To find cases, we interviewed clinicians, reviewed regional records, and searched a national laboratory database. We interviewed all persons who had received a MERS-CoV diagnosis in the region and reviewed hospitalized patients’ medical charts; proxy interviews were conducted for patients who were in the intensive care unit or who had died. We then conducted a retrospective cohort study to assess infection risk factors among household members. We aimed to interview and test all members of the 4 households of the 5 known MERS-CoV–infected patients, as well as relatives who regularly visited these households and were present on the day of the on-site investigation.

On June 5, trained nurses collected 1 oropharyngeal and 1 nasopharyngeal swab for rRT-PCR and 1 blood sample for serologic testing from all available household members and visiting relatives. Hospitalized persons, persons who previously had tested positive by rRT-PCR, and children <14 years of age did not undergo serologic testing. Local public health officials had previously collected oropharyngeal swabs for rRT-PCR in the households during May 20–29; we reviewed these records. On June 5, trained physicians administered a standardized questionnaire to household members and visiting relatives to identify symptoms and healthcare exposures and infection risk factors, including animal contact, recent travel, underlying medical conditions, tobacco use, and details of exposure to each household’s index patient. An index patient was defined as the person with rRT-PCR confirmation of MERS-CoV who had the earliest date of symptom onset in the household.

To understand whether this outbreak was affecting the broader community, we collected data at the town’s hospital, at the outpatient clinic nearest the family’s homes, at 2 local slaughterhouse facilities, and at the town’s weekly livestock animal market. All hospital staff members who had treated the first identified MERS-CoV patient from his admission on May 9 until his MERS-CoV diagnosis on May 20 underwent hospital-based rRT-PCR of oropharyngeal swabs May 21–23; serologic testing was not performed. At the outpatient clinic, all staff and a convenience sample of patients who visited the clinic on June 4 with respiratory symptoms or fever were interviewed with a standardized questionnaire and tested for MERS-CoV by using nasopharyngeal and oropharyngeal swabs for rRT-PCR and blood for serologic testing. All animal workers at 2 local slaughterhouse facilities and a convenience sample of persons with daily animal contact who were present at the town’s weekly livestock animal market on June 4 were interviewed and tested by using the same methods.

Specimens from hospitalized patients and hospital staff members underwent rRT-PCR at the Ministry of Health’s Jeddah regional laboratory, according to Ministry of Health protocol (18). Nasopharyngeal and oropharyngeal flocked swabs collected in the households, at the community clinic, and in animal workers were placed in viral transport media and transferred at 4°C to King Abdulaziz University, where rRT-PCR amplification of consensus viral RNA targets (upstream of E and open reading frame 1a) was undertaken (19). Serum samples were sent to CDC and screened for MERS-CoV antibodies by the recombinant MERS-CoV nucleocapsid protein ELISA, and confirmatory testing was conducted with immunofluorescence assay and microneutralization (20).

We analyzed questionnaire data using Epi Info 7.0 (CDC, Atlanta, GA, USA). Proportions were compared by using the ?2 or Fischer exact test and medians by using Wilcoxon rank-sum. Risk ratios (RRs) were calculated. We compared questionnaire data for all MERS-CoV–positive (by rRT-PCR or serology) relatives >14 years of age with questionnaire data for all MERS-CoV–negative relatives >14 years of age. We excluded children from analysis because they had not had antibody testing of serum. A household secondary transmission analysis comprised relatives >14 years of age residing only in the 4 affected households. Results for MERS-CoV–positive household members who had illness onset (or tested MERS-CoV–positive) at least 2 days after the household’s index patient’s illness onset were compared with results for MERS-CoV–negative household members.

Because this investigation was part of a public health response, it was not considered by CDC and the Saudi Arabia Ministry of Health to be research that was subject to review by an institutional review board. Participants gave verbal consent.

MERS-CoV was diagnosed in 11 (58%) of the 19 patients by rRT-PCR, the standard method in Saudi Arabia (Table 1). For 7 of these, including the 5 original patients, illness was diagnosed during May 20–June 9 while they were hospitalized (Figure 2). For the other 4 patients (L, M, N, and O), MERS-CoV infection was diagnosed during May 22–June 11 through routine contact tracing and rRT-PCR by regional health officers. One of these contacts denied symptoms, 2 reported mild symptoms (i.e., cough, subjective fever) but had not sought medical care, and 1 (N, the only child given a MERS-CoV diagnosis) had visited an emergency department with fever. In the 4 households, all nonhospitalized family members were rRT-PCR–negative when tested on June 5, indicating little risk for ongoing household transmission.

For 8 (42%) of the 19 positive family members, MERS-CoV infection was diagnosed only retrospectively by using serology. All 8 previously had tested negative by rRT-PCR during April 21–May 29 while hospitalized or during routine contact tracing, and all again tested negative on June 5. Two of these rRT-PCR–negative patients (A and B) had extended hospitalizations; 2 patients (G and H) had brief hospitalizations; 2 patients (R and S) had sought medical care but not required hospitalization; and 2 (P and Q) denied symptoms. Some of these patients had multiple negative tests; during an April 2014 hospitalization in Jeddah, patient A, the first patient in this family to become ill, had 3 negative rRT-PCR results of nasopharyngeal swabs.

Among the 19 relatives in whom MERS-CoV infection was diagnosed, 11 (58%) were hospitalized; 3 (16%) were treated in an emergency department for symptoms but not hospitalized; 2 (11%) reported mild symptoms but had not sought medical care; and 3 (16%) were asymptomatic. Five (26%) were intubated, 2 of whom (11%) died while hospitalized. Fever was the most commonly reported symptom (74%), followed by cough (63%), shortness of breath (44%), and diarrhea (44%). The 11 hospitalized patients were ill at home for a median of 3 days before hospital admission (range 0–9 days) (Figure 2).

Fifteen (83%) of 18 MERS-CoV–positive adults were male, compared with 15 (37%) of 41 MERS-CoV–negative adults (p = 0.0009; Table 2). MERS-CoV–positive adults were more likely to have smoked sheesha, the traditional water pipe for flavored tobacco, than were MERS-CoV–negative adults (2/18 [11%] vs. 0/41; p = 0.003) and were more likely to have traveled to Jeddah (10 [56%] vs. 9 [22%]; p = 0.011) and visited a hospital there (7 [39%] vs. 5 [12%]; p = 0.019) during the month before becoming ill. MERS-CoV–positive adults were older (median age 37 years vs. 25 years; p = 0.0011) and more likely to report chronic medical problems (8 [44%] vs. 5 [12%]; p = 0.006), including diabetes mellitus and heart disease. All MERS-CoV–positive relatives denied animal contact during the 14 days before testing.

In household 1, eight of the 12 adults (a husband and wife, 5 of their adult sons, and 1 son’s wife) and 1 of the 7 children received a MERS-CoV diagnosis (household attack rate 44%; household adult attack rate 64%) (Figure 1). In household 2, five of the 12 adults (a husband and wife and 3 of their adult sons) received a MERS-CoV diagnosis (household attack rate 29%; household adult attack rate 42%). In households 3 and 4, only the index patients (both adult men) tested positive; no secondary patients were identified. All family members in whom MERS-CoV symptoms developed or who had positive rRT-PCR results reported contact with at least 1 ill relative in the preceding 14 days (Figure 3).

When we compared results for the 9 secondary adult patients (adults who tested MERS-CoV–positive with illness onset after the presumed index patient) in these 4 households with the results for 21 adults in the households who tested negative, we identified several major risk factors for MERS-CoV transmission in univariate analysis (Table 3). These risk factors included sleeping in the same room as an index patient (RR 4.1, 95% CI 1.5–11.2), touching his respiratory secretions (RR 4.0, 95% CI 1.6–9.8), and removing his biological waste (RR 3.2, 95% CI 1.2–8.4). Notable variables not associated with being a secondary patient included hugging or social kissing; sharing plates, cups, meals, sheesha, or a toilet; and cleaning or feeding the index patient.

Except for members of this extended family, the regional hospital admitted no other MERS-CoV patients. Of 131 hospital workers who cared for patient C, 1 (0.8%), a nurse who remained asymptomatic, tested positive by rRT-PCR on May 23. All 44 persons tested at the outpatient clinic (21 patients with respiratory complaints and 23 staff) were MERS-CoV–negative by both rRT-PCR and serology. All 11 slaughterhouse workers and 10 livestock market participants tested negative by rRT-PCR. One (5%) asymptomatic slaughterhouse worker demonstrated antibodies to MERS-CoV by serology. He had no known contact with any family members in the cluster.