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

Abstract

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.

Prevalence of Crimean-Congo haemorrhagic fever in livestock following a confirmed human case in Lyantonde district, Uganda

“…In Uganda, previous reports have indicated that over 65% of human cases in the country occur among animal handlers [ 25 ]. Evidence of CCHFV prevalence in humans and ticks has been documented in this and other studies [ 26 – 28 ]; however, serosurvey of CCHF in livestock either as part of a viral haemorrhagic fever surveillance program or during outbreaks has not been well described.…”

Ticks; a reservoir for virus emergence at the human-livestock interface in Uganda

“…R. appendiculatus ticks, the most prevalent species, are known to be widespread in Uganda and lack seasonal variation in abundance (17)(18)(19)(20). They are also well-described vectors for zoonotic diseases, as they feed on a wide range of animals as well as humans (21,22), including CCHFV (23,24), Nairobi Sheep Disease Virus (NSDV) (25) and Kadam virus (26,27), all of which are prevalent in Uganda.…”

“…We selected two areas within the cattle corridor (Nakaseke and Lyantonde), classified as high risk districts because of their location in an area of high cattle density and previously-reported human cases of CCHF in the area (Fig 1). We also selected an area (Arua district) outside the cattle corridor (24,29,37,38), classified as a low-risk area where CCHF had never previously been reported, as a control site. The study in Lyantonde coincided with a CCHF outbreak, and ecological sampling of ticks for virome analysis was undertaken as part of an outbreak investigation (39).…”

VSV-based vaccine provides species-specific protection against Sudan virus challenge in macaques

“…We have developed a VSV-based SUDV-specific vaccine candidate expressing the SUDV-Gulu strain GP instead of the VSV glycoprotein (G) (here designated VSV-SUDV). SUDV-Gulu is the causative strain of the biggest recorded SVD outbreak from 2000/01 in Uganda (Table S1) and phylogenetically closer than the original SUDV-Boniface strain to the current outbreak strain 13 . The vaccine vector is based on the VSV G replacement approach and, thus, in principle identical to VSV-EBOV.…”