Crimean-Congo hemorrhagic fever

Causative agent and history of study

The causative agent of the infection belongs to the family Bunyaviridae and is classified in the genus Nairovirus (CCHF antigenic group). It is a vasotropic arbovirus which, unlike many other arboviruses, lacks hemagglutinating activity in most strains. Eight different genotypes of the pathogen have been identified worldwide, each with a strict geographic restriction.

The disease was first described in 1944 by military physicians in Crimea. The infection massively affected soldiers and settlers during agricultural work (haymaking). As early as 1945, researcher M.P. Chumakov successfully isolated the virus both from the blood of patients and from ixodid ticks. Two decades later, in 1966, an agent was isolated in Congo that, upon thorough examination, proved to be biologically identical to the Crimean virus. This discovery gave the infection its current double name.

Epidemiology and ecology of the virus

In the territory of the Russian Federation, natural foci of the infection are traditionally registered in the southern regions. The reservoir and source of the pathogen are pasture ticks, primarily representatives of the genus Hyalomma, which are capable of retaining the viral particle for up to 250 days. In nature, the virus survives the interepidemic period through unique mechanisms of transmission within the arthropod population:

• Transovarial transmission: the virus is transmitted from an infected female directly to her offspring.
• Transstadial transmission: the pathogen persists in the organism through its metamorphosis (from larva to nymph and adult).

Vertebrate animals also play a significant role in maintaining natural foci. Larvae and nymphs feed on ground-nesting birds, hares, and mouse-like rodents. Adult ticks prefer large and small ruminants (cows, sheep) and camels. Infected animals develop viremia lasting up to 10 days—sufficient time to successfully infect new batches of ticks, while the disease itself in animals is predominantly asymptomatic.

Humans in this epidemiological chain represent a "biological dead end." The main route of transmission in natural foci remains transmissive (bite of an infected tick). However, the contact route of transmission is extremely dangerous; it is realized through skin microtraumas and mucous membranes upon contact with the blood of patients, crushing ticks, or during medical procedures (artificial nosocomial route). The aerogenic mechanism, characteristic of laboratory accidents, is less common. Contact transmission has a critical feature—the "ping-pong" effect: upon passage through the human body, the virus sharply increases its virulence, causing such cases to be significantly more severe.

Pathogenesis and clinical presentation

The disease can occur in two forms: with hemorrhagic manifestations and without them (the latter is tolerated much more easily by patients). In the classic hemorrhagic form, the incubation period ranges from 1 to 14 days.

Pathogenesis develops in stages:

1. Primary replication: the virus actively multiplies in the cells of the macrophage system.
2. Hematogenous dissemination: massive release of the pathogen into the bloodstream.
3. Vascular damage: due to the strict vasotropism of the virus, severe generalized capillariotoxicosis develops.

In the clinical blood test against the background of the classic triad (fever, intoxication, hemorrhagic syndrome), thrombocytopenia and leukopenia are clearly traceable. Mortality in the development of the hemorrhagic form reaches 16–20%, and up to 50% in contact transmission. The main causes of patient death are infectious-toxic shock (ITS), massive unmanaged bleeding, and acute hepatorenal syndrome.

The convalescence period is extremely long. The patient's working capacity is restored no earlier than in one to two months, and deep functional disorders can persist for 1–2 years. After recovery, a strong immunity is formed: complement-fixing and precipitating antibodies circulate in the blood for more than 5 years.

Diagnostics, treatment, and safety measures

Several modern approaches are used for microbiological diagnosis:

• Rapid diagnostics: examination of blood, vectors, or autopsy material using indirect hemagglutination assays (IHA) and immunofluorescence assays (IFA) using monoclonal sera.
• Molecular biological methods: PCR to detect specific viral RNA and ELISA to detect pathogen antigens.
• Virological method: isolation of the virus from the blood or internal organs of the deceased by infecting newborn white mice or cell cultures followed by identification via IFA.
• Serology: screening for specific antibodies in paired sera using ELISA.

Etiotropic therapy is based on the use of antiviral drugs (Ribavirin, Reaferon). Early immunotherapy is extremely important, being effective only in the first 3 days of the disease: heterologous specific equine immunoglobulin, immune serum, plasma, or specific immunoglobulin obtained from convalescents or vaccinated individuals is administered.

Patients with suspected infection require immediate hospitalization strictly in separate isolation boxes. The reason for such isolation lies in the highest concentration of the virus in the blood, which creates a colossal risk of nosocomial spread. Only specially trained personnel are allowed to work. For risk groups (e.g., laboratory staff), specific prophylaxis is provided—formol vaccine prepared from the brains of infected newborn rats or mice.

Class and exam questions

What else to study on this topic

• Features of morphology and genetic diversity of members of the Bunyaviridae family.
• Pathogenesis of the development of generalized capillariotoxicosis and infectious-toxic shock.
• The "ping-pong" effect in virology: biochemical mechanisms of increasing pathogen virulence.
• Principles of creation and application of formol vaccines based on animal brain tissue.

Other topics in the section "Bunyaviruses (hemorrhagic fevers, hantaviruses)"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.