Page 96 - JSOM Spring 2023

(IFN) knockout mice suggest the innate immune system plays geographic distribution and enforce vigilant tick and insect
19
a key role in limiting disease. Reports have also shown that control measures (DEET chemical repellent, long sleeves, and
failure to mount a humoral immune response (IgG/IgM) cor- daily tick checks) in the deployed environment. Additionally,
relates with fatal disease. 18,19 SOF providers should counsel their operators on the viral life
cycle and transmissibility of CCHFV from livestock. In the
evaluation of any patient with suspected viral hemorrhagic fe-
Clinical Disease and Diagnosis
ver in the deployed environment, the highest level of personal
The incubation period of CCHF lasts one to three days af- protective equipment available should be maintained. 2,3,27 Any
ter tick exposure, and 5–6 days after blood exposure. 1,2,24 patients exposed should be quarantined for 14 days and con-
Once symptoms develop, CCHF generally progresses through firmed cases should be isolated for a minimum of 10 days and
three phases: pre-hemorrhagic, hemorrhagic, and conva- until symptoms improve and fever has resolved.
lescence (Figure 3, created with BioRender.com). 1,2,24 In the
pre- hemorrhagic period, the symptoms are nonspecific, and Post-exposure prophylaxis (PEP) and early treatment with
patients develop generalized myalgias, fevers, nausea, vomit- ribavirin, a nucleoside analogue viral polymerase inhibitor,
ing, and diarrhea. 1,2,24 This period lasts 1–7 days and patients may provide benefit. 3,4,13,27 Recently, Ergonul et. al performed
may begin to develop leukopenia and thrombocytopenia. 1,2,24 a meta-analysis of reports published between 1976 and 2017
At approximately day 7 of symptom onset, the hemorrhagic examining post-exposure prophylaxis and early treatment for
phase begins. 1,2,24 Patients may develop hematemesis, me- CCHF in healthcare workers: among 175 exposed healthcare
13
lena, somnolence, and cutaneous bleeding from various sites workers, 55 (31%) received PEP. Infection rates among those
and diffuse ecchymosis. 1,2,24 Thrombocytopenia and leuko- who did and did not receive PEP were 7% and 89%, respec-
penia worsen while transaminases rise and coagulation is tively. Further, none of the 17 patients treated with ribavirin
deranged. 1,2,24 The hemorrhagic period lasts approximately within 48 hours died, while 42% of those who did not receive
3 days with death occurring most commonly around day 10 treatment died. Ribavirin reduced the odds of infection (OR
of symptom onset. 1,2,24 While mortality rates reportedly range 0.01, 95% CI 0–0.03) and when given within 48 hours, re-
from 5–30%, seroprevalence studies suggest that a significant duced the odds of death (OR 0.03, 95% CI 0.0–0.58). The
13
number of cases develop few or no symptoms and therefore US Army Medical Research Institute of Infectious Diseases
2,7
may go unreported. For those who survive, fever abates and (USAMRIID) recommends the use of ribavirin for both PEP
gives way to the convalescence phase. and the treatment of CCHF (Table 1). The most common
27
adverse reactions to ribavirin include fatigue, pyrexia, myalgia
FIGURE 3 Disease progression of CCHF. 28
and headache. Ribavirin is extremely teratogenic and should
28
not be given to pregnant women. Ribavirin can also cause
hemolytic anemia and should not be given to patients with
hemoglobinopathies. 28
TABLE 1 Prophylactic and Therapeutic Ribavirin for CCHF
Post-Exposure Prophylaxis
• Ribavirin 500 mg PO qid for 7 days (for those in contact with
patient within 3 weeks of onset of illness)
Treatment with PO Ribavirin (off label use)
• 2g loading dose, then 1g q6h x 4 days, then 0.5g q6h x 6 days
Treatment with IV Ribavirin (investigational new drug)
Adapted from Introduction to Crimean-Congo Haemorrhagic Fever.
World Health Organization. https://www.who.int/publications/i/item/ • 33mg/kg loading dose, then 16mg/kg q6h for 4 days, then
introduction-to-crimean-congo-haemorrhaigc-fever 1 8mg/kg q8h for 6 days
QID = four times/day, PO = oral, q6h = every six hours, q8h = every
The differential diagnosis should be honed by exposure history eight hours, IV = intravenous
and includes other viral hemorrhagic fevers, malaria, dengue, Adapted from USAMRIID Pocket Reference Guide: Biological Select
and typhoid fever. CCHF should be suspected in patients in an Agents and Toxins. 3
endemic region with possible tick or animal exposure. Diagno-
sis can be confirmed with a serum polymerase chain reaction Aside from prevention and antivirals, supportive care remains
(PCR) test in the first 10 days after the onset of symptoms. 1,2,24 a critical component to the management of CCHF. Support
IgM antibodies are detectable from 7 days to four months after should focus on addressing coagulopathy and bleeding with
infection, while IgG remains elevated for years. 1,2,24 There are blood product transfusions, monitoring and support of renal
currently no rapid point-of-care tests for CCHF, though they function and electrolyte abnormalities, and cardiopulmonary
are under development. A scoring system for severity has been support. Evaluation for concomitant infection is reasonable
25
developed to aid in the triage of patients with CCHF. However, depending on epidemiologic risk factors.
in the deployed or austere environment, any patient suspected
of CCHF should be isolated and transferred to a higher level of While a Soviet formulated vaccine derived from infected
care. Recovery is often prolonged, so patients and potentially mouse brains has been in use in Bulgaria since 1974, there
26
29
exposed patients should not be kept in the field. are no globally recognized vaccines for CCHF. Efforts for a
CCHF vaccine have previously been stymied by poor animal
models and lack of protection, despite the development of neu-
Medical Countermeasures tralizing antibodies. Several vaccine candidates currently in
29
Prevention is the primary medical countermeasure in com- development have shown promise. 29,30 Additionally, a recent
bating CCHF. SOF providers should be familiar with the study performed in collaboration with USAMRIID identified
94 | JSOM Volume 23, Edition 1 / Spring 2023