Concerns about Misinterpretation of Recent Scientific Data Implicating Dromedary Camels in Epidemiology of Middle East Respiratory Syndrome (MERS)

This letter addresses some concerns about two recent articles published by the same authors in mBio (1, 2), specifically many uncertainties regarding the potential applicability of their epidemiological data, which were obtained from dromedary camels (DCs) infected with Middle East respiratory syndrome coronavirus (MERS-CoV), to human public health. Aiming to investigate the possible role of DCs in the transmission of MERS-CoV to humans, the authors in their first article determined the seroprevalence of MERS-CoV infection in DCs throughout Saudi Arabia and arrived at three main conclusions (1). Their first conclusion was that DCs can be infected with MERS-CoV, as evident by the determination of (i) high loads of viral nucleic acids (RNA) and antibodies to MERS-CoV in archived and freshly collected samples and (ii) a high resemblance ( 99%) in the collected samples in three regions of phylogenetically analyzed MERS-CoV genomic sequence. Their second conclusion is that there are seroprevalence differences in MERS-CoV infection depending on the camel’s age (95% of the adults compared to 35% of the juveniles) and the region of the country (ranging from 90% in the East to 5% in the Southwest). The third conclusion is that airborne transmission is the main mode of MERS-CoV transmission, as evidenced by the more frequent detection of viral nucleic acids in nasal swabs than in rectal specimens. Furthermore, the authors in their second article described complete genomic sequencing of MERS-CoV isolated from both DCs and humans and arrived at two more conclusions (2). First, they demonstrated that DCs can be simultaneously infected with three genetic variants (genotypes) of MERS-CoV; second, they showed that the alignment of the complete genomic sequence of one MERS-CoV genotype (claimed to be a quasispecies) obtained from culturing the virus from nasal swab samples of DCs was indistinguishable from the genomic sequence of MERS-CoV recovered from humans. Based on all these findings, the authors speculated that DCs may have a role or serve as a potential reservoir or vector of MERS-CoV in human infection and they clearly argued that we ought to orient future investigations on MERS disease among humans toward direct or indirect exposure to DCs. Although these findings are remarkable and obviously advance our knowledge in pursuing the evolutionary emergence of MERS disease, we argue that they cannot be taken as conclusive evidence in implicating DCs as harboring the infectious form of MERSCoV and as serving as the source of infection for humans; much less, these findings are still only speculations and their utmost scientific importance is the assumption of an emerging interspecies transmission of MERS-CoV. In fact, our concerns can be better understood when discussed in the context of emergence (and reemergence) of infectious diseases, factors which were largely ignored by the authors over the mechanism of MERS-CoV emergence between humans and DCs and the most relevant to the debate. To elucidate this issue, four possible routes of MERS-CoV transmission should be epidemiologically assessed: human to human, camel to camel, camel to human, and human to camel. Regarding human-to-human MERS-CoV transmission, clusters of infection cases have indicated that MERS-CoV actually can be spread horizontally from human to human through close contact (3–5). Effective and successful emergence of MERS-CoV requires that the value of the basic reproduction number (R0) should exceed 1 in the new host (presumably human) (6). In the case of MERS, the R0 is currently less than 1 (most likely 0.5), indicating that MERS-CoV infection will inevitably die out; however, it is recommended, in such cases, to take into account the demographic stochasticity of MERS-CoV transmission (7). Despite the limited human-to-human transmission, the recent increases in the number of MERS-CoV infections among humans and the exceptionally high fatality rate associated with it as reported by WHO (8) represent a marked increase in MERS emergence (i.e., an increase in R0) and subsequently an epidemic waiting to happen, which obviously is the key driver in the current debate. Regarding camel-to-camel transmission, although the identification of antibodies and viral nucleic acids of MERS-CoV in DCs is remarkable, these findings suggest only that DCs can be naturally infected with MERS-CoV and provide us with no clues as to how this transmission occurs. We recognize that these findings, together with the absence of viremia, as reported by the authors, and the lack of even a single case fatality in DCs, indicate that DCs may not only be a useful animal model for evaluating candidate vaccines and drugs against MERS but also a good reservoir of MERS-CoV. However, this form of transmission cannot yet be ascertained to implicate DCs as a significant reservoir species in the epidemiology of MERS-CoV, as noted by Nishiura et al. (9). These authors stated that two conditions should be objectively examined to confirm that an animal species constitutes a reservoir: (i) the reservoir is sufficient to maintain the disease by frequently transmitting the virus to another host, and (ii) the presence of the reservoir is essential for the continuous transmission of infection. The results presented by Lipkin and colleagues in mBio