Thursday, September 25, 2014

EID Journal: Replication & Shedding Of MERS-CoV In Inoculated Camels

Photo: ©FAO/Ami Vitale

Credit FAO

 

# 9011

 


The case for camels being a likely route of MERS-CoV to humans has become a bit stronger with yesterday’s publication of an EID journal study showing that camels intentionally inoculated with the human MERS strain shed copious amounts of the virus via nasal discharge for at least a week.


This isn’t the first time camels have been implicated as an intermediate host (bats are still eyed as the likely primary reservoir of the MERS virus), but this study does show a plausible route of both camel-to-camel and camel-to-human transmission.

 

Earlier this summer, in mBio: Airborne Fragments Of MERS-CoV Detected In Saudi Camel Barn, we saw some limited evidence that MERS could be an airborne virus.   But other modes of transmission – such as droplet, direct contact, or contaminated fomites – are thought to be bigger factors.

 

Over the past 6 months we’ve seen a steady stream of new information implicating camels as a host for the virus, and a  possible conduit to the human population.

 

FAO: `Stepped Up’ Investigations Into Role Of Camels In MERS-CoV

Mackay’s Compendium Of Camel-MERS Studies

CIDRAP: More Evidence for Camel-to-Human MERS-CoV Transmission

Kuwait Tests Camels - Finds 6% Positive For MERS-CoV

 

A couple of weeks ago, the KSA MOH Reiterated Camel Warnings On MERS, urging breeders and owners to limit their contact with camels, and to use PPEs (masks, gloves, protective clothing) when in close contact with their animals. 

 

Today’s study not only shows that infected camels can shed massive amounts of the MERS coronavirus from their nasal discharges, that they can do so without showing other signs of serious illness.

 

Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels

image
Danielle R. Adney, Neeltje van Doremalen, Vienna R. Brown, Trenton Bushmaker, Dana Scott, Emmie de Wit, Richard A. Bowen1Comments to Author , and Vincent J. Munster1

Author affiliations: Colorado State University, Fort Collins, Colorado, USA; (D.R. Adney, V.R. Brown, R.A. Bowen); National Institutes of Health, Hamilton, Montana, USA (N. van Doremalen, T. Bushmaker, D. Scott, E. de Wit, V.J. Munster) 

Abstract

In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals.

Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.

<SNIP>

This is actually some pretty impressive work, and helps fill in some major gaps in our knowledge of the ecology of the MERS virus among camels.  While based on just three test subjects, no virus shedding was observed in camel urine of feces. 


Possible infection via consumption of camel milk or camel meat was not investigated, and remains an open question (see Eurosurveillance: MERS-CoV Antibodies & RNA In Camel’s Milk – Qatar).

Some excerpts from the discussion follow, but download the entire study for more on methods and materials.

Discussion

(excerpt)

The large quantities of MERS-CoV shed in nasal secretions by each of the 3 camels suggest that camel-to-camel and camel-to-human transmission may occur readily through direct contact and large droplet, or possibly fomite transmission. Histopathologic examination revealed that the URT, specifically the respiratory epithelium in the nasal turbinates, is the predominant site of MERS-CoV replication in camels.

Neutralizing antibodies were detected from 14 dpi onward, reaching a maximum neutralizing titer of 640 after 35 days. Serologic studies in camels in the field have reported MERS-CoV neutralizing titers as high as 5,120 (14,16), potentially indicative of repeated exposure and re-infection.

The study reported here was done on the basis of inoculation of 3 male animals with a human isolate of MERS-CoV, and the study design we used imposed several limitations on how these data inform what occurs in natural infections. The camels we inoculated were exposed to a high dose of virus by 3 simultaneous routes of inoculation.

In retrospect, the inoculation dose does not seem excessive, based on the large quantity of virus shed nasally in all 3 animals (Figure 2). The total dose inoculated was relatively equivalent to the amount of virus present in a single nasal swab sample taken during the first days postinoculation, and it seems probable that a camel shedding this quantity of virus would readily infect other camels or humans with which it had direct contact. The fact that we inoculated the camels with the virus by 3 routes precludes drawing conclusions regarding efficiency of transmission by a particular route, which is a topic that should be addressed in future studies.

The influence of camel age on susceptibility and dynamics of virus shedding is another notable parameter that requires further study. It seems likely that productive infection and shedding of virus in natural settings occurs predominantly in juvenile camels (28). This could be the result of an intrinsic difference in age-related susceptibility, but is more likely related to the immunologically naïve status of the animals in the context of a high force of infection after decay of passively acquired antibodies. The animals we infected were young adults, but were seronegative and therefore probably as susceptible as juveniles from MERS-CoV–endemic regions.

Another aspect of pathogenesis not addressed here is whether virus is present in milk or meat from infected camels and thereby poses another potential route of exposure to humans who consume such products. Despite these limitations, the magnitude and pattern of virus shedding was essentially identical in all 3 animals and supports the available epidemiologic data indicating that camels are likely a major reservoir host for MERS-CoV. Additional experimental and field studies are clearly required to address the duration of shedding of infectious MERS-CoV from infected camels, to determine whether infection results in protective immunity, and to clarify the burden of illness among humans resulting from transmission from camels.

No comments: