July 12, 2017
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Crimean-Congo hemorrhagic fever spreads to Spain

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Local transmission of Crimean-Congo hemorrhagic fever, or CCHF, has been documented in Spain for the first time, a finding that researchers said changes the geographic distribution of the frequently fatal infection.

Writing in The New England Journal of Medicine, the researchers detailed two infections that occurred last August — a man who was bitten by a tick as he walked through a field in small village in central-western Spain, and a nurse in Madrid who came in contact with the man’s blood while treating him shortly before he died.

Person-to-person transmission has been documented before, but the virus that causes CCHF is usually transmitted to humans by tick bites or through the slaughter of infected animals. WHO estimates the disease’s fatality rate at around 30%, and the CDC says documented outbreaks have killed between 9% and 50% of hospitalized patients. In 2009, CCHF killed a U.S. soldier who was stationed in Afghanistan.

Historically, CCHF has been limited by the geographic range of its tick vectors. For example, the disease is endemic in Africa, parts of Asia and the Middle East, but it had never been documented in European patients outside of countries in the eastern and southeastern parts of the continent until now. However, ticks collected in 2010 in Spain showed evidence of infection with the virus, another example of the shifting geographic ranges of some ticks.

According to the study in NEJM, the strain of CCHF recovered from the two Spanish patients shared a genetic footprint with an African lineage of the disease but did not match sequences from Eastern Europe. In their report, Jose R. Arribas, MD, of the infectious disease unit at Hospital La Paz in Madrid, and colleagues speculated about the ways infected ticks could have reached Spain, including the possibility that they arrived on birds migrating north from Morocco.

“CCHF is another example of a re-emergent virus because it has appeared in a new location previously unaffected — like Zika in the Americas,” Arribas told Infectious Disease News.

“Clinicians in Spain have to be aware that we have a new hemorrhagic fever that is autochthonous,” Arribas continued. “In other countries, it is important to monitor ticks for the presence of CCHF virus.”

The index patient in Spain was a man aged 62 years who presented at a hospital in Madrid with a 2-day history of high fever, abdominal pain, malaise, nausea and diarrhea. The man’s family said he had been bitten by a tick on the left knee 4 days earlier while walking through a field in the village of San Juan del Molinillo, which is about 75 miles outside of Madrid. Over the course of the week following his admission, the man’s condition deteriorated as he was treated in several different ICUs. He died on the ninth day of illness.

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According to Arribas and colleagues, every test for routine infections came up negative. Indeed, in their report they said that CCHF was not even considered until a nurse who treated the patient began showing similar clinical symptoms.

The nurse, a woman aged 50 years, was likely infected as she helped intubate the man and insert femoral venous and arterial catheters as he bled profusely 1 day before his death, according to the report. Her hands came in contact with the patient’s blood, but her skin was not punctured.

“It is very likely that in the absence of a second case, this outbreak of CCHF would not have been discovered,” Arribas and colleagues said. “Thus, it is possible that other cases of CCHF may have occurred in Spain in recent years.”

Beginning on the fourth day of illness, the woman was treated orally and then intravenously with ribavirin — 1,000 mg every 6 hours at first, then 500 mg every 8 hours. The treatment was discontinued after 5 days because of suspected severe hemolytic anemia. Arribas and colleagues noted that IV use of ribavirin coincided with a “rapid decline in viremia” in the patient, but they said the drug remains a controversial treatment for CCHF patients because evidence has not shown that it works.

The woman was transferred to a high-isolation unit, where infection control measures were kept in place until two consecutive blood tests on her 22nd day of illness came back negative. Among the hundreds of people who were potentially exposed by the index patient, she was the only one who became infected, according to the report.

Arribas and colleagues said the death of the index patient provided a rare opportunity to perform a human necropsy on a patient with CCHF. Among their findings, they reported the “striking” appearance of the complete epithelial denudation of the man’s colon, which they characterized as unexpected.

“This feature of the disease is unusual because it is not accompanied by multiorgan failure and suggests massive, viral-induced cell damage,” they wrote.

“Our observations highlight the importance of routine surveillance of vectors capable of spreading CCHF,” they concluded. “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.” by Gerard Gallagher

Disclosure: The researchers report no relevant financial disclosures.