High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014

Farag, Elmoubasher A. B. A.; Reusken, Chantal B. E. M.; Haagmans, Bart L.; Mohran, Khaled A.; Raj, V. Stalin; Pas, Suzan D.; Voermans, Jolanda; Smits, Saskia L.; Godeke, Gert-Jan; Al-Hajri, Mohd. M.; Alhajri, Farhoud H.; Al-Romaihi, Hamad E.; Ghobashy, Hazem; El-Maghraby, Mamdouh M.; El-Sayed, Ahmed M.; Al Thani, Mohamed H. J.; Al-Marri, Salih; Koopmans, Marion P. G.

Antibodies to MERS-CoV S1 were found in 100 out of 103 animals tested by micro-array technology (9) . For 53 animals, antibody levels were also determined by virus neutralization assay as described earlier (9) . Almost all animals had detectable neutralizing antibodies with no obvious age pattern and no significant difference in proportion of animals with low antibody levels ( B20) (Fig. 2a) . There was no correlation between antibody levels and the viral load as reflected by Ct values (Fig. 2b) . (10) A study at four slaughterhouses in Egypt showed an overall RNA prevalence in nasal swabs of 3.6% among 110 camels (11) , which is significantly lower than in our study. A comparison of the organization of the meat markets between Egypt and Qatar could provide insight in the observed differences. The camels that are put together for a holding period of weeks prior to slaughter in Doha have a wide variety of origins with varying initial immune status, which might provide a platform for extensive virus circulation. These include naïve camels from Australia (12) and camels from areas in the Horn of Africa and the Gulf region with known differences in immune status (2, 13, 14) . We observed a positivity rate in rectal swabs of 15 out of 103 animals that were analyzed (of which 61 were positive in nasal swabs). Other studies observed none to very low numbers of camels shedding MERS-CoV RNA in feces (3, 15) . However, the total numbers of animals in these studies were too low to make a significant comparison with the data presented here. In the current views on MERS-CoV epidemiology, young camels ( 51year) with primary infections are thought to play a bigger role in MERS-CoV transmission than older animals for which less frequent shedding is observed (4, 15) and who demonstrate higher rates of seroconversion reviewed in (Ref. 2) . However, we observed no significant differences in MERS-CoV RNA shedding between different age groups. Moreover, the lack of correlation between viral RNA loads and levels of neutralizing antibodies in the animals suggests limited protection and potential for reinfection despite previous exposure, similar to the situation in humans with the four common human CoVs and as observed in a camel herd in KSA (15) . A problem is that the time since onset of infection could not be determined as the animals did not show overt symptoms. Therefore, it remains to be determined how the kinetics of infection are. In theory, the observed shedding of virus in the presence of neutralizing antibodies could represent sampling toward the end of an infection cycle. Alternatively, the data may reflect limited mucosal immunity as has been shown for other animal coronaviruses (16) . The possibility of camel vaccination has been suggested as a possible approach to controlling MERS-CoV transmission to humans. However, this may prove to be a challenging task in light of the above observations. Given the high numbers of animals shedding these viruses in dynamic environments like the Doha market and abattoir, potential human health risks need to be considered and the implementation of management alternatives (e.g. separation of naïve animals from previously exposed animals and personal protective equipment for employees) might reduce the burden of MERS-CoV exposure to humans.