Infectious Disease

A 64-year-old man from Italy spent 1 week in a touristic village in southern Egypt during April 2010. On April 29, he visited the famous camel market in Shalatin, the largest in Egypt and by some estimates the largest in Africa.

While there, he was bitten on the foot by a unidentified arthropod (although not formally identified, later described by him as tick-shaped). Soon after, a small, papular lesion developed. During his return flight to Italy — some 48 hours after the bite — the patient experienced high fever, shaking chills, anorexia, malaise, nausea, vomiting and blurred vision.

Arnon Shimshony

During the next 5 days, these signs and symptoms worsened, and the man was admitted to a hospital in northern Italy. Laboratory test results indicated leucopenia, thrombocytopenia and elevated liver enzymes. The patient was treated symptomatically and discharged 11 days after, in good general condition despite persistence of asthenia. Acute-phase and convalescent-phase serum samples were tested for dengue and West Nile virus, which were excluded.

Sequence analysis of the amplicon showed high similarity with the Alkhurma hemorrhagic fever virus (AHFV) sequences in the GenBank database. This unexpected result called for further investigations that eventually led to the confirmed diagnosis of AHFV infection.

One month later, AHFV was diagnosed in another Italian who visited the same camel market on the same day but was affected by a milder disease. These have become the first cases of AHFV infections reported outside the Arabian Peninsula, justifying further veterinary and entomologic investigations to determine the geographic distribution of the virus.

AHFV was initially discovered in Saudi Arabia in 1995 in an acutely and fatally ill butcher exhibiting viral hemorrhagic fever symptoms. Although the butcher was based in Makkah, where he was occupationally exposed to the suspected virus-carrying sheep, the virus was named after Alkhurma, a small settlement from where the sheep originated. Diagnostic testing identified a avivirus as the etiologic agent. Later in 1995, AHFV was isolated from the blood of six male butchers in Jeddah. Two of the patients died and the other four completely recovered. Four more patients were diagnosed serologically. The virus was confirmed by the polymerase chain reaction at the CDC.

All infected patients had similar clinical and laboratory signs and symptoms, including fever, headache, generalized body aches, arthralgia, anorexia, vomiting, leucopenia, thrombocytopenia, elevated liver enzymes, elevated creatinine phosphokinase and elevated blood urea.

One patient developed symptoms of encephalitis but survived without any sequel. Skin rash developed in two patients: morbilliform on the hands, feet and lower abdomen of one patient; and purpuric associated with melaena in the second patient. Eight of the 10 confirmed patients were working with sheep, and the disease was consequently suspected to be a zoonotic viral infection.

AHFV is a flavivirus (89% sequence homology) that is similar to another tick-borne virus — Kyasanur Forest disease virus — endemic in Karnataka, India. This genus includes more than 70 viruses, a large number of which are arthropod-borne, infecting humans and animals.

Data from ongoing epidemiological investigations and a retrospective case series strongly suggest that AHFV is a zoonotic disease; clinical cases have been epidemiologically linked to exposure to livestock (camels and sheep) and incriminate occupational exposure as a risk factor. At-risk occupations include livestock herdsmen and live-animal retailers. Housewives and young women generally involved in preparing meat at home before cooking have also been found to be at risk. Other risk factors include living in neighborhoods with livestock, tick bites and drinking unpasteurized milk. There have been fears of nosocomial transmission of AHFV within hospital settings and community-based human-to-human transmission. However, to date, no such cases have been documented.

There is a large body of evidence indicating that AHVF is a tick-borne avivirus. However, studies are lacking that give details on which tick species are the main vectors for AHFV and how these species interact with their various biotypes promoting zoonotic transmission.

The first detection of AHFV was in the soft tick Ornithodoros savignyi, when viral RNA was detected in ticks collected from a camel resting place southeast of Jeddah. AHFV has also been detected in Hyalomma dromedarii ticks taken from camels in Jeddah. Although one study has hypothesized the mosquito-borne nature of AHFV, the data available on the virology of AHFV strongly indicate that it is a tick-borne virus.

AHFV has yet to be isolated from animals; neither antibodies nor AHFV RNA have been detected in nonhuman vertebrates. This is due to the lack of studies in livestock or in small domestic, stray and wild animals, which may also serve as hosts or blood-meal sources for the immature and mature stages of putative soft and hard tick vectors. In this respect, and in the clinical picture, there are similarities between AHFV and Crimean-Congo hemorrhagic fever. Diagnosis is based upon virus isolation, nucleic acid detection and serology.

It would be advisable to inform travelers about the danger of coming into contact with infected animals in areas where the virus has been reported. Avoidance of or minimization of exposure to infected ticks should be recommended.

For more information:

• Carletti F. Emerg Infect Dis. 2010;16:1979-1982.
• Memish ZA. Int J Antimicrob Agents. 2010;36(suppl 1):S53-57.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.