The silent, rapidly unfolding threat of mpox spread via international travel to Southeast Asia: Are we ready?

Abstract

The 2022 mpox (monkeypox) outbreak has been surprisingly large and has raised several novel questions about this disease. New information, such as atypical clinical manifestations and transmission via sexual activities, have been identified. These pose a potential risk of widespread outbreaks due to unusual clinical manifestations and failure to consider mpox as a diagnosis by physicians and the sexual behaviours of some tourists in Southeast Asia. Since Southeast Asia is a popular tourist destination, there is substantial potential for the silent spread of mpox in this region. Consequently, there is an urgent need for effective surveillance measures at points of entry of international travelers to identify suspected cases and their close contacts in order to limit the spread of mpox in Southeast Asia.

Mpox is a re-emerging viral zoonotic disease caused by the mpox virus (MPXV), a DNA virus related to smallpox virus, variola virus, and vaccinia virus, the latter of which is used in the smallpox vaccine. Mpox is endemic primarily in the tropical rainforests of West and Central Africa, where two distinct lineages co-circulate. The Democratic Republic of Congo is considered a hotspot for MPXV. Several outbreaks have occurred since the discovery of the virus in 1958 in Copenhagen and the first human case of mpox was detected in 1971. Transmission leading to outbreaks in Africa results from exposure to wildlife or bushmeat and occurs among members of households with individuals who have MPXV infection. Outbreaks outside Africa have occurred via the importation of wild animals and via infected travellers returning from mpox endemic regions. Outbreaks have been reported in 11 African countries over the past decades [1]. In 2003, the first record of mpox outbreak outside Africa was reported among 71 cases in the US which were related to prairie dogs infected with MPXV from imported African rodents in pet stores [2]. Importation by three international travellers was identified in 2018, with one UK healthcare worker being the first since 2003 to report the spread of mpox outside an outbreak setting related to international travel [3]. Fortunately, there was little evidence of secondary human-to-human spread.

The current mpox outbreak affecting numerous countries is a novel event. Since confirmation in May 2022, an outbreak has been ongoing in non-endemic countries outside Africa. During the 2022 mpox outbreak, evidence has been reported of person-to-person transmission occurring in specific communities through close contact, primarily among men who have sex with men (MSM). Most cases seemingly have no epidemiological link to travel from an endemic country [4,5]. However, mpox can spread in different ways, such as through person-to-person contact with infectious lesions or respiratory droplets. This transmission mode places all sexually active individuals at high risk during an outbreak [[4], [5], [6], [7]]. The clinical presentation of cases associated with the 2022 outbreak has been atypical compared with previously documented reports. Many individuals newly infected with MPXV do not exhibit the classical clinical picture of fever and swollen lymph nodes, followed by cutaneous eruptions and rapidly evolving skin lesions. Usually, eruptions start in the face and extremities with macules that transform into papules over the first few days after infection. The papules grow considerably in size and become oozing pustules that last more than a week before crusting, and scab formation occurs the following week. Patients are considered infectious for the 3-week period that skin lesions are present. In contrast, recently reported mpox cases have exhibited atypical presentations, including lesions that are concentrated in the anogenital region [4,5]. Although the possible role of sexual transmission of MPXV remains unclear, viral DNA has been reportedly detected in seminal fluid [4,7]. Moreover, asymptomatic carriers were reported in some cases. These carriers may play a negligible role in transmission of the virus [8].

At the time of this writing, over 84,000 laboratory-confirmed cases and 75 deaths have been identified in 110 countries. Additionally, despite the downward trend in the past months, a 7-day increase of 48.7% has been observed in early December 2022 before decreasing in following weeks. Singapore declared the first imported case in Southeast Asia during the present outbreak, with 38 mpox cases detected in the region as of 5 January 2023 (Singapore, Vietnam, Indonesia, Philippines and Thailand) (https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html). Interestingly, the first autochthonous case in Singapore was identified 2 weeks after detection of the first imported case, with no direct epidemiological link between these two cases. This phenomenon reflects the looming threat of a potential outbreak that could easily spill over to the entire Southeast Asia region. Although recent mathematical modelling suggests no direct association of mpox outbreaks with air travel, these models could be used to assess the probability of an indirect association with air travel [9]. The situation throughout Southeast Asia is fluid, which raises public health concerns regarding the possibility of importing mpox via international travel, subsequently leading to community transmission, especially in places where tourism has resumed during the ongoing COVID-19 pandemic.

Amidst the COVID-19 pandemic, with greater availability of vaccines and health information, international tourism is expected to continue a gradual recovery in 2022. Several countries have lifted their travel restrictions to promote tourism, especially in Southeast Asia. According to the Thai Ministry of Tourism and Sports, over ten million international tourists arrived in Thailand by December 2022, with more than 50% from European countries (https://www.bloomberg.com/news/articles/2022-12-10/thailand-hits-tourism-goal-as-foreign-arrivals-top-10-million). Over the same period, 3.92 million international tourists arrived in Indonesia (https://kemenparekraf.go.id/statistik-wisatawan-mancanegara). This was a considerable increase from the previous year when most travellers were arriving from Australia, reflecting the increasing number of international tourist arrivals in Southeast Asia. The increasing demand for international travel in this region increases the threat of mpox importation to the region, which could lead to outbreaks. Several countries in Southeast Asia have developed control measures for inbound international travellers to intervene against importation of MPXV. A summary of mpox control measures at points of entry in each country of Southeast Asia is demonstrated in Table 1 .

Table 1.

Mpox control measures at points of entry in Southeast Asian countries (as of 15 December 2022) (number of cases retrieved from https://www.cdc.gov/poxvirus/monkeypox/response/2022/world-map.html).

Country	Control measurements at points of entry	Case/suspected case/contact management	2022 outbreak cases	Previous cases	Sources
Thailand	-Alert disease control checkpoint at airports -Additional screening for high-risk inbound travellers	-People with suspect symptoms can directly call the Department of Disease Control hotline 1422 -Suspected case will be isolated in the single isolation room	12	0	Thai PBS World ‘Two more monkeypox cases confirmed in Thailand’ (https://www.thaipbsworld.com/two-more-monkeypox-cases-confirmed-in-thailand/) Tourism Authorities of Thailand Newsroom ‘Thailand fully opens for tourism, takes precautions to prevent Monkeypox transmission’ (https://www.tatnews.org/2022/05/thailand-fully-opens-for-tourism-takes-precautions-to-prevent-monkeypox-transmission/) Bangkok Post ‘Officials set up monkeypox screening’ (https://www.bangkokpost.com/thailand/general/2357789/officials-step-up-monkeypox-screening)
Laos	-Screening international arrivals and request travel history -Travelers who have visited countries where the virus is endemic within 21 days, such as in Central and West Africa, will be denied entry into Laos	-No available data on case/suspected case/contact management	0	0	The Laotian Times ‘Laos Monitors Monkeypox Among Tourists’ (https://laotiantimes.com/2022/05/26/laos-monitors-monkeypox-among-tourists/)
Vietnam	-The Ministry of Health requires localities to monitor and detect suspected cases at border gates and medical facilities -Checks will be enhanced for those coming from outbreak countries. -Suspected cases will be isolated and sent to hospital	-When detecting suspected cases, the healthcare facility should immediately coordinate with the local Institute of Hygiene and Epidemiology and Pasteur Institute to diagnose and confirm the case	2	0	Vietnam Plus ‘Health Ministry issues guidance on monkeypox prevention, control’ (https://en.vietnamplus.vn/health-ministry-issues-monkeypox-monitoring-guidance/236065.vnp) Vietnam Plus ‘Vietnam prepares diagnosis, treatment capacity in response to monkeypox’ (https://en.vietnamplus.vn/vietnam-prepares-diagnosis-treatment-capacity-in-response-to-monkeypox/237591.vnp?utm_source=link.gov.vn#source=link.gov.vn)
Cambodia	-Airport staff should observe and report to health authorities on international travellers who have rash or blisters with fever and a history of travel from mpox endemic areas -Increased vigilance on mpox screening in border provinces	-All hospitals and health centres must track and report any suspected cases and continue follow-up investigation -Instruct people with suspected symptoms to report by contacting 115 or going to the nearest health centre	0	0	The Phnom Penh Post ‘Border provinces all on alert with Monkeypox in Thailand, Vietnam’ (https://www.phnompenhpost.com/national/border-provinces-all-alert-monkeypox-thailand-vietnam) The Phnom Penh Post ‘Kingdom tightens monkeypox controls after arrest of patient’ (https://www.phnompenhpost.com/national/kingdom-tightens-monkeypox-controls-after-arrest-patient)
Myanmar	-No available data on disease control at point of entry	-Inform the public to report to relevant departments if they develop mpox symptoms	0	0	Ministry of Health (Myanmar) ‘Update On Monkeypox Virus (29-7-2022)’ (https://moh.nugmyanmar.org/update-on-monkeypox-virus-29-7-2022/) Myanmar ITV ‘Monkeypox prevention: Ministry of Health making preparations’ (https://www.myanmaritv.com/news/monkeypox-prevention-ministry-health-making-preparations)
Malaysia	-Suspected or self-referral cases to be reported to health personnel at the health screening area at the entry point and screened for mpox infection -Establishing management plans for suspected cases aboard flights/cruises/ships as well as health monitoring advice for travellers seated close to a suspected case -Reactivation of MySejahtera application for mpox surveillance for travellers from countries with reported cases of mpox	-All suspected, probable, or confirmed mpox cases must be notified to the District Health Office within 24 h via phone call -All suspected, probable, or confirmed mpox cases must undergo investigation using a standard form provided by the Ministry of Health -Exposed individuals with a high risk of infections must be observed for 21 days, from the date of last exposure to a confirmed case, for any mpox symptoms and signs	0	0	Ministry of Health (Malaysia) ‘Interim Guidelines on Monkeypox Management in Malaysia No. January 2022 (updated on 23 May 2022)’ (https://www.moh.gov.my/index.php/database_stores/attach_download/312/445) Tao CC et al., 2022 (https://tropmedhealth.biomedcentral.com/articles/10.1186/s41182-022-00479-4)
Singapore	-Advise individuals with fever and vesicular rash to seek immediate medical attention and inform about recent travel history	-All suspected cases should be reported to Ministry of Health immediately through surveillance Duty Officer of the Communicable Diseases Division and filling the MD131 Notification of Infectious Diseases Form. -Individuals who have close contact with a confirmed mpox case will be quarantined for 14 days, followed by seven days of monitoring for symptoms. -Should close contacts report symptoms that are suggestive of mpox infection, they will be medically assessed and may be conveyed to the National Centre for Infectious Diseases for further evaluation	19	1	Ministry of Health (Singapore) ‘Updated measures for monkeypox’ (https://www.moh.gov.sg/news-highlights/details/updated-measures-for-monkeypox) Ministry of Health (Singapore) ‘Monkeypox’ (https://www.moh.gov.sg/diseases-updates/monkeypox) National Centre for Infectious Diseases ‘Monkeypox’ (https://www.ncid.sg/Health-Professionals/Joint-MOH-NCID-Guidances/Pages/Monkeypox.aspx)
Indonesia	-Develop webinar on mpox for healthcare workers including those from Point of Entry offices -Raising awareness for border patrol officials and port health offices through the MoH Circular -Install thermal scanner and increased monitoring vigilance at Bali airport	-Increase vigilance among healthcare workers and intensify surveillance, case and cluster investigation, and contact tracing -Suspected cases should be reported to district/provincial health officers	1	0	World Health Organization South-East Asia (Indonesia) ‘Increasing preparedness and prevention measures for monkeypox’ (https://www.who.int/indonesia/news/detail/05-06-2022-increasing-preparedness-and-prevention-measures-for-monkeypox) Ministry of Health (Indonesia) ‘Prevention and Control Guidelines Monkeypox’ (https://infeksiemerging.kemkes.go.id/document/download/5qo6p2jOp2) The Jakarta Post ‘Bali airport on alert following first monkeypox case’ (https://www.thejakartapost.com/indonesia/2022/08/24/bali-airport-on-alert-following-first-monkeypox-case.html)
Brunei Darussalam	-No available data on disease control at point of entry	-Issuing document that advice the public and healthcare workers about mpox preventive measures.	0	0	Ministry of Health (Brunei Darussalam) ‘Everything you need to know about monkeypox’ (https://www.moh.gov.bn/Shared%20Documents/DOWNLOADS/EVERYTHING%20YOU%20NEED%20TO%20KNOW%20ABOUT%20MONKEYPOX.pdf)
Philippines	-The Bureau of Quarantine will conduct symptom screening among international travellers from countries that are reporting mpox cases -Quarantine centres are to be located near the point of entry	-Suspected, probable, or confirmed cases of mpox at the point of entry are to be reported to the Department of Health within 24 h -The Research Institute for Tropical Medicine will be the main isolation facility for suspected, probable, and confirmed mpox cases	4	0	Bureau of Quarantine, Department of Health (Philippines) ‘Advisory: Monkeypox’ (https://quarantine.doh.gov.ph/advisory-monkeypox/) Department of Health (Philippines) ‘Interim Technical Guidelines for the Implementation of Monkeypox Surveillance, Screening, Management and Infection Control’ (http://bit.ly/MonkeypoxFacts)
Timor-Leste	-No available data on disease control at point of entry	-Prepare vigilance epidemiological team in case of mpox outbreak	0	0	Tatoli Agência Noticiosa de Timor-Leste ‘TL-MoH set up the strategy to combat Monkeypox virus’ (https://en.tatoli.tl/2022/07/19/tl-moh-set-up-the-strategy-to-combat-monkeypox-virus/10/)

International travel poses an increased risk of the spread of sexually transmitted infections (STIs). Up to 20% of travellers have reported having travel-associated casual sex, with half of travellers engaging in unprotected sexual intercourse [10]. As previously reported, individuals who engage in unprotected intercourse and attain new partnerships during travel have a greater risk of contracting STIs [10]. Studies conducted in Thailand demonstrated that up to 79% of travellers who presented to sexual health clinics acknowledged engaging in casual sex during their visit to the country, averaging up to 10 partners [11]. Moreover, the use of dating applications has become popular among travellers abroad, through which they can easily find sexual partners close to their geographical location, which might be considered high-risk sexual behaviour [12]. Although mpox is not yet considered an STI, the 2022 mpox outbreak has been linked to sexual activities, given that transmission requires close physical or prolonged contact. High-risk sexual behaviours may contribute to the rapid spread of mpox in Southeast Asia with reopening of the tourism sector.

Stigmatization and discrimination are ongoing challenges throughout Southeast Asia. Initial reports during the current mpox outbreak have mostly involved MSM; however, it is crucial to avoid labelling the infection as being limited to a particular population. Such labelling could lead to unnecessary stigmatization of certain individuals and groups, similar to what has occurred during the HIV/AIDS epidemic. Moreover, individuals outside of stigmatized groups may falsely believe that they are not at risk and may ignore public health guidance and alerts. Travellers are hesitant to notify local authorities because reporting oneself as a suspected case would lead to being placed in quarantine, contact tracing, and epidemiological investigation. Thus, some sensitive information may go unreported or may be withheld, including information regarding sexual activities and contacts. Further, mpox is typically a self-limiting illness from which patients recover completely within 2–4 weeks. Therefore, individuals with lesions may fear seeking medical attention, increasing the risk of disease spread.

It is essential to highlight that healthcare providers working in travel clinics, sexual health clinics, emergency paramedical services systems, and hospital emergency departments are likely to encounter patients needing evaluation for mpox. Therefore, healthcare workers should implement standard precautionary measures and perform risk assessment to evaluate the need for transmission-based precautions. The public health sector must urgently provide mpox information to the general population, especially those most at risk of contracting the disease. Healthcare workers managing confirmed or suspected cases must wear full PPE, perform hand hygiene according to contact and droplets precaution [13].

The threat of mpox transmission means that all countries should increase surveillance and laboratory capacity to detect cases in a timely manner. As major tourist destinations, Southeast Asia nations should prioritize measures to increase awareness, manage risk perception, maintain trust, and pro-actively assist vulnerable individuals in making informed decisions. The development of national guidelines should include recommendations on identifying and communicating with travellers and critical audiences and avoiding stigma. The authorities should prepare mpox vaccine policy and prioritize to vulnerable population. At popular tourist destinations where gatherings and events are frequent, key messages should be disseminated, such as the symptoms of mpox, transmission information, and prevention measures.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Wasin Matsee: Conceptualization, Supervision, Validation, Writing – original draft, Writing – review & editing. Sakarn Charoensakulchai: Conceptualization, Writing – original draft. I Made Ady Wirawan: Supervision, Validation, Writing – review & editing. Hisham A. Imad: Supervision, Validation, Writing – review & editing.

Declaration of competing interest

The authors declare that there are no competing interests.