A chronological review of experimental infection studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus

Abstract

This article provides a definitive review of experimental studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus (CCHFV), the etiologic agent of Crimean-Congo hemorrhagic fever (CCHF), beginning with the first recognized outbreak of the human disease in Crimea in 1944. Published reports by researchers in the former Soviet Union, Bulgaria, South Africa, and other countries where CCHF has been observed show that CCHFV is maintained in nature in a tick-vertebrate-tick enzootic cycle. Human disease most commonly results from the bite of an infected tick, but may also follow crushing of infected ticks or exposure to the blood and tissues of infected animals during slaughter. Wild and domestic animals are susceptible to infection with CCHFV, but do not develop clinical illness. Vertebrates are important in CCHF epidemiology, as they provide blood meals to support tick populations, transport ticks across wide geographic areas, and transmit CCHFV to ticks and humans during the period of viremia. Many aspects of vertebrate involvement in the maintenance and spread of CCHFV are still poorly understood. Experimental investigations in wild animals and livestock provide important data to aid our understanding of CCHFV ecology. This article is the second in a series of reviews of more than 70 years of research on CCHF, summarizing important findings, identifying gaps in knowledge, and suggesting directions for future research.

Keywords: Bunyavirus; Crimean-Congo hemorrhagic fever; Tick-borne; Transmission; Viral hemorrhagic fever.

Figure 1

Life cycle of Hyalomma spp. ticks and vertical and horizontal transmission of Crimean-Congo hemorrhagic fever virus (CCHFV) (3). The course of the tick life cycle is indicated with blue arrows. Upon hatching, larvae find a small animal host for their first blood meal (hematophagy). Depending on the tick species, the larvae either remain attached to their host following engorgement and molt in place (two-host ticks) or drop off to molt (three-host ticks); this transition is marked by an asterisk. The nymphs then either continue to feed on the animal on which they molted (two-host ticks) or attach to a new small vertebrate host (three-host ticks). Upon engorgement, nymphs of all species drop off their host and molt into adults. Adult ticks then find a large animal for hematophagy, and mate while attached to the host. After taking a blood meal, the engorged females drop off and find a suitable location for ovipositing. During the tick life cycle, CCHFV can be transmitted between ticks and mammals (solid red arrows), and directly between ticks through co-feeding (dashed arrows). For each kind of virus transfer, the thickness of the arrow indicates the efficiency of transmission. Humans can become infected through the bite of an infected tick or through exposure to the body fluids of a viremic animal or an infected person.

Figure 2

Idealized life cycle of an Ixodes spp. tick with three hosts, showing the three stages (larva, nymph, and adult) (16). The eggs incubate in ground litter (A), protected against stressful environmental conditions (e.g., water losses). When the larvae hatch, they climb the vegetation, questing for a host (A→B). Larvae feed on such hosts (B), and when engorged, drop off to the ground and molt to nymphs (B→C). The nymphs quest for a second host, feed, and molt again off the host (C→D). The resulting adults attach to a third host, feed, and mate, and the females drop off for ovipositing on the ground.