Imported Monkeypox, Singapore

In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally.

In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally.
but negative for variola virus on the BioFire FilmArray Biothreat Panel version 2.5 (https://www.biofiredx.com). We confirmed orthopoxvirus from swab specimen using a panorthopoxvirus PCR targeting E9L (DNA polymerase) (6) and by direct visualization of virus particles using transmission electron microscopy, which showed features characteristic of orthopoxviruses ( Figure 2, panels A, B) (7).
Sequencing read analysis showed alignment with monkeypox virus. The assembled sequence covered 98% of the closest genome reference on GenBank (accession no. KJ642617.1, a strain from Nigeria), with 99.96% identity. We aligned the consensus sequence with selected representative archived sequences with multiple alignment using Fast Fourier Transform (9) and created a maximum-likelihood tree using RAxML (10) with γ-distributed rate differences and 1,000 bootstrap validation. The virus belonged to the West African clade and clustered with strains from Nigeria with 100% bootstrap support ( Figure  2, panel C). The patient was isolated in a negative-pressure room and remained well throughout admission. He was examined daily for new pustules and evolution of scabs ( Figure 1, panels B-E). By May 24, all scabs had shed, and he was de-isolated and discharged.
Within 24 hours after notification of the suspected monkeypox case, the Ministry of Health contact tracing team established the patient's activities, identified contacts, and determined risk categories. These activities were performed through interviews with the patient and with his contacts. Close contacts were defined as persons who were within 2 meters of the patient for >30 minutes or had physical contact with him or had physical contact with surfaces or materials contaminated by secretions from him from April 30 on (11).
We identified 23 close contacts (19 workshop attendees and 4 hotel staff) and 8 lower risk contacts. Quarantine orders were issued to 22 close contacts on May 9; they were required to remain at home or at a government quarantine facility for the duration of the remaining incubation period (21 days). They were not allowed to come into physical contact with others on the same premises and were monitored for fever and rash >3 times each day through video calls. One close contact, who was well, had left Singapore for Nigeria on May 5; we provided details to the Nigerian International Health Regulations National Focal Point.
Close contacts were offered smallpox vaccination (ACAM2000; Sanofi Pasteur Biologics Co, https://www.sanofi.com) as postexposure prophylaxis. Of the 22 close contacts, 14 received the vaccination, 2 had contraindications, and 6 declined. All vaccinated persons had a scab or ulcer at day 6-8 of review. Side effects included slight fever and mild swelling at the vaccination site; no serious adverse events were reported. Lower risk contacts were placed on phone surveillance twice a day for the remaining incubation period.
Because of the early suspicion of an infectious disease, all healthcare workers who interacted with the patient used personal protective equipment. Ambulance paramedics and Tan Tock Seng Hospital emergency staff had worn N95 masks and disposable gowns and gloves. At the National Centre for Infectious Disease, healthcare workers donned full personal protective equipment (N95 mask, eye protection, disposable headgear, gloves, and sterile disposable gowns). Thus, no healthcare workers were quarantined or removed from work, but they were monitored for symptoms as an added precaution.
We followed up all contacts for 21 days after exposure. Monkeypox did not develop in any contacts, and we found no evidence of secondary transmission in Singapore.

Conclusions
The patient's clinical manifestations of a vesiculopustular rash and uncomplicated illness was similar to monkeypox cases in the United Kingdom and Israel, which were also linked to travel from Nigeria (3,4,12). All exported cases were of the West African clade, which is thought to be milder and less transmissible than the Congo Basin clade (13). Nevertheless, human-to-human transmission had been also demonstrated in Nigeria and the United Kingdom.
Singapore's experience with monkeypox highlights the critical role frontline clinicians play in surveillance of emerging infectious diseases. This situation was similar to the 2016 Zika outbreak in Singapore, when a general practitioner contacted the Ministry of Health about an unusual increase in persons with fever, rash, and joint pains (14). In both instances, the Ministry of Health had informed physicians about the evolving global situation. Public health agencies should prioritize regular communication with healthcare workers as integral to preparedness for emerging infectious diseases.
Unlike previous monkeypox outbreaks, the outbreak in Nigeria affected predominantly urban dwellers and resulted in exported cases to geographically disparate countries (1). Increasing urbanization and better connectivity can lead to the emergence and spread of infections to new areas (15). Our experience with monkeypox highlights the importance of countries investing in preparedness, including maintaining surveillance systems suited to detecting the emergence of infectious diseases globally.