Crimean-Congo Fever Reemerging, Cases Suggest

Veronica Hackethal, MD

July 12, 2017

Two cases of Crimean Congo Hemorrhagic Fever (CCHF) have been reported in Spain. Both infections were acquired within the country — the index case from a tick bite, the other while caring for the index patient — suggesting CCHF may be spreading geographically.

The case reports were published in the July 13 issue of the New England Journal of Medicine.

"Given the expanding distribution of the main vector, the appearance of these two cases in a previously unaffected region of Europe reinforces the notion that CCHF is a reemerging infectious disease," write Jose Arribas, MD, from the Hospital Universitario La Paz in Madrid, Spain, and colleagues with the Crimean Congo Hemorrhagic Fever @ Madrid Working Group.

CCHF is a viral disease spread by ticks. Humans acquire the disease through tick bites or by coming into contact with the body fluids of people or animals infected with the virus. CCHF causes severe illness, with a case-fatality rate up to 40%, according to the World Health Organization. Symptoms are similar to other hemorrhagic fevers, such as Ebola, and include fever, hepatitis, and blood clotting problems that can lead to hemorrhaging. Severe illness can cause multiorgan failure and death. No vaccine is currently available.

CCHF has been detected in more than 30 countries in Africa, Asia, the Middle East, and the southeastern part of Europe.

The index case was a 62-year-old man who acquired the disease in August 2016 from a tick bite received while walking through a field in the province of Ávila, in central-Western Spain. He was admitted to the hospital after 2 days of high fever, abdominal pain, malaise, nausea, and diarrhea. He was treated with doxycycline without improvement. His course was complicated by severe blood clotting problems, liver failure, kidney failure, severe respiratory insufficiency, encephalopathy, hypoglycemia, severe metabolic acidosis, and shock. On day 9, he died.

During the course of his illness, tests for routine infections remained negative. CCHF virus was isolated from serum samples taken on day 6.

The second patient, a 50-year-old nurse, was infected with CCHF when she came into direct contact with the index patient's blood while caring for him. On day 1, she developed fever, weakness, and muscle and joint pain. On day 4, she was started on ribavirin empirically as a result of suspected CCHF. She was later transferred to the high-level isolation unit at La Paz University Hospital. Her course was complicated by blood clotting problems, respiratory failure, increased liver enzymes, minor kidney impairment, and severe hemolytic anemia requiring blood transfusions.

During the course of her illness, urine and sweat samples remained negative for CCHF. Nasal, conjunctival, and rectal swabs were weakly positive at least once during her illness. Viral titers taken from saliva, vaginal, and rectal swabs were high enough to be quantified. The CCHF virus remained detectable in her blood until day 20. A second consecutive test on day 22 confirmed clearance of viral RNA from her blood. She was discharged from the hospital on day 25.

The local public health service conducted contact tracing for all people exposed to either patient. Although 437 people were exposed and 386 were considered high risk for CCHF, none developed symptoms.

Both patients were infected with the African 3 lineage of the virus. In Spain, this strain was first detected in 2010 in Hyalomma lusitanicum ticks found 300 km away from where the index patient received his tick bite.

The authors noted that CCHF was not suspected in the second patient until she developed symptoms similar to the index patient. If the second patient had not gotten sick, this outbreak would probably have been missed. That suggests other cases of CCHF may have occurred in Spain in recent years, but may have gone undiagnosed.

"Our observations highlight the importance of routine surveillance of vectors capable of spreading CCHF. When CCHF nucleic acid is amplified from infected ticks in geographic areas that have previously been unaffected by CCHF, clinicians should remain alert to the possibility of human cases," the authors conclude.

The study was funded by Red de Investigación Cooperativa en Enfermedades Tropicales and Efficient Response to Highly Dangerous and Emerging Pathogens at EU Level. The authors have disclosed no relevant financial relationships.

N Engl J Med. 2017;377:154-161.

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