Cache Valley virus: A scoping review of the global evidence

Abstract

Cache Valley virus (CVV) is a mosquito‐borne RNA virus detected throughout North America, Central America and parts of South America. A limited number of human case reports have described severe illness. CVV infection has been associated with outbreaks of congenital defects in small ruminants in Canada and the United States. A scoping review was conducted to identify, characterize and summarize research on CVV, and to identify research gaps. A structured search was conducted in eight electronic databases, with additional search verification and grey literature investigation. All captured studies were independently appraised by two reviewers for relevance and data characterization. The review captured 143 relevant studies investigating CVV epidemiology (n = 104), pathogenesis (n = 37), viral characteristics (n = 24), transmission (n = 14), diagnostic test performance (n = 8) and mitigation strategies (n = 2). Evidence of CVV infection was found in mosquito studies (n = 47), and serological evidence of exposure was demonstrated in animals (n = 41), as well as human (n = 20) studies. In sheep, five outbreaks of birth defects following asymptomatic dam CVV infection during the first 50 days of pregnancy were reported. Only six human cases of CVV‐associated illness were captured, with case symptoms described as initially non‐specific, progressing to more severe clinical signs (e.g., meningitis). No research was identified investigating treatment, societal knowledge and risk perception, economic burden or predictive models related to the impact of climate change on CVV. CVV circulates in mosquito and animal species across a large area of the Americas. Small ruminants are the only animals in which CVV‐associated clinical disease has been extensively studied. It is likely that human cases are under‐reported or misdiagnosed. Future research should focus on the impact of CVV infection in human and animal populations.

Novel murine models for studying Cache Valley virus pathogenesis andin uterotransmission

“…CVV has an extraordinarily wide host range and has previously been serologically detected or isolated from several domestic animals including sheep ( Ovis aries) , goats ( Capra hircus ), cattle ( Bos taurus) , horses ( Equus caballus ), swine ( Sus scrofus ), rabbits (family Leporidae), and guinea pigs ( Cavia porcellus ) [ 7 , 9 ]. There is strong evidence that CVV transmission can be maintained in horses ( Equus caballus ) [ 10 ], swine, goats, [ 11 ], elk ( Cervus canadensis ) [ 12 ], and white-tailed deer ( Odocoileus virginianus ) which are suspected to be the primary amplification host [ 13 , 14 ].…”

“…Rates were as high as 96.7% in the eastern U.S., to 53.3% in the central U.S., and 58.9% in the Western U.S. [ 15 ]. CVV infections have been reported in humans [ 9 , 16–19 ] and seroprevalence rates in humans have been shown to be as high as 40% [ 9 , 19–22 ]. The virus is known to cause disease in humans, including fever, headaches, nausea, fatigue, encephalitis, meningitis, spontaneous abortions, and macrocephaly in infants [ 17–20 , 23 , 24 ].…”

Identification of animal hosts of Fort Sherman virus, a New World zoonotic orthobunyavirus

“…The reassortant FSV prototype strain originated from Panama and consists of FSV-related L and S segments with a CVV-related M segment. Because CVV circulates in Northern America (Calisher et al, 1986;Waddell et al, 2019), and our data show wide circulation of FSV in Southern America, it seems feasible that a reassortant virus would emerge in Central America, where the two subcontinents are connected. Since orthobunyaviruses show frequent reassortment events (Briese, Calisher, & Higgs, 2013), it will be interesting to see whether this potential geography-driven reassortment pattern can also be observed in other American orthobunyaviruses in future studies.…”

Fatal Progressive Meningoencephalitis Diagnosed in Two Members of a Family With X-Linked Agammaglobulinemia

“…In two adolescents with XLA and progressive encephalitis, astrovirus, a single-stranded enteric RNA virus causing mild gastroenteritis in humans, had been identified in the brain tissue by the use of novel molecular technologies, including unbiased high-throughput pyrosequencing and next generation sequencing ( 22 , 23 ). Cache valley virus, a mosquito-borne orthobunyavirus, detected throughout North America, Central America, and parts of South America ( 24 ), was identified by the use of metagenomic next generation sequencing in the CSF and brain biopsy tissue in an Australian adult patient with XLA who developed chronic meningoencephalitis after travel to the United states ( 25 ). To investigate the etiological microorganism in our index patient, we utilized the RDV method ( 12 , 26 ), an unbiased molecular method that detects RNA viruses, but failed to identify any causative viruses.…”