Page 95 - JSOM Spring 2023

FIGURE 1 Hyalomma ticks, the principal vector and reservoir Nosocomial Transmission
of CCHF. and Tactical Considerations

Nosocomial transmission of CCHF to healthcare workers
remains one of the most frequently reported means of trans-
mission. The case of a US Soldier stationed in Afghanistan
13
who contracted the disease in 2009 resulted in the exposure of
18 healthcare providers. Sixteen providers received ribavirin
post-exposure prophylaxis, two of whom tested positive for
the virus but had minimal symptoms while taking ribavirin.
Those at the highest risk of infection had either reported con-
tact of skin or mucous membranes with contaminated blood
or body fluids or had been present during a bronchoscopy
without a properly fitted N95 respirator. Taken together, if
CCHF is suspected, full contact precautions to include a gown,
Adapted from Introduction to Crimean-Congo Haemorrhagic Fever. gloves, face mask, and eye shield should be deployed and up-
World Health Organization. 1
graded to airborne precautions (N95 respirator) if the patient
undergoes any potentially aerosolizing procedures. Addition-
FIGURE 2 Geographic distribution of CCHF.
ally, maximum available precautions should be taken in the
tactical transport of potentially infected Soldiers. There is no
established period of infectiousness, but reports suggest once a
patient has reached the convalescence phase and is afebrile, the
risk of transmission is reduced. 14,15 Therefore, patients should
remain isolated until fever has resolved, symptoms have im-
proved, and a minimum 10 days have passed since onset of
symptoms. The British Royal Airforce’s Deployable Air Isola-
tor Team (DAIT) has executed successful aeromedical evacua-
tion missions of patients infected with CCHF and Ebola Virus
using a specialized Trexler Air Transport Isolator. A similar US
capability, the Transport Isolation System (TIS), has recently
been developed and should be utilized for medical evacuation
of CCHF patients when available. 16,17

Pathogenesis
Adapted from Outbreak Distribution Map | Crimean-Congo Hemor-
rhagic Fever (CCHF). Centers for Disease Control. https://www.cdc. CCHFV is a member of the Nairoviridae family of Bunyavir-
gov/vhf/crimean-congo/outbreaks/distribution-map.html. 33 idae constituting an enveloped, negative-sense single-stranded
RNA virus requiring a viral RNA-dependent RNA polymerase
3 billion people are at risk of infection with an estimated to replicate. The genome consists of three segments: S, M, and
1,500 infections and 500 deaths each year. As of 2017, WHO L, named for their progressive size with key proteins includ-
1
data suggest that the Russian Federation, Uzbekestan, Turkey, ing surface glycoproteins, Gc, Gn, and GP38. 18,19 Currently the
and Iran have the highest rate of infections, with 50 or more cellular target of CCHFV is unknown, though Gc and GP38
cases reported annually. Seropositivity studies suggest many are believed to be key mediators in cellular targeting and entry
8
wild and domesticated animals can asymptomatically harbor and possible vaccine targets. 18,19
2
the virus and serve as additional reservoirs. Ostriches are the
only birds known to be infected by CCHF after an outbreak The hallmarks of CCHFV infection are vascular dysfunction,
9
in 1984 was traced to infected ostrich meat in South Africa. coagulopathy, and hemorrhage. 18,19 The exact mechanism
However, migratory birds may still spread the disease by of disease progression is poorly understood due to a lack of
carrying CCHFV-infected ticks. In addition to Hyalomma, strong animal models. 18,19 Post-mortem histologic studies sug-
10
CCHFV has also been isolated from other ticks including gest hepatocytes, endothelial cells, and monocytes comprise
11
Dermacentor. The tick acquires the virus when feeding on CCHFV infective trophism. 18–20 There is debate regarding
infected hosts. The virus replicates in the tick’s intestinal wall whether direct viral infection of endothelia or indirect vascu-
and then spreads to the salivary glands and reproductive or- lar damage through cytokine release is the key mediator of
gans. As a result, Hyalomma ticks spread CCHFV via hor- disease, though evidence suggests a systemic inflammatory re-
2
izontal and vertical transmission through bites and infected sponse akin to bacterial sepsis drives vascular leakage and co-
larval offspring. The Hyalomma tick remains infectious to agulopathy. 18,19 Severe disease is often accompanied by marked
2
2
humans at all stages of its lifecycle. It is not clear how long elevations in transaminases, prothrombin time (PT), activated
a tick must remain attached to transmit the virus. As such, a partial thromboplastin time (aPTT), lactate dehydrogenase
tick with any level of engorgement should be considered a (LDH), tumor necrosis factor alpha (TNF-α), and interleukins
true exposure. In addition to tick bites, humans may be in- 1 (IL-1) and 6 (IL-6) suggesting inflammatory mediation of
fected via direct contact with animal blood or other infected disease. A combination of hepatic synthetic dysfunction and
tissue – many reported cases occur in farmers, slaughterhouse immune-mediated vascular damage leads to disseminated in-
workers, and butchers. Sexual transmission of CCHF also travascular coagulation (DIC), cytopenias, profound vascular
2
appears possible. 12 leak, hemorrhage, and shock. 18,19,21–23 Studies of interferon
Crimean-Congo Hemorrhagic Fever | 93