2017 Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Ar

2017·1.03 MB·English

Open Access Research
Case characteristics among Middle East
respiratory syndrome coronavirus
outbreak and non-outbreak cases
in Saudi Arabia from 2012 to 2015
F S Alhamlan,1,2 M S Majumder,3,4 J S Brownstein,4 J Hawkins,4 H M Al-Abdely,5
A Alzahrani,5 D AObaid,1 M N Al-Ahdal,1,2,6 A BinSaeed5
Tocite:AlhamlanFS, ABSTRACT
Strengths and limitations of this study
MajumderMS, Objectives:Asof1November2015,theSaudi
BrownsteinJS,etal.Case
MinistryofHealthhadreported1273casesofMiddle ▪ Confirmed outbreak and non-outbreak cases of
characteristicsamongMiddle
Eastrespiratorysyndrome Eastrespiratorysyndrome(MERS);amongthese Middle East respiratory syndrome (MERS) cor-
coronavirusoutbreakand cases,whichincluded 9outbreaksatseveralhospitals, onavirus infections in Saudi Arabia from
non-outbreakcasesinSaudi 717(56%)patientsrecovered,14(1%)remain September 2012 through October 2015 reported
Arabiafrom2012to2015. hospitalisedand543(43%)died.Thisstudyaimedto to the Saudi Ministry of Health (MOH) were
BMJOpen2017;7:e011865. determinetheepidemiological,demographicand abstractedandanalysed.
doi:10.1136/bmjopen-2016- clinicalcharacteristicsthatdistinguishedcasesof ▪ This is the first report to retrieve the epidemio-
011865 MERScontractedduringoutbreaksfromthose logical, demographic and clinical characteristics
contractedsporadically(ie,non-outbreak)between of MERS data from this database and analyse
▸ Prepublicationhistoryand 2012and2015inSaudiArabia. thesedatausingunivariateanddescriptivestatis-
additionalmaterialis Design:DatafromtheSaudiMinistryofHealthof ticalanalyses.
available.Toviewpleasevisit confirmedoutbreakandnon-outbreakcasesofMERS ▪ However, major leadership changes in the Saudi
thejournal(http://dx.doi.org/ coronavirus(CoV)infectionsfromSeptember2012 MOHduringthestudyperiodledtoalterationsin
10.1136/bmjopen-2016- throughOctober2015wereabstractedandanalysed. the data collection forms as well as the surveil-
011865).
Univariateanddescriptivestatisticalanalyseswere lancesystem.
conducted,andthetimebetweendiseaseonsetand ▪ Thesealterationscausedsomeinconsistenciesin
confirmation,onsetandnotificationandonsetand the data acquired from the Saudi MOH database
Received12March2016
deathwereexamined. that may limit the interpretation of the study
Revised14September2016
Accepted27September2016 Results:Atotalof1250patients(aged0–109years; results.
mean,50.825years)werereportedinfectedwith
MERS-CoV.Approximatelytwo-thirdsofallMERS
caseswerediagnosedinmenforoutbreakandnon- sputum of a man aged 60 years in 2012,1
outbreakcases.Healthcareworkerscomprised22%of 1618 laboratory-confirmed cases of Middle
allMERScasesforoutbreakandnon-outbreakcases. East respiratorysyndrome (MERS) have been
Nosocomialinfectionscomprisedone-thirdofallSaudi reported throughout 26 countries, with 579
MERScases;however,nosocomialinfectionsoccurred cases resulting in death.2 The vast majorityof
morefrequentlyinoutbreakthannon-outbreakcases
these 26 countries reported MERS cases after
(p<0.001).PatientscontractingMERSduringan
experiencing an exportation event from the
outbreakweresignificantlymorelikelytodieofMERS
Arabian Peninsula.3 4 Most casesto date have
(p<0.001).
occurred in Saudi Arabia, followed by South
Conclusions:Todate,nosocomialinfectionshave
Korea, which experienced an outbreak of
fuelledMERSoutbreaks.GiventhattheKingdomof
MERS after the return of an infected busi-
SaudiArabiaisaworldwidereligioustraveldestination,
localisedoutbreaksmayhavemassiveglobal nessman who had been travelling in Middle
implicationsandeffectiveoutbreakpreventive East.5
measuresareneeded. The exact zoonotic source of MERS-CoV
and its mode of transmission in humans
remain unclear. Although related sequences
Fornumberedaffiliationssee
have been detected in several bat species,6
endofarticle.
MERS-CoV has not been isolated from bats.
INTRODUCTION However, MERS-CoV has been isolated from
Correspondenceto
DrFSAlhamlan; Following the isolation of a previously dromedary camels. A high rate of seropositiv-
[email protected] unknown coronavirus (CoV) from the ity has been confirmed in the camels of
AlhamlanFS,etal.BMJOpen2017;7:e011865.doi:10.1136/bmjopen-2016-011865 1
Open Access
ArabianPeninsula, withnoevidence ofMERS-CoVinfec- September 2012 to October 2015 as reported to the
tion detected in cows, goats or sheep.7–10 One study iso- Saudi Arabian Ministryof Health (MOH).
lated the full MERS-CoV genome sequences from a
dromedary camel and from a patient who died of
MATERIALS AND METHODS
laboratory-confirmed MERS-CoV infection after close
Demographic and clinical data were obtained through
contact with camels; the two isolates were identical.
the use of standardised contact tracing forms populated
According to serological data, MERS-CoV had been cir-
by the public health database maintained by the MOH
culating in the camel—but not in the patient—before
Command & Control Center (CCC). According to the
human infection occurred, suggesting that MERS-CoV
CCC, a confirmed MERS-CoV case is defined as a sus-
had been transmitted to the patient via the infected
pected case with laboratory confirmation of MERS-CoV
camel.11
infection. A suspected case of MERS-CoV in adults
Whether MERS-CoV is new to camel or human popu-
(>14years) is defined as follows: (1) acute respiratory
lations or whether it has been present but undetected
illness with clinical or radiological evidence of pneumo-
for years remains unknown. Nonetheless, MERS-CoV was
nia or acute respiratory distress syndrome; (2) a hospita-
initially regarded primarily as a zoonotic pathogen, with
lised patient with healthcare-associated pneumonia
only limited documentation of person-to-person trans-
based on clinical and radiological evidence; (3) upper
mission. However, MERS outbreaks of varying propor-
or lower respiratory tract illness within 2weeks of expos-
tions have since occurred across Saudi Arabia;
ure to aconfirmed or probable case of MERS-CoV infec-
additionally, apparent cases of sustained secondary trans-
tion; or (4) unexplained acute febrile illness (≥38°C)
mission have occurred in family clusters12 13 and health-
presenting with body aches, headache, diarrhoea or
carefacilities.14 15
nausea/vomiting, with or without respiratory symptoms,
Much remains unknown about MERS, including the
and with leucopoenia.
risk factors associated with MERS-CoV transmissions in
outbreak and non-outbreak settings. Here, we aimed to
increase our understanding of the spread and mode of Data and statistical analyses
transmission of MERS-CoV by comparing the epidemio- All data collected were stored and analysed using SAS
logical, demographic and clinical characteristics of out- (V.9.4) software. Univariate and descriptive statistics were
break and non-outbreak MERS-CoV infections from conducted to estimate proportions. Associations between
Figure1 IncidenceofMiddleEastrespiratorysyndromecoronavirusinfections(1250confirmedcases)acrosstheKingdomof
SaudiArabia.
2 AlhamlanFS,etal.BMJOpen2017;7:e011865.doi:10.1136/bmjopen-2016-011865
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age and two variables (gender and death) were assessed
Table1 PatientcharacteristicsinMiddleEastrespiratory
using a χ2 test. χ2 analysis using Yates’ correction was
syndromeinfectioncasesreportedintheKingdomof
performed on the data set to compare case character-
SaudiArabiafrom2012to2015
istics among outbreak and non-outbreak cases.
Distributions of time between onset and confirmation, Demographic
characteristics(n) Frequency Percentage
onset and notification and onset and death (among
patients that died) were also determined for outbreak Ageinyears(1244)
0–10 41 3.30
and non-outbreak cases. All reported p values are two-
tailed and were considered to be statistically significant 11–25 63 8.36
26–39 292 31.83
at p<0.05.
40–109 848 68.17
Gender(1246)
Female 439 35.23
RESULTS
Male 807 64.77
Distribution of confirmed MERS-CoV cases over time in
Occupationalstatus(172)
Saudi Arabia
Employed 22 12.79
The prevalence of MERS-CoV was highest in the Riyadh
Unemployed 40 23.26
region with 46.91% of the total reported cases, followed Retired 31 21.51
by the Jeddah (21%), AlAhsa (5.69%), AlMadinah Private 37 18.02
Almonowarah (4.81%), Eastern (4.73%), AlTaif (4.33%) Other 42 24.42
and Makkah (3.29%) regions. The remaining regions Mainreasonfortesting(1247)
comprised 9.14% of the total reported cases (figure 1). Healthcareworker 249 19.97
More than 31% of all confirmed cases of MERS-CoV in Household 138 11.07
Suspect 860 68.97
Saudi Arabia were reported in April and May 2014. The
Healthcareworker(1244)
highest number of outbreaks was reported to have
Yes 275 22.11
occurred in April and May 2014, the second highest in
No 969 77.89
September 2015 and the third highest in February and
Doesthepatientraisecamels?(205)
March2015.
Yes 29 14.15
No 176 85.85
Demographic characteristics Duringthe14daysbeforethepatientbecamesick,didhe/
During the study period, a total of 1250 patients from 0 shetraveloutsideorinsideSaudiArabia?(205)
to 109years old were reported as infected with Yes 195 95.12
No 10 4.88
MERS-CoV in Saudi Arabia. MERS-CoV was prevalent
Wasthepatienthospitalisedwhenapositiveresultwas
among individuals who were 30years or older; in con-
obtained?(450)
trast, individuals who were 26years or younger exhibited
Yes 413 91.78
very low incidence. The distribution of age for all
No 37 8.22
reported cases was almost normal, with a mean of
Didthepatientvisitanyhealthcarefacilitiesduringthe
50.825years and an SD of 19.494years. MERS-CoV was 14daysbeforeonsetofsymptoms?(245)
more prevalent in men (64.77% of total reported cases) Yes 98 40
than in women. Women had an average age of 48years No 109 44.49
(SD, 19years), with a minimum of zero and maximum Unknown 38 15.51
of 90years. Men had an average age of 52years (SD, Doesthepatientsmoke?(205)
19years), with a minimum of zero and a maximum of Yes 36 17.56
109years (table 1). We found a significant association No 169 82.44
between age and gender (χ2=15.22; p<0.01) and Isthepatientdiabetic?(278)
Yes 220 79.14
between gender and death for patients diagnosed with
No 58 20.86
MERS-CoV(χ2=12.75; p<0.01).
DidthepatientdiebeforeOctober2015?(1250)
Online supplementary table S1 presents the national-
Yes 535 42.80
ities of patients diagnosed with MERS-CoV in Saudi No 715 57.20
Arabia. Most patients were Saudi (66%), followed by
Filipino (10.99%), Indian (3.99%) and Yemeni (3.69%)
nationalities. The prevalence of MERS-CoV infections among men
was comparable for outbreak and non-outbreak cases
Univariate analysis foroutbreak versus non-outbreak (p=0.239; table 2). Similarly, approximately two-thirds of
cases all Saudi MERS diagnoses occurred among Saudi
Univariate analysis revealed that older individuals— nationals foroutbreak and non-outbreak cases (p=0.558;
namely,those older than the mean age of 50.825years— table 2). Healthcare workers comprised 22% of all con-
represented a larger than expected proportion of firmed Saudi MERS cases for outbreak and non-
outbreak than of non-outbreak cases (p<0.001; table 2). outbreak cases (p=0.920; table 2). However, nosocomial
AlhamlanFS,etal.BMJOpen2017;7:e011865.doi:10.1136/bmjopen-2016-011865 3
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infections, which comprised one-third of all confirmed cases, the average time from onset to notification was 5.3
Saudi MERS cases, occurred much more frequently and 9.2days, respectively. Among patients who died, the
among outbreak cases than among non-outbreak cases average time from onset to death was 15.6days for out-
(p<0.001). Patients who became infected during out- break cases and 19.5days for non-outbreak cases. All
breaks were more likely to die of MERS than those three distributions were long-tailed, and non-outbreak
infected during non-outbreak conditions (p<0.001). caseswereskewed further right (figures 2–5).
Of the patients reporting data on camel exposure,
17% of the 123 non-outbreak cases and 10% of the 81
DISCUSSION
outbreak cases indicated that they owned or raised
camels; this differencewas not statisticallysignificant. Using the Saudi MOH CCC public health data set on
MERS cases reported to have occurred from September
2012 to September 2015, we found three factors distin-
Distributions of time between onset and the confirmation, guishing outbreak and non-outbreak cases: (1) patients
notification and death older than the mean age of 51years represented a
The average time from onset to confirmation was larger than expected fraction of outbreak than of non-
6.6days for outbreak cases and 11.9days for non- outbreak cases, (2) nosocomial infections occurred
outbreak cases. For outbreak cases and non-outbreak much more frequently among outbreak cases than
Table2 CharacteristicsofpatientswithconfirmedMiddleEastrespiratorysyndromecoronavirusinfectionintheKingdomof
SaudiArabiafrom2012to2015evaluatedbyoutbreakversusnon-outbreakconditions
Outbreakcases Non-outbreakcases
N=485 N=765
n Percent n Percent χ² pValue
Age(years)
≥51 281 58 362 47 12.66 <0.001
<51 204 42 401 52
Unknown(UNK) 0 2
Sex
Male 323 67 484 63 1.39 0.239
Female 160 33 279 36
UNK 2 2
Nationality
Saudi 331 68 509 67 0.34 0.558
Non-Saudi 153 32 255 33
UNK 1 1
Healthcareworker(HCW)
Yes 108 22 167 22 0.01 0.920
No 375 77 594 77
UNK 2 4
PatienthospitalisedpriortoonsetofMERSsymptoms(nosocomialinfection)
Yes 193 40 220 29 15.84 <0.001
No 292 60 545 71
Reasonfortesting(modeoftransmission)
Suspect 357 74 503 66 22.85 <0.001
HCW 99 20 150 20
Household 27 6 110 14
UNK 2 2
Reasonfortesting(symptomspresented)
Group1 107 22 288 28 100.84 <0.001
Group2 96 20 65 8
Group3 11 2 35 5
Group4 140 29 288 28
Group5 128 26 85 11
Group6 1 0 3 0
UNK 2 1
Outcome
Deceased 245 51 290 38 18.76 <0.001
Alive 240 49 475 6%
Yates’correctionwasusedforallχ2calculations.
4 AlhamlanFS,etal.BMJOpen2017;7:e011865.doi:10.1136/bmjopen-2016-011865
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Figure3 Histogramofthetimefromdiseaseonsetto
MERS-CoVconfirmationforoutbreakandnon-outbreak
cases.Averagetimefromonsettoconfirmationwas6.6days
foroutbreakcasesand11.9daysfornon-outbreakcases.
among non-outbreak cases and (3) patients infected
during outbreaks were more likely to die of MERS-CoV
infection than those infected during non-outbreak con-
ditions (table 2).
Given that age was associated with death, it is worth
noting that the third factor may be explained in part by
the over-representation of older individuals among the
outbreak cases. Although age was also associated with
gender, we found that the proportion of MERS-CoV
infections in men was approximately two-thirds for out-
break and non-outbreak cases (table 2). However, the
general over-representation of men is consistent with
many previous studies showing predominantly male
patients with MERS-CoV.3 16 17
Our results also showed that healthcare workers com-
prised 22% of all Saudi MERS cases diagnosed up to
October 2015 (table 2). This percentage is in agreement
with a 2014 WHO report stating that 109 of the 402
(∼25%) reported MERS-CoV infections in the Jeddah
(Saudi Arabia) 2014 outbreak occurred in healthcare
workers.16 Areas neighbouring Saudi Arabia, including
the city of Al-Ain in the United Arab Emirates, also
reported MERS-CoV infections in 16 healthcare workers
out of 23 total cases.17 Additionally, during the large
Figure2 Epidemiologicalcurveshowingthenumberof Figure4 Histogramoftimefromdiseaseonsetto
casesofMERS-CoVinfectionandvariouspatient notificationforoutbreakandnon-outbreakcases.Average
characteristicsintheKingdomofSaudiArabiabymonthand timefromonsettonotificationwas5.3daysforoutbreak
yearofconfirmation.HCW,healthcareworker. casesand 9.2daysfornon-outbreakcases.
AlhamlanFS,etal.BMJOpen2017;7:e011865.doi:10.1136/bmjopen-2016-011865 5
Open Access
inconsistent over the years during which these data were
acquired, likely due to major leadership changes in the
MOH. The outbreak cases have thus far been confirmed
faster than non-outbreak cases, indicating that improved
future surveillance may allow for faster identification of
sporadic cases (figure 5).
CONCLUSIONS
Although it has been 3years since MERS-CoV was first
identified in humans, cases continue to occur in house-
hold and healthcare settings, though our results indi-
Figure5 Histogramoftimefromonsettodeathforoutbreak cated that most person-to-person transmissions involved
andnon-outbreakinthosecasesendingindeath.Average healthcare-associated infections. Nosocomial outbreaks
timefromonsettodeathamongpatientswhodiedwas likely begin when a primary patient seeks care and then
15.6daysforoutbreakcasesand19.5daysfornon-outbreak escalates due to insufficient implementation of scalable
cases.
infection control measures. Our results indicate that the
best way to control MERS-CoV infections may be to
South Korean outbreak in 2015, 14% of the infected block its spread by practicing rigorous infection control
caseswerein healthcareworkers.5 measures in hospitals. Therefore, strengthening of infec-
Another 2014 WHO report stated that most tion control measures in healthcare settings will be crit-
person-to-person MERS-CoV infections likely occurred ical tothe prevention of futureoutbreaks.
inhealthcaresettings.18 Wefound that nosocomial trans-
missions comprised one-third of all Saudi MERS-CoV Authoraffiliations
cases reported to date. Importantly, these nosocomial 1DepartmentofInfectionandImmunity,KingFaisalSpecialistHospitaland
infections occurred more frequently in outbreak cases ResearchCenter,Riyadh,SaudiArabia
2CollegeofMedicine,AlfaisalUniversity,Riyadh,SaudiArabia
than in non-outbreak cases, suggesting that nosocomial
3MassachusettsInstituteofTechnology,Cambridge,Massachusetts,USA
infections fuelled outbreaks (table 2). The first outbreak 4BostonChildren’sHospital,Boston,Massachusetts,USA
in Al-Hasa, Saudi Arabia, (2013) provided valuable infor- 5PublicHealthDeputy,MinistryofHealth,Riyadh,SaudiArabia
mation about MERS-CoV transmission in a healthcare 6DepartmentofPathologyandLaboratoryMedicine,KingFaisalSpecialist
setting. The outbreak started in a haemodialysis unit of HospitalandResearchCenter,Riyadh,SaudiArabia
a private hospital in Al-Hasa, but subsequently spread to
Twitter FollowDaliaObeid@obeiddx92
three other hospitals. Phylogenetic analysis of the out-
break showed that only eight of the epidemiological
Acknowledgements TheauthorsaregratefultotheMinistryofHealthstaff
transmissions were related, indicating multiple zoonotic whohelpedindatacollection.
introductions of MERS-CoV.18
Contributors FSAisthestudyPIandwrotethemanuscript.MSMdeveloped
To date, MERS-CoV has been detected in camels from
thestudydesignandconductedtheanalyses.JHinterpretedtheresults.JSB
Saudi Arabia, Oman, Qatar, Jordan and Kenya,7 8 10 19 20 reviewedthestudydesign.DAOperformedthestatisticalanalyses.HMA-A,AA
and it has been shown that humans can acquire andABSacquiredpatientdemographicandclinicaldatafromtheSaudi
MERS-CoV directly from dromedary camels.21 Since MinistryofHealthdatabase.MNA-Aparticipatedininterpretingtheclinical
resultsandreviewedthemanuscript.Allauthorsparticipatedincritical
camel exposure data (ie, whether the patient owned or
revisionofthemanuscriptandapprovedthefinalversion.
raised camels) were gathered for only 204 of the 1250
Funding ThisstudywaspartiallysupportedbyasummergrantfromKing
cases in the database used by this study, we did not
AbdulazizCityforScienceandTechnology(15/3171).
include this information in table 2. Nonetheless, we
found that 17% of the 123 non-outbreak cases and 10% Competinginterests Nonedeclared.
of the 81 outbreak cases reporting data on camel expos- Ethicalapproval ThisstudywasapprovedbytheOfficeofResearchAffairs
ure indicated that the patients owned or raised camels. ofKingFaisalSpecialistHospitalandResearchCentre(KFSH&RC;RAC#2130
Although this difference was not statistically significant, 033)andtheMinistryofHealthinRiyadh,SaudiArabia,andincludeda
waiverofinformedconsent.Informedconsentwaswaivedbecausethisstudy
this result suggested that camel exposure, and thus zoo-
involvedaretrospectiveevaluationofpubliclyavailabledata,thedata
notic transmission, might be more common among collectionwasanonymousandnopatientidentitywasrevealed.
sporadic, non-outbreak cases than among outbreak
Provenanceandpeerreview Notcommissioned;externallypeerreviewed.
cases. A full analysis of this relationship will require
Datasharingstatement Noadditionaldataareavailable.
morevigilant collection of camel exposure data.
This study was limited by the information available in OpenAccess ThisisanOpenAccessarticledistributedinaccordancewith
the Saudi MOH CCC public health data set on theCreativeCommonsAttributionNonCommercial(CCBY-NC4.0)license,
whichpermitsotherstodistribute,remix,adapt,builduponthisworknon-
MERS-CoV infections that were reported to have
commercially,andlicensetheirderivativeworksondifferentterms,provided
occurred between September 2012 and October 2015.
theoriginalworkisproperlycitedandtheuseisnon-commercial.See:http://
The surveillance system and data collection forms were creativecommons.org/licenses/by-nc/4.0/
6 AlhamlanFS,etal.BMJOpen2017;7:e011865.doi:10.1136/bmjopen-2016-011865
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