Quantifying and Modeling the Acquisition and Retention of Lumpy Skin Disease Virus by Hematophagus Insects Reveals Clinically but Not Subclinically Affected Cattle Are Promoters of Viral Transmission and Key Targets for Control of Disease Outbreaks

Abstract

Lumpy skin disease virus (LSDV) is a vector-transmitted poxvirus that causes disease in cattle. Vector species involved in LSDV transmission and their ability to acquire and transmit the virus are poorly characterised. Using a highly representative bovine experimental model of lumpy skin disease we fed four model vector species (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus) on LSDV-inoculated cattle in order to examine their acquisition and retention of LSDV. Subclinical disease was a more common outcome than clinical disease in the inoculated cattle. Importantly, the probability of vectors acquiring LSDV from a subclinical animal (0.006) was very low compared to acquisition from a clinical animal (0.23), meaning an insect feeding on a subclinical animal was 97% less likely to acquire LSDV than one feeding on a clinical animal. All four potential vector species studied acquired LSDV at a similar rate from the host, but Aedes aegypti and Stomoxys calcitrans retained the virus for a longer time, up to 8 days. There was no evidence of virus replication in the vector, consistent with mechanical rather than biological transmission. The parameters obtained in this study were combined with data from studies of LSDV transmission and vector life history parameters to determine the basic reproduction number of LSDV in cattle mediated by each of the model species. This was highest for Stomoxys calcitrans (19.1), C. nubeculosus (7.1), and Ae. aegypti (2.4), indicating these three species are potentially efficient transmitters of LSDV, which can be used to inform LSD control programmes. Importance: Lumpy skin disease virus (LSDV) causes a severe systemic disease characterised by cutaneous nodules in cattle. LSDV is a rapidly emerging pathogen, having spread since 2012 into Europe and Russia, and across Asia. The vector-borne nature of LSDV transmission is believed to have promoted this rapid geographic spread of the virus, however a lack of quantitative evidence about LSDV transmission has hampered effective control of the disease during the current epidemic. Our research shows subclinical cattle play little part in virus transmission relative to clinical cattle, and reveals a low probability of virus acquisition by insects at the pre-clinical stage. We have also calculated the reproductive number of different insect species, therefore identifying efficient transmitters of LSDV. This information is of utmost importance, as it will help to define epidemiological control measures during LSDV epidemics and of particular consequence in resource-poor regions where LSD vaccination may be less than adequate.

Detection of Clinical and Subclinical Lumpy Skin Disease Using Ear Notch Testing and Skin Biopsies

“…LSD typically induces characteristic skin nodules and lesions on mucosal surfaces. The mechanical transmission of LSDV from clinically infected animals by several blood feeding insects has been demonstrated [ 5 , 6 , 26 , 27 , 28 ]. However, LSDV infection may range from clinical disease (severe and generalized) to subclinical (asymptomatic).…”

“…However, LSDV infection may range from clinical disease (severe and generalized) to subclinical (asymptomatic). Even when animals are experimentally infected, subclinical infection can occur in a significant proportion of the animals [ 6 ]. A recent quantifying and modeling study estimated that the role of subclinical cattle in LSDV transmission is minimal relative to clinical cattle [ 6 ], but the real importance of subclinical infection in transmission of LSDV in vivo should still be determined.…”

“…The severity of the clinical disease is often influenced by the animal’s age, breed, immune status and production period [ 1 ]. The main mode of transmission of LSDV is mechanical via blood-feeding insects with frequent feeding habits [ 5 , 6 ], although the main vector is likely to vary between geographical regions and ecosystems [ 1 ]. LSD diagnosis is primarily based on the clinical diagnosis of LSD, confirmed by the PCR analysis of lesion crusts or biopsies of the nodules or affected skin [ 7 ].…”

“…However, LSDV infection is not always apparent, as mild and subclinical disease occur. Even when cattle are experimentally infected, up to 50% of animals remain uninfected or subclinically infected [ 5 , 6 , 8 , 9 , 10 ].…”

“…In addition, awareness campaigns, vector control, increased farm biosecurity and clinical surveillance programs are needed to avoid (re-)introduction. Since LSD can be mild and subclinical [ 5 , 6 ], the sensitivity of clinical surveillance could be lower than expected and must therefore be complemented with laboratory diagnosis [ 7 ]. However, farmers are reluctant to have biopsies taken.…”