have reinforced their pledge through creation of global health security (GHS) demonstration projects. One such project was conducted during March-September 2013, when the Uganda Ministry of Health (MoH) and CDC implemented upgrades in three areas: 1) strengthening the public health laboratory system by increasing the capacity of diagnostic and specimen referral networks, 2) enhancing the existing communications and information systems for outbreak response, and 3) developing a public health emergency operations center (EOC) (Figure 1). The GHS demonstration project outcomes included development of an outbreak response module that allowed reporting of suspected cases of illness caused by priority pathogens via short messaging service (SMS; i.e., text messaging) to the Uganda District Health Information System (DHIS-2) and expansion of the biologic specimen transport and laboratory reporting system supported by the President's Emergency Plan for AIDS Relief (PEPFAR). Other enhancements included strengthening laboratory management, establishing and equipping the EOC, and evaluating these enhancements during an outbreak exercise. In 6 months, the project demonstrated that targeted enhancements resulted in substantial improvements to the ability of Uganda's public health system to detect and respond to health threats.