Follow-up of Contacts of Middle East Respiratory Syndrome Coronavirus–Infected Returning Travelers, the Netherlands, 2014

Notification of 2 imported cases of infection with Middle East respiratory syndrome coronavirus in the Netherlands triggered comprehensive monitoring of contacts. Observed low rates of virus transmission and the psychological effect of contact monitoring indicate that thoughtful assessment of close contacts is prudent and must be guided by clinical and epidemiologic risk factors.


DISPATCHES
15-0560-Techapp1.pdf). Throat swab samples from 1 relative contact were unavailable; a second serum sample was missing from 7 relatives, 3 aircraft contacts, and 1 travel contact (a woman who had had no contact with animals, had not visited a hospital, and had no concurrent conditions). Eight contacts who reported symptoms (7 unprotected and 1 protected) were sampled immediately after onset of symptoms. MERS-CoV reverse transcription PCR (RT-PCR) was performed on paired throat swabs from 106 (81%) and serologic analysis on paired serum samples from 99 (76%) of the 131 contacts (Table 1). PCR did not detect MERS-CoV RNA from any throat swab or serum samples, and MERS-CoV-specific IgG responses were absent in serum samples tested (8) ( Table 1). All specimens obtained from the symptomatic contacts tested negative by RT-PCR and analysis of paired serum samples for MERS-CoV.
All contacts also received an online questionnaire containing questions about demographics, type of contact, quality of information received, perceived severity and vulnerability, feelings of anxiety, interference of the measures with daily life, and knowledge of the measures and travel advice (online Technical Appendix). To evaluate the effect of monitoring, we used the Revised Impact of Event Scale (IES-R), a validated questionnaire designed to assess current subjective distress for a specific traumatic life event (9). The IES-R contains 22 items divided into 3 subscales: avoidance (e.g., avoidance of feelings), intrusion (e.g., nightmares) and hyperarousal (e.g., anger). The mean score on 3 subscale domains indicates the level of distress experienced (9). Mean scores of unprotected contacts were compared with those of protected contacts by a Wilcoxon rank-sum test or t-test. Significance was determined at the 5% level (p value <0.05). A total subjective stress IES-R score with a maximum score of 88 (Likert scale of 0-4 [0, never; 1, seldom; 2, sometimes; 3, often; 4, very often]) can be calculated. We considered a score >20 to be an indicator of posttraumatic stress disorder to enable comparison with previous studies (10,11).

Conclusions
We monitored 131 contacts of 2 case-patients with imported MERS-CoV infections in the Netherlands. Laboratory testing did not indicate transmission of the virus, including among contacts with high-risk exposures or those who developed respiratory symptoms. We also found no infections among travelers from the same group. Our findings agree with reports from Greece and Italy, in which no and limited secondary transmission, respectively, was found among close contacts of MERS-CoV patients (12,13).
Survey results show a substantial psychological effect of monitoring on contacts, especially unprotected contacts. As with other emerging infections, such as Marburg hemorrhagic fever and severe acute respiratory syndrome, quarantine or monitoring of contacts leads to psychological  distress, measured by high IES-R scores (10,11,14). When stratifying by type of contact, the total mean IES-R score and the subscale scores were highest for unprotected contacts-those with the highest risk for exposure. We found increased symptoms of posttraumatic stress disorder in a considerable number of contacts, similar to findings by Hawryluck et al. (11) and Reynolds et al. (10). The survey response rate of 55% limits interpretation of results; motives for noncompliance remain unknown. Also, recall bias might influence recollection of experiences. Besides exposure, monitoring has contributed to the psychological effect. Whether the number of questions induced stress is not known, but participants did not mention this as a concern.
Our findings illustrate the feasibility of comprehensive follow-up of contacts of MERS-CoV patients and clarify the risk for asymptomatic secondary transmission. The psychological effect of contact monitoring and the observed low rates of MERS-CoV transmission in several studies, including this investigation, indicate that thoughtful but limited assessment of close contacts is prudent. Identification of close contacts of those who are infected should be carefully considered, and decisions about monitoring and testing of contacts should be made primarily on the basis of clinical and epidemiologic risk factors.  Serum samples were tested in at a 1:20 dilution for IgG reactive with MERS-CoV (residues 1-747), severe acute respiratory syndrome-CoV (residues 1-676) and human coronavirus OC43 (residues 1-760) spike domain S1 antigens by using extensively validated protein-microarray technology, as described (3,5). Confirmation was performed by using a neutralization assay (4). based on an integrated model designed to explain health behavior (11,12). Knowledge of MERS-CoV was examined with 7 true/false/don't know statements. The members of the travel group (n = 29) were also asked to answer questions regarding the travel advice they had received before their trip to Saudi Arabia. The presence of concurrent conditions and use of medicines were not part of this questionnaire, but were addressed in another study and published elsewhere (13). The questionnaire took 15 min to fill out and the information was processed anonymously.

Data Analysis
Differences in knowledge, impact of monitoring measures, quality of information, and perception between unprotected and protected contacts were compared in contingency tables by using the  2 test. For assessing knowledge, a summary score was created on the basis of the number of correct answers (range 0-7). Significance was determined at the 5% level (p-≤0.05). Data analysis was performed with SAS 9.3(SAS Institute, Cary, NC, USA).

Demographics
Of the 131 contacts, 72 (55%) filled out the questionnaire. Among the unprotected contacts, the response rate was highest for the travel group (22 [76%] of 29), compared with 19 (59%) of 32 for the other unprotected contacts and 7 (41%) of 17 for the aircraft contacts.
Among the protected contacts the response rate was 24 (45%) of 53. The median age of respondents was 39 years (range 9-77 years), 53% were female, and 51% had at least a college education. Protected contacts were younger (median of 31 years vs. 48 years) and had more education (88% bvs. 31%) than unprotected contacts.

Knowledge of MERS-CoV
Most (83%) contacts were aware of the symptoms related to MERS-CoV infection and knew that MERS-CoV is not common in the Netherlands (83%) (
In becoming infected (35%, n = 25). There were no protected contacts who felt seriously limited in their social contacts because of the measurements they had to take, compared with 16 unprotected contacts (22%) who did feel limited.

Information on MERS-CoV
Written instructions with detailed information on the monitoring measures and their rationale were received by 53 (74%) of 72 respondents. Of these 53 respondents, 41 (77%) found the information to be clear, 33 (73%) complete, 30 (56%) unequivocal. Only 4 (8%) thought the information was confusing, and 2 (4%) thought it was redundant. In total, 25 (47%) thought the information was clear, complete, and unequivocal.

Travel Advice
Twenty-three of the 29 participants to the pilgrimage trip to Saudi Arabia filled out this part of the questionnaire; 21 (91%) received travel advice or vaccinations before the trip (the other 2 were already vaccinated, for example against meningococcal disease and DTP, because of previous traveling). During the pretravel consultation, only 1 person received information on the possible transmission of MERS-CoV in the Middle East (avoid contact with animals, avoid drinking unpasteurized milk, and when having symptoms contact a doctor when returning to the Netherlands). However, although most did not receive any advice, 8 persons watched their health more carefully (35%), 9 reported that they were more compliant with personal hygiene measures during the trip (39%), 3 avoided contact with animals (13%), and 3 avoided contact with animals' waste (13%). Twelve did not change their behavior after receiving travel advice (52%).