Quantifying and modelling the acquisition and retention of lumpy skin disease virus by haematophagus insects reveals clinically but not subclinically-affected cattle are promoters of viral transmission and key targets for control of disease outbreaks

Abstract

Robust transmission parameters are required in order to control infectious diseases. With a novel approach, we combine in vivo experimental studies with mathematical modelling to estimate transmission parameters of lumpy skin disease virus (LSDV), a vector-transmitted poxvirus of cattle, including the relevance of four potential vector species (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus). The probability of LSDV transmission from clinical cattle to the vector correlated with disease severity, and was very low when subclinical animals were considered. All four vector species tested had a similar rate of acquisition of LSDV after feeding on the host, retaining the virus for up to 8 days. We combined our experimental results with other published data on LSDV transmission and vector life history to determine the basic reproduction number of LSDV in cattle mediated by each of the model species, which can be used to inform LSD control programmes.Haematophagus dipterans (referred to in this work as "blood-feeding insects"), particularly Stomoxys calcitrans, have been associated with outbreaks of LSDV 7,18-20 . In addition, experimental transmission of LSDV from affected to naïve animals (defined by the presence of clinical disease and/or detection of systemic LSDV antigen and/or capripoxvirus-specific antibodies) has being demonstrated via the mosquito Aedes aegypti 21 , the ticks Rhipicephalus appendiculatus 22-24 , Rhipicephalus decoloratus 25 , Amblyomma hebraeum 26 , the stable fly Stomoxys calcitrans, horseflies Haematopota spp. and other Stomoxys species 27,28 . LSDV DNA has also been detected in other species after feeding on infected cattle or on an infectious blood meal (Culex quinquefasciatus, Anopheles stephensi, Culicoides nubeculosus) 29 , or in field-caught pools (Culicoides punctatus) 4 . However transmission of LSDV to susceptible 4 of 45animals has not been confirmed for these species. To date the mode of LSDV arthropod transmission has been assumed to be mechanical as no evidence of active virus replication in insects or ticks has been found 30 .LSDV can be detected in skin lesions, blood (primarily in peripheral blood mononuclear cells), and in nasal, oral and ocular excretions of infected cattle 27,31,32 . Viraemia is considered of short duration and relatively low level, though the virus can survive for longer periods of time in skin lesions 31 . LSDV has also been detected in seminal fluid of diseased bulls 33 , making venereal transmission a possibility [34][35][36] . Subclinical infections (detection of LSDV in animals without cutaneous lesions) 3,27,32 and resistance to LSDV (absence of LSDV and cutaneous lesions following experimental challenge) have been reported, but both are poorly documented.The contribution of subclinical LSD to the transmission of the virus is unclear and a topic of controversy when implementing control measures such as whole-herd culling, particularly when morbidity is low 37,38 .In this study we calculated biologically relevant...

A novel strain of lumpy skin disease virus causes clinical disease in cattle in Hong Kong

“…It is caused by infection with the poxvirus lumpy skin disease virus (LSDV), a member of the capripoxvirus genus. LSDV is transmitted by hematophagous vectors, such as mosquitoes and flies, which facilitate rapid spread of the virus in optimal climatic conditions (Sanz‐Bernardo et al., 2021). LSDV is a rapidly emerging pathogen, having spread over the past ten years from Africa and the Middle East into south‐east Europe, the Caucasus, Russia and, more recently, Asia (Acharya & Subedi, 2020; Beard, 2016; Calistri et al., 2020; Kumar et al., 2021; Lu et al., 2020; Sudhakar et al., 2020).…”

A novel strain of lumpy skin disease virus causes clinical disease in cattle in Hong Kong

“…It is caused by infection with the poxvirus lumpy skin disease virus (LSDV), a member of the capripoxvirus genus. LSDV is transmitted by haematophagous vectors such as mosquitoes and flies which facilitates rapid spread of the virus in optimal climatic conditions [1]. LSDV is a rapidly emerging pathogen, having spread over the past ten years from Africa and the Middle East into south east Europe, the Caucasus, Russia and, more recently, Asia [2–7].…”

The immune response to lumpy skin disease virus in cattle is influenced by inoculation route

“…The untreated animal in each experiment was not inoculated. In all three experiments blood-feeding arthropods were fed on the skin of some of the inoculated calves as described previously (11, 18, 50).…”

“…The pathology is focused on the skin as a multifocal dermatitis with vasculitis of dermal blood vessels, resulting in full-thickness necrosis of the dermis and epidermis (11). Unusually for a poxvirus, direct transmission of LSDV is rarely documented however LSDV can be transmitted by hematophagous arthropods including Aedes aegypti mosquitoes, Rhipicephalus microplus ticks and Stomoxys calcitrans stable flies (14,(16)(17)(18)(19)(20). The main methods for the control and prevention of LSDV are effective surveillance programmes to detect outbreaks, widespread use of live attenuated vaccines, and 'stamping out' of infected herds (20)(21)(22).…”

“…calcitrans and Ae. aegypti), a route which is more representative of virus transmission in the field (18). In-depth data was obtained that characterises the adaptive immune response to LSDV, correlates differences with clinical outcome, and provides critical insight into the progression of disease in the host.…”