Monday, June 17, 2019

Epidemics: Systematic Review Of MERS-CoV Seroprevalence and RNA Prevalence in Dromedary Camels

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We are rapidly approaching the 7th anniversary of the discovery of the MERS-CoV virus - first isolated from a patient in Saudi Arabia - and it's been 6 years since camels were identified as a host species (see 2013's The Lancet Camels Found With Antibodies To MERS-CoV-Like Virus).
While bats are suspected to be the primary host reservoir for MERS, SARS, and an array of other novel pathogens (see Curr. Opinion Virology: Viruses In Bats & Potential Spillover To Animals And Humans), camels - due to their close contact with people in the Middle East - are the main conduit by which the virus appears to spillover to humans.
Despite some early optimism (see 2013's mBio: Engineered MERS Strain For Vaccine Research), six years have passed and an effective, commercially available vaccine remains elusive.

As we discussed last month in Manufacturing Pandemic Flu Vaccines: Easier Said Than Done, cobbling together a vaccine for a novel virus isn't nearly as easy as the media, and fiction writers, would have us believe.
Despite 16 years of research, no commercially available SARS vaccine has been developed, and twenty years after its discovery, a Nipah vaccine is still in the works.
As camels are the logical target for any vaccine, understanding how MERS spreads, and infects, dromedaries is key (see Epi.& Inf.: Global Status Of MERS-CoV In Camels - A Systemic Review). But many questions remain, including:
  • Why 100% of the known and suspected camel-to-human transmissions have been recorded on the Arabian peninsula, while the MERS virus and antibodies have been detected in camels from both Africa and South-Central Asia. 
  • Why roughly 90% of Middle Eastern human MERS infections have been reported by one country; Saudi Arabia
  • Why spillover from camels appears to peak in the winter and spring
  • And why human cases were never identified before 2012, despite evidence of MERS circulation in camels going back at least 30 years.
Complicating the quest for a MERS vaccine even further, in 2017's  MERS-CoV In Camels: The Gift That Keeps On Giving, we saw a study that showed  that camels can be reinfected by the MERS virus, despite having substantial antibody titers.

While this raises concerns over the ability of a vaccine to prevent infection, it may still be that a vaccine could lower viral shedding, and reduce the risks of zoonotic transmission. But for now, there are more questions than answers. 
All of which brings us to a detailed, data-heavy, open-access systematic review of Dromedary camel infection with the MERS virus in Africa, Asia, and the Middle East, and that discusses potential pitfalls in vaccine development.
By definition this review covers a good deal of previously trod ground, but it provides an excellent overview of our current understanding of how (and where) MERS circulates in camels, and some of the obstacles we may face in producing an effective MERS vaccine.

Follow the link to read it in its entirety, after which I'll have a brief postscript:

A systematic review of MERS-CoV seroprevalence and RNA prevalence in dromedary camels: Implications for animal vaccination
AmyDighe a ThibautJombart abc Maria D.Van Kerkhove d NeilFerguson a

https://doi.org/10.1016/j.epidem.2019.100350

Highlights

  • Most adult dromedaries in Africa and the Middle East have been infected with MERS-CoV.
  • Seroprevalence increases with age, while active infection is more common in calves.
  • Prevalence is higher at sites where different dromedary populations mix
  • Further study is needed to determine if prevalence of infection varies seasonally.

Abstract

Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination.
Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We aim to bring together existing measures of MERS-CoV infection in dromedary camels to assess the distribution of infection, highlighting knowledge gaps and implications for animal vaccination.
We systematically reviewed the published literature on MEDLINE, EMBASE and Web of Science that reported seroprevalence and/or prevalence of active MERS-CoV infection in dromedary camels from both cross-sectional and longitudinal studies. 60 studies met our eligibility criteria.
Qualitative syntheses determined that MERS-CoV seroprevalence increased with age up to 80–100% in adult dromedaries supporting geographically widespread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design and evaluation through mathematical modelling.
       (SNIP)
Conclusions

Our findings provide strong evidence that MERS-CoV is endemic in dromedary populations across much of West, North, East Africa and the Middle East, in agreement with the similar systematic review conducted in parallel with our own (Sikkema et al., 2019).

In addition, our findings highlight several epidemiological characteristics of MERS-CoV that must be considered in the design of MERS-CoV animal vaccination strategies.
Calves are likely to play a central role in sustaining circulation of MERS-CoV and should be a target of potential dromedary vaccination.
However, the potential for mass vaccination of calves to change the age distribution of infected individuals should be investigated through mathematical modelling of transmission dynamics in dromedary populations and considered in the context of age-dependent human-camel contact frequency patterns.
Sites where dromedaries mix may also play a role in driving transmission. A better understanding of dromedary husbandry and trade patterns, as well as quarantine facilities, is needed to identify where dromedaries become infected with MERS-CoV – critical for focussing potential vaccination strategies both geographically and within the dromedary camel value chain.
Although in a few studies, prevalence of infection appears to peak in the first half of the year, which may be facilitated by the increase in susceptible animals after the calving season, further studies are needed to confirm this. More longitudinal studies are required to investigate the temporal dynamics of viral shedding and immunity in the animal host and should ideally be capable of distinguishing co-circulating MERS-CoV lineages.

The remaining gaps in our understanding of MERS-CoV transmission dynamics in dromedary populations are in agreement with the prioritized research outlined in the FAO-OIE-WHO Technical Working group report (FAO-OIE-WHO MERS Technical Working Group, 2018) and must be addressed to obtain a clearer picture of what an optimal epidemiological vaccination strategy would involve, as well as its likely impact, before wider challenges of implementation can be considered further.
       (Continue. . .  )


Some previous blogs on MERS-CoV in camels include:

Emerg. Microbes & Inf.: Bactrian Camels Shed Large Quantities of MERS-CoV After Experimental Infection
mBio: High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia
Eurosurveillance: Lack of Serological Evidence of MERS-CoV In Camel Abattoir Workers - Nigeria 2016

EID Journal: Geographic Distribution of MERS-CoV among Dromedary Camels, Africa
EID Journal: Serologic Evidence Of MERS-CoV Infection in Pakistani Camels