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Mpox was first identified against the backdrop of the smallpox eradication campaign. Monkeypox virus (MPXV), the causative agent of mpox, has been maintained in animal reservoirs in the forested regions of West and Central Africa as 2 distinct clades; clade I has historically caused more severe infection in Central Africa than clade II, historically found in West Africa. However, rapid reemergence and spread of both MPXV clades through novel routes of transmission have challenged the known characteristics of mpox. We summarize mpox demographic distribution, clinical severity, and case-fatality rates attributed to genetically distinct MPXV subclades and focus on MPXV clade Ib, the more recently identified subclade. Broad worldwide assistance will be necessary to halt the spread of both MPXV clades within mpox endemic and nonendemic regions to prevent future outbreaks.

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. 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). 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). 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.

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.

In Africa, Rift Valley Fever poses a substantial risk to animal health, and human cases occur after contact with infected animals or their tissues. RVF has re-emerged in Uganda after nearly five decades, with multiple outbreaks recorded since 2016. We investigated a unique RVF outbreak associated with an animal abortion storm of 30 events and human cases on a dairy farm in Mbarara District, Western Uganda, in February 2023. Genomic analysis was performed, comparing animal and human RVF viruses (RVFV) circulating in the region. A cluster of thirteen human RVF cases and nine PCR-positive animals could directly be linked with the abortion storm. Overall, during the year 2023, we confirmed 61 human RVFV cases across Uganda, 88.5% of which were reported to have had direct contact with livestock, and a high case fatality rate of 31%. We recommend implementing extensive health education programs in affected communities and using sustainable mosquito control strategies to limit transmission in livestock, coupled with initiating animal vaccination trials in Uganda.

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. 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. 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). 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.

Introduction Due to the difficulty in attributing a causative agent to acute febrile illnesses (AFI), multi-pathogen diagnostic tools should be prioritized in low-resource settings. A previously developed AFI-TaqMan Array Card (AFI-TAC), capable of detecting 26 pathogens within 2 h of nucleic acid extraction, was evaluated in Uganda. Methods A cross-sectional retrospective study design was employed and utilized 182 viral hemorrhagic fever (VHF)-negative samples collected from Uganda, DRC, South Sudan and Kenya during routine surveillance from August 2018- March, 2019. These samples were tested on AFI-TAC targeting 17 viral, 8 bacterial and 3 protozoal pathogens known to cause fever. Patients with a body temperature of ≥ 38 °C, were bleeding, and had any other febrile symptoms were included. Previously confirmed VHF positive samples were used for assay verification. Results Overall, 7 pathogens were detected in 59 samples (32.42%) as follows: Plasmodium spp. ( n  = 49, 26.92%), non-typhoidal Salmonella ( n  = 3, 1.65%), Yellow Fever (YF) virus ( n  = 2, 1.10%), Salmonella enterica serovar typhi ( n  = 2, 1.10%), Leptospira spp ( n  = 1, 0.55%), Streptococcus pneumoniae ( n  = 1, 0.55%) and Rickettsia spp. ( n  = 1, 0.55%). Final outcome (alive vs. dead) as abstracted from case report forms differed significantly by pathogen category ( p  = 0.002) was significantly associated with assay positivity. We compared outcome across pathogen categories using a chi-square/Fisher’s exact test, as appropriate, reporting p-values (Table 2). Cough was the only clinical symptom significantly associated with Plasmodium infection ( p  = 0.016). Conclusion The TAC is a feasible, readily adoptable diagnostic tool for use in Uganda and other sub-Saharan countries, particularly when incorporated into the national testing algorithm for differential diagnosis during AFI outbreaks and surveillance. Clinical trial number Not applicable.

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.

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 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.

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.