MERS-COV (77): SAUDI ARABIA, CAMELS, HUMAN, EPIDEMIOLOGY, ASSESSMENT

Posted on 23RD DEC 2017
tagged MERS-CoV, Saudi Arabia

A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org

Date: Fri 22 Dec 2017
Source: BioRxiv journal [edited]
https://www.biorxiv.org/content/early/2017/08/10/173211

Ref: Dudas G, Carvalho LM, Rambaut A et al. MERS-CoV spillover at the camel-human interface. bioRxiv preprint first posted online 10 Aug 2017; doi: http://dx.doi.org/10.1101/173211.

Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from camels causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, and while case-based and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential. Here we use existing MERS-CoV sequence data to explore its phylodynamics in 2 of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[From the discussion chapter in the paper, the section "MERS-CoV epidemiology" is herewith presented (figures and references, deleted; are to be found in the source URL):

"In this study we aimed to understand the drivers of MERS coronavirus transmission in humans and what role the camel reservoir plays in perpetuating the epidemic in the Arabian peninsula by using sequence data collected from both hosts (174 from humans and 100 from camels). We showed that currently existing models of population structure can identify distinct demographic modes in MERS-CoV genomic data, where viruses continuously circulating in camels repeatedly jump into humans and cause small outbreaks doomed to extinction. This inference succeeds under different choices of priors for unknown demographic parameters and in the presence of strong biases in sequence sampling schemes. When rapid coalescence in the human deme is not allowed structured coalescent inference loses power and ancestral state reconstruction is nearly identical to that of discrete trait analysis. When allowed different deme-specific population sizes, the structured coalescent model succeeds because a large proportion of human sequences fall into tightly connected clusters, which informs a low estimate for the population size of the human deme. This in turn informs the inferred state of long ancestral branches in the phylogeny, i.e. because these long branches are not immediately coalescing, they are most likely in camels.

"From sequence data we identify at least 50 zoonotic introductions of MERS-CoV into humans from the reservoir, from which we extrapolate that hundreds more such introductions must have taken place. Although we recover migration rates from our model, these only pertain to sequences and in no way reflect the epidemiologically relevant per capita rates of zoonotic spillover events.

"We also looked at potential seasonality in MERS-CoV spillover into humans. Our analyses indicated a period of 3 months where the odds of a sequenced spillover event are increased, with timing consistent with an enzootic amongst camel calves. As a result of our identification of large and asymmetric flow of viral lineages into humans we also find that the basic reproduction number [R0] for MERS-CoV in humans is well below the epidemic threshold. Having said that, there are highly customisable coalescent methods available that extend the methods used here to accommodate time varying migration rates and population sizes, integrate alternative sources of information and fit to stochastic nonlinear models, which would be more appropriate for MERS-CoV.

"Some distinct aspects of MERS-CoV epidemiology could not be captured in our methodology, such as hospital outbreaks where R0 is expected to be consistently closer to 1.0 compared to community transmission of MERS-CoV. Outside of coalescent-based models there are population structure models that explicitly relate epidemiological parameters to the branching process observed in sequence data, but often rely on specifying numerous informative priors and can suffer from MCMC convergence issues.

"Strong population structure in viruses often arises through limited gene flow, either due to geography, ecology, or evolutionary forces. On a smaller scale population structure can unveil important details about transmission patterns, such as identifying reservoirs and understanding spillover trends and risk, much as we have done here. When properly understood, naturally arising barriers to gene flow can be exploited for more efficient disease control and prevention, as well as risk management".

Subscribers may find also the section on seasonality of interest (edited):

"We identify 4 months (April, May, June, July) when the odds of MERS-CoV introductions are increased and 4 when the odds are decreased (August, September, November, December). Camel calving is reported to occur from October to February, with rapidly declining maternal antibody levels in calves within the 1st weeks after birth. It is possible that MERS-CoV sweeps through each new camel generation once critical mass of susceptibles is reached, leading to a sharp rise in prevalence of the virus in camels and resulting in increased force of infection into the human population. Strong influx of susceptibles and subsequent sweeping outbreaks in camels may explain evidence of widespread exposure to MERS-CoV in camels from seroepidemiology.

"Although we found evidence of seasonality in zoonotic spillover timing, no such relationship exists for sizes of human sequence clusters. This is entirely expected, since little seasonality in human behaviour that could facilitate MERS-CoV transmission is expected following an introduction. Similarly, we do not observe any trend in human sequence cluster sizes over time, suggesting that MERS-CoV outbreaks in humans are neither growing nor shrinking in size. This is not surprising either, since MERS-CoV is a camel virus that has, to date, experienced little-to-no selective pressure to improve transmissibility between humans".

Between October 2013 and October 2017, MERS-CoV in camels was reported to the OIE from Saudi Arabia (14), Qatar (3), Iran (3), Kuwait (2), Jordan (2), Oman (1) and UAE (1); in October 2012 it was identified in a bat in Saudi Arabia. It was detected also in milk samples in Qatar.

One of the issues yet to be visited, is the striking difference between the human MERS-CoV morbidity rate in Saudi Arabia, compared to all other countries. According to WHO recent (Wed 20 Dec 2017) monthly update, addressing MERS-CoV in humans and animals, the globally accumulated number of human MERS cases totalled 2124, of which 1753 in Saudi Arabia. The update is available at http://www.fao.org/ag/againfo/programmes/en/empres/mers/situation_update....

Figure 2 in the above monthly update presents "Percentage of human MERS-CoV reported cases by source of infection and year". It shows that during the period July 2017 - to date, 34.57 percent of the human cases were "primary with animal exposure", while 37.04 percent were "primary with NO animal exposure" (the remaining cases, 24.69 and 3.70 percent, respectively, stand for "secondary cases" and "no data available). The figure's included comment says: "while infection control improves in healthcare settings and history of animal contact is recorded more consistently in case investigations, the overall number of cases has decreased. The apparent increase in proportion of primary cases with animal exposure therefore should be interpreted in the overall context of a reduced human case count". See at http://www.fao.org/ag/againfo/programmes/en/empres/mers/img/fig2_2017_12....

A map of (Saudi Arabia): http://healthmap.org/promed/p/131. - Mod.AS]

See Also

MERS-CoV (76): Saudi Arabia (MK) WHO 20171222.5518476
MERS-CoV (75): Saudi Arabia (RI, JF, QS) 20171211.5496478
MERS-CoV (68): Israel, animal reservoir, camels, serology, surveillance 20171105.5425773
MERS-CoV (66): Burkina Faso, animal reservoir, camels, FAO, RFI 20171029.5411777
MERS-CoV (64): Saudi Arabia, animal reservoir, human, camel milk 20171012.5375933
MERS-CoV (62): animal reservoir, camels, FAO, OIE, WHO 20171002.5354608
MERS-CoV (40): animal reservoir, camels, review, FAO 20170619.5115999
MERS-CoV (29): Qatar, animal reservoir, camels 20170527.5066519
MERS-CoV (28): Qatar, Saudi Arabia (HA) 20170524.5059234
MERS-CoV (23): Saudi Arabia (AS) animal reservoir, human contact, OIE, RFI 20170421.4986081
MERS-CoV (21): Egypt, animal reservoir, camel, ex Sudan, control, RFI 20170405.4948727
MERS-CoV (18): Africa, animal reservoir, camels, 2015, research 20170331.4939980
2016
----
MERS-CoV (87): Jordan, animal reservoir, camelids, OIE 20160802.4385317
MERS-CoV (66): Saudi Arabia, animal reservoir, camelids, OIE, RFI 20160618.4294807
MERS-CoV (59): animal reservoir, review 20160610.4275921
MERS-CoV (40): Egypt, animal reservoir, camel, ex Sudan, susp. 20160316.4097730
MERS CoV (21): Saudi Arabia, animal reservoir, camel, comment 20160216.4023772
MERS CoV (19): Saudi Arabia, animal reservoir, camel, prevention, RFI 20160204.3995194
MERS-CoV (18): Saudi Arabia, animal reservoir, camel, vaccination, comment 20160203.3990284
MERS-CoV (16): Saudi Arabia (MK) animal reservoir, OIE, RFI 20160201.3985175
MERS-CoV (11): Saudi Arabia, animal reservoir, camel, vaccination, comment 20160126.3966528
MERS-CoV (09): Saudi Arabia, animal reservoir, camel, vaccination considered 20160125.3963370
2015
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MERS-CoV (163): Saudi Arabia, animal reservoir, camel, research, vaccine 20151219.3873486
MERS-CoV (155): animal reservoir, camel, research, RFI 20151110.3781744
MERS-CoV (154): Saudi Arabia, animal reservoir, camel, case control 20151105.3768115
MERS-CoV (143): Kenya, animal reservoir, camel, serosurveillance 20151017.3722887
MERS-CoV (141): Saudi Arabia, animal reservoir, camel debated, RFI 20151016.3720479
MERS-CoV (131): Saudi Arabia, animal reservoir, camels, Hajj, RFI 20150914.3643612
MERS-CoV (130): Saudi Arabia, animal reservoir, camels, Hajj 20150912.3641457
MERS-CoV (114): Saudi Arabia, animal reservoir, camels, Hajj 20150823.3597358
MERS-CoV (104): Saudi Arabia, animal reservoir, camel debate 20150810.3569207
MERS-CoV (63): animal reservoir, bat 20150612.3432410
MERS-CoV (48): UAE (Dubai) animal reservoir, camel 20150527.3386738
MERS-CoV (29): UAE (Dubai) animal reservoir, camel 20150303.3204214
MERS-CoV (27): Saudi Arabia, animal reservoir, camel 20150302.3200502
MERS-CoV (12): animal reservoir, camels debated, case-control study, RFI 20150122.3109335
MERS-CoV (09): Saudi Arabia, animal reservoir, camels debated 20150117.3098294
2014
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MERS-CoV (67): Iran (SB) animal reservoir, camel, ex Pakistan, RFI 20141219.3039497
MERS-CoV (49): Iran (SB), animal reservoir, camel conf, OIE 20141029.2912385
MERS-CoV (46): animal reservoir, camel, S.Arabia, vaccination, Iran susp, RFI 20141027.2904032
MERS-CoV (40): animal reservoir, camel, milk susp, RFI 20141022.2889778
MERS-CoV (24): animal reservoir, camel, experimental infection 20140929.2813981
MERS-CoV (09): animal reservoir, update, OIE, WHO 20140818.2700879
MERS-CoV (07): animal reservoir, camel, bat 20140720.2623848
MERS-CoV - Eastern Mediterranean (79): Qatar (OIE) Kuwait (susp) animal res, RFI 20140611.2533756
MERS-CoV - Eastern Mediterranean (77): S Arabia, Qatar, animal res, control, RFI 20140607.2525113
MERS-CoV - Eastern Mediterranean (75): Animal res, camel, zoonotic aspects 20140604.2518134
MERS-CoV - Eastern Mediterranean (66): Oman (SH), camel conf, OIE 20140523.2493556
MERS-CoV - Eastern Mediterranean (62): Saudi Arabia, Africa, animal res., camel 20140517.2478989
MERS-CoV - Eastern Mediterranean (46): Saudi Arabia, animal reservoir, camel 20140430.2440228
MERS-CoV - Eastern Mediterranean (41): Oman, animal reservoir, camel 20140426.2432011
MERS-CoV - Eastern Mediterranean (39): Qatar (RY) animal res., camel, OIE 20140424.2426491
MERS-CoV - Eastern Mediterranean (34): animal reservoir, camel, Saudi Arabia, RFI 20140419.2414479
MERS-CoV - Eastern Mediterranean (19): Saudi Arabia, UAE, WHO 20140325.2356854
MERS-CoV - Eastern Mediterranean (10): camel, Sudan, Ethiopia 20140228.2307254
MERS-CoV - Eastern Mediterranean (09): animal reservoir, camel, Saudi Arabia 20140227.2303420
MERS-CoV - Eastern Mediterranean (02): animal reservoir, camel, UAE, serology 20140104.2151807
2013
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MERS-CoV - Eastern Mediterranean (106): animal reservoir, camel, Qatar, OIE 20131231.2145606
MERS-CoV - Eastern Mediterranean (101): animal reservoir, camel, goat 20131217.2120936
MERS-CoV - Eastern Mediterranean (98): animal reserv/camel, Jordan, Saudi Arabia 20131213.2114362
MERS-CoV - Eastern Mediterranean (95): animal reservoir, camel, Qatar 20131129.2082942
MERS-CoV - Eastern Mediterranean (94): UAE (Abu Dhabi), Qatar 20131129.2082330
MERS-CoV - Eastern Mediterranean (93): animal res., camel conf, Qatar (RY) OIE 20131129.2082115
MERS-CoV - Eastern Mediterranean (87): animal res. camel susp. precautions 20131113.2053932
MERS-CoV - Eastern Mediterranean (85): animal reservoir, camel, susp, official 20131112.2051424
MERS-CoV - Eastern Mediterranean (83): animal reservoir, camel, susp, RFI 20131112.2050868
MERS-CoV - Eastern Mediterranean (75): role of bats in emergence, Saudi Arabia new cases 20131011.1996687
MERS-CoV - Eastern Mediterranean (68): animal reservoir, camel, research 20130907.1929762
MERS-CoV - Eastern Mediterranean (66): animal reservoir, discussion 20130904.1922998
MERS-CoV - Eastern Mediterranean (61): animal reservoir, bat, comment 20130828.1907567
MERS-CoV - Eastern Mediterranean (57): animal reservoir, bats 20130822.1895035
MERS-CoV - Eastern Mediterranean (53): animal reservoir, serology, FAO 20130811.1875301
MERS-CoV - Eastern Mediterranean (52): animal reservoir, research, serology 20130809.1872008
MERS-CoV - Eastern Mediterranean (50): animal reservoir, OIE 20130727.1849047
MERS-CoV - Eastern Mediterranean (48): animal reservoir, bat susp 20130725.1844412
MERS-CoV - Eastern Mediterranean (39): animal reservoir, research 20130706.1810714
MERS-CoV - Eastern Mediterranean (25): Saudi Arabia, genome 20130612.1768944
MERS-CoV - Eastern Mediterranean (10): animal reservoir, research 20130524.1735984
MERS-CoV - Eastern Mediterranean (03): animal reservoir, RFI 20130519.1723544
MERS-CoV - Eastern Mediterranean (02): WHO summary, ECDC risk assessments 20130518.1721873
Novel coronavirus - Eastern Mediterranean (15): camel exposure 20130405.1623188
Novel coronavirus - Eastern Mediterranean: bat reservoir 20130122.1508656
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