Alkhurma Hemorrhagic Fever in Travelers Returning from Egypt, 2010

Carletti, Fabrizio; Castilletti, Concetta; Di, Antonino; Capobianchi, Maria Rosaria; Nisii, Carla; Suter, Fredy; Rizzi, Marco; Tebaldi, Alessandra; Goglio, Antonio; Tosi, C; Ippolito, Giuseppe

doi:10.3201/eid1612.101092

Cited by 68 publications

(38 citation statements)

References 11 publications

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“…KFDV was first isolated in 1957 [5]–[7] and causes outbreaks with 400–500 cases annually in Karnataka State, western India. AHFV was first isolated in 1995 [8]–[10] and has caused recent outbreaks of febrile disease in Saudi Arabia [11], [12], as well as illness in travellers returning to Europe from southern Egypt [13]. KFDV infection is primarily associated with bites from Haemaphysalis ticks [14], [15], while AHFV is thought to be transmitted by Ornithodoros savignyi and Hyalomma dromedarii ticks [16], [17].…”

Section: Introductionmentioning

confidence: 99%

Comparative Pathogenesis of Alkhumra Hemorrhagic Fever and Kyasanur Forest Disease Viruses in a Mouse Model

et al. 2014

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Kyasanur Forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (AHFV) are genetically closely-related, tick-borne flaviviruses that cause severe, often fatal disease in humans. Flaviviruses in the tick-borne encephalitis (TBE) complex typically cause neurological disease in humans whereas patients infected with KFDV and AHFV predominately present with hemorrhagic fever. A small animal model for KFDV and AHFV to study the pathogenesis and evaluate countermeasures has been lacking mostly due to the need of a high biocontainment laboratory to work with the viruses. To evaluate the utility of an existing mouse model for tick-borne flavivirus pathogenesis, we performed serial sacrifice studies in BALB/c mice infected with either KFDV strain P9605 or AHFV strain Zaki-1. Strikingly, infection with KFDV was completely lethal in mice, while AHFV caused no clinical signs of disease and no animals succumbed to infection. KFDV and high levels of pro-inflammatory cytokines were detected in the brain at later time points, but no virus was found in visceral organs; conversely, AHFV Zaki-1 and elevated levels of cytokines were found in the visceral organs at earlier time points, but were not detected in the brain. While infection with either virus caused a generalized leukopenia, only AHFV Zaki-1 induced hematologic abnormalities in infected animals. Our data suggest that KFDV P9605 may have lost its ability to cause hemorrhagic disease as the result of multiple passages in suckling mouse brains. However, likely by virtue of fewer mouse passages, AHFV Zaki-1 has retained the ability to replicate in visceral organs, cause hematologic abnormalities, and induce pro-inflammatory cytokines without causing overt disease. Given these striking differences, the use of inbred mice and the virus passage history need to be carefully considered in the interpretation of animal studies using these viruses.

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Section: Introductionmentioning

confidence: 99%

Comparative Pathogenesis of Alkhumra Hemorrhagic Fever and Kyasanur Forest Disease Viruses in a Mouse Model

et al. 2014

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“…Almost 40 years later in 1994, AHFV was isolated from a fatally infected butcher in Makkah, Saudi Arabia. Since then, AHFV cases have been confirmed in Jeddah, Jizan, and Najran in Saudi Arabia and most recently across the Red Sea, near the Egypt-Sudan border in 2010 [8].…”

Section: Introductionmentioning

confidence: 99%

Kyasanur Forest Disease Virus Infection in Mice Is Associated with Higher Morbidity and Mortality than Infection with the Closely Related Alkhurma Hemorrhagic Fever Virus

et al. 2014

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BackgroundKyasanur Forest disease virus (KFDV) and Alkhurma hemorrhagic fever virus (AHFV) are closely related members of the Flavivirus genus and are important causes of human disease in India and the Arabian Peninsula, respectively. Despite high genetic similarity, the viruses have distinctly different host ranges and ecologies. Human cases of KFDV or AHFV develop a spectrum of disease syndromes ranging from liver pathology to neurologic disease. Case reports suggest KFDV is more commonly associated with hepatic and gastrointestinal manifestations whereas AHFV is more commonly associated with neurologic disease.Methodology/Principal FindingsInoculation of three immunocompetent laboratory mouse strains revealed that KFDV was consistently more lethal than AHFV. In subsequent studies utilizing C57BL/6J mice, we demonstrated that KFDV infection was associated with higher viral loads and significantly higher mortality. KFDV-infected mice rapidly developed more severe disease than AHFV-infected mice, as evidenced by significant abnormalities on clinical chemistry panels and more severe pathology in the brain and gastrointestinal tract.Conclusions/SignificanceInfections of C57BL/6J mice with KFDV or AHFV resulted in clinical disease syndromes that closely approximate the diseases seen in human cases. Despite high genetic similarity, there were clear differences in survival, viral kinetics, clinical chemistry data and histology. These results suggest that distinct mouse models for AHFV and KFDV are necessary in order to gain a better understanding of the unique pathogenesis of each virus, as well as to provide platforms for testing promising vaccines and therapeutics.

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“…Furthermore, AHFV has been identified in Ornithodoros savignyi soft ticks and Hyalomma dromedarii hard ticks (potential vectors) in Saudi Arabia, both of which are associated with camels (potential reservoir) ( 4 , 5 ). Alkhurma hemorrhagic fever is endemic in several provinces of Saudi Arabia; sporadic cases have been reported in Africa near the Egypt–Sudan border and cases of seropositivity in Djibouti ( 6 – 8 ) (Figure 1). AHFV RNA has also been detected in Amblyomma lepidum ticks collected from cattle in Djibouti ( 9 ).…”

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confidence: 99%

“…Also, other pathogens have been found to disseminate by means of ticks on migratory birds ( 10 ). In light of these findings, case reports in Africa ( 6 – 8 ), and increasing case frequency in Saudi Arabia ( 11 ), we investigated whether ticks infesting migratory birds en route from Africa to Europe and Asia during springtime carry AHFV.…”

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confidence: 99%

Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor

Hoffman¹,

Lindeborg²,

Barboutis³

et al. 2018

Emerg. Infect. Dis.

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Alkhurma Hemorrhagic Fever in Travelers Returning from Egypt, 2010

Cited by 68 publications

References 11 publications

Comparative Pathogenesis of Alkhumra Hemorrhagic Fever and Kyasanur Forest Disease Viruses in a Mouse Model

Comparative Pathogenesis of Alkhumra Hemorrhagic Fever and Kyasanur Forest Disease Viruses in a Mouse Model

Kyasanur Forest Disease Virus Infection in Mice Is Associated with Higher Morbidity and Mortality than Infection with the Closely Related Alkhurma Hemorrhagic Fever Virus

Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor

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