From Volume 49, Issue 8, September 2022 | Pages 683-687
Monkeypox (MPX), a rare zoonotic disease, endemic to some African countries is now spreading in non-endemic regions, including the UK. So far, it has been reported in 93 countries with over 38,000 global cases, although the signs are that the disease may be plateauing in UK. The outbreak was declared a public health emergency of international concern by the World Health Organization (WHO). Monkeypox virus (MPXV), belongs to the family
Monkeypox (MPX), a zoonotic infection, caused by the monkeypox virus (MPXV), which is a DNA virus, is spreading around the world at an alarmingly rapid rate. A re-emergent viral infection, it was first identified in monkeys in a laboratory in Denmark in 1958, but it is typically found in rodents and other animals. The first case of monkeypox in humans was first described in 1970.1
Surprisingly, the original source of the disease is still a mystery. In fact, the World Health Organization (WHO) is planning to rename the MPXV due to the concerns for the stigmatization of monkeys, particularly as the animals have little to do with disease spread. Since the 1960s, the disease has been mainly endemic in the African continent with occasional sporadic outbreaks in western countries. Previous MPX cases in the UK were either imported from such endemic regions or through contacts with documented epidemiological links to the imported cases.
WHO declared the current monkeypox outbreak ‘a public health emergency of international concern’ on 23 July 2022, although the disease has been designated as an airborne ‘high consequence infectious disease (HCID)’ by the UK Health Security Agency (UKHSA), since 2018.2 Between 2018 and 2021, seven cases of MPX were identified in UK, of which three were attributed to onward transmission within the UK.3,4 At the time of writing (20 August 2022) there were over 3000 cases in the UK, with the vast majority in England (>2800 cases) (Figure 1).5
MPX is not as contagious or infectious as SARS-CoV-2, the agent of COVID-19, and is unlikely to pose a major threat to the dental team, particularly in UK, for three main reasons. First, the MPXV is not readily transmissible through the airborne route, although such a possibility always exists. Secondly, the disease prevalence in the UK relative to the population density is still relatively low, with signs of plateauing (Figure 1), and last, but not least, dental practitioners in UK are now known to uniformly implement strict standard, contact, and droplet infection control precautions in their clinics, mainly due to the COVID-19 pandemic. Nevertheless, as healthcare professionals, the dental team should be cognizant of the key aspects of this disease as appertaining to dentistry, such as its transmission routes, clinical manifestations, as well as diagnostic and prevention strategies, as discussed below.
A number of so-called pox diseases, similar to MPX are known, some confined to animals and the others to humans. For instance, cow, sheep, fox, and fowl pox, are the most well-recognized animal pox diseases, while smallpox, chickenpox and monkeypox are essentially human diseases.6
There are currently two human pox illnesses that are prevalent in the global community, the relatively common chickenpox, and the re-emerging MPX. Incidentally, smallpox infection, is worthy of mention here for historical interest as it is the first human disease eradicated through a successful global vaccination programme. The main differentiating features between chickenpox and MPX are outlined in Table 1.
| Monkeypox | Chickenpox | |
|---|---|---|
| Agent | Monkeypox virus |
Varicella zoster virus |
| Spread (similar) | Close contact, respiratory droplets, contact with skin lesions, recently contaminated objects | |
| Contagiousness | High | Relatively low |
| Incubation period | Average 7−14 days, but can range from 5 to 21 days | 10−21 days |
| Illness | Mild illness with distinctive swollen lymph nodes (lymphadenopathy). Initial symptoms include fever, headache, muscle aches, backache, chills and exhaustion | Swollen lymph nodes appear rarely, if ever. Other symptoms are fever, tiredness, headache, and loss of appetite |
| Symptoms | Lasts 2−4 weeks | Lasts up to 2 weeks, commonly subsides in 1 week |
| Fever | 1−5 days before rash | 1−2 days before rash |
| Rash characteristics | Usually begins on the face then spreads to other parts of the body, including palms and soles. The rash eventually forms a black scab that falls off | Itchy, blister-like rash, first on the chest, back, and face and then over the entire body. Absent on palms and soles, and unlikely to form scabs |
| Oral lesions | Affects the oral mucosa in 25–70% of cases as macules and vesicles. Lips and peri-oral areas may also be affected | May appear in the mouth before skin lesions, on either the keratinized or non-keratinized mucosa |
| Fatality | Some strains cause severe disease, with fatality in 1–11% | Rare; any fatalities seen are typically in patients with comorbidities |
| Isolation | For 3 weeks. Avoid contact with immunosuppressed people, pregnant women and children younger than 12 years | Rarely necessary, unless lesions are severe and widespread |
| Prevention | The traditional smallpox vaccine is protective against MPX; a vaccine approved for the prevention of MPX called Imvanex is available in UK. It is based on a strain of vaccinia virus. | Chickenpox or varicella vaccine (two doses 4–6 weeks apart) contains attenuated live varicella zoster virus. A combination vaccine of measles, mumps, rubella and varicella (MMRV) is now available |
| Vaccine recommendation for HCWs | Desirable for those in MPX-endemic regions or in the case of localized outbreaks. | Recommended by WHO for HCWs who are not immune due to natural infection |
Sources: various, including World Health Organization (WHO) and US Centres for Disease Control and Prevention (CDC) and reference 7.
HCW: healthcare worker; MPX: monkeypox.
MPXV is a double-stranded DNA virus that belongs to the family Orthopoxviridae, and has a characteristic ultrastructure with mature mulberry shaped viral particles (Figure 2). Although MPXV has a low mutation rate, under certain selective pressure, adaptive mutations of the virus may occur, which enhance its transmissibility.
The virus is known to exist in two distinct clades in Africa, Clade 1 and Clade 2, both originating in Africa, which were, until very recently, called the Congo Basin and the West African clades, respectively. The prognosis of MPX is generally dictated by the origin of the clade, with Clade 2 infections having a more favourable prognosis with a case fatality of less than 1%, in contrast to the more lethal, Clade 1 with up to 11% case fatality, particularly in unvaccinated children.6
The commonest means of MPX transmission is by close skin-to-skin contact with an infected person's pus-filled lesions, through auto-inoculation of viral particles. Other routes of transmission are through contaminated objects such as bedding, clothing or eating utensils or, very infrequently, through exposure to respiratory droplets at close range. The main portals of viral entry are considered the mucous membranes, non-intact skin, open wounds and the respiratory tract.7,8
Although not considered a sexually transmitted disease as yet, MPX is clearly transmitted through sex. Over 90% of recent cases have primarily involved men who have sex with men.8 Finally, other transmission routes, such as mother-to-child transmission or nosocomial infection in hospital settings, have been rarely documented. In short, relative to the SARS-CoV-2, the agent of COVID-19, which is the most contagious virus known to date, MPXV is very poorly transmissible.
Despite the fact that the vast majority of MPX cases have involved close contact between people with visible lesions or other symptoms, there are a few reports of totally asymptomatic individuals testing positive for the disease without obvious symptoms.9 This is clearly a concern from a public health perspective, and not least because of its implications for the practice of dentistry. Occasional, animal-to-human transmission of MPX has been reported by bites or scratches from infected animals, such as small mammals including rodents (rats, squirrels) and non-human primates (monkeys, apes), or through bush meat preparations.7
The portal for MPX viral entry could be via the oropharyngeal, genital or anorectal mucosa or intradermal routes. The virus replicates at the inoculation site and spreads to the lymph nodes during the initial viraemic phase. Following this incubation period, the virus spreads to other organs including the skin.
The incubation period typically lasts between 7 and 14–days and even up to 3 weeks. The primary phase of clinical sickness typically lasts between 1 and 5 days, during which time patients may have a fever, headache, back pain, muscle aches, fatigue and lymphadenopathy (Figure 3). The latter is a major feature of this disease.8 This is followed by a second phase, which begins 1 to 3 days afterwards, when the fever subsides, and the characteristic rash emerges. The rash usually spreads centripetally to other parts of the body over a period of 2–3 weeks, and progresses through typical macular, papular, vesicular, and pustular stages (Figure 4). Finally, the pustular blisters break, forming a black scab that eventually falls off leaving a crusted lesion.
The lesions usually have a diameter of 0.5–1 cm, and can range from a single lesion to several thousands. In addition to the early presentation of lesions in the oral mucosa, they may manifest in the conjunctivae, cornea or genitalia. MPX lesions are firm or rubbery, well circumscribed, deep-seated, and often develop umbilication (with a black dot on the top of the lesion) (Figure 5). Patients are not considered infectious once the crusts have fallen off, after about 4 weeks.8
The mucosal and skin lesions are usually self-limiting, and the patient usually fully recovers. Nevertheless, owing to comorbidities and other generalized conditions, such as malnutrition and immunocompromised states, particularly in resource-poor regions, MPX can lead to complications, such as pneumonitis, sight-threatening keratitis, encephalitis, secondary bacterial infections and sometimes, death.10
Typically, serum antibodies for MPX are detected around 2 weeks post-exposure, when oral or skin lesions appear. The recommended test for identifying the disease is based on nucleic acid amplification testing (NAAT), using real-time or conventional polymerase chain reaction (PCR), for detection of unique sequences of viral DNA.11
Noteworthy from a dental context is that the primary presentation of MPX is likely to be on the oral mucosa as pink macules or papules. In some studies, oral ulcers have been recorded in almost one-quarter of MPX patients.12 Nevertheless, papules (or indeed vesicles) are infrequently seen intra-orally as they immediately burst due to tongue movements and chewing, with a residual crateriform red lesion formation. If severe, oral ulcers may impair a patient's ability to eat and drink, causing dehydration and malnutrition. Peri-oral papules that were ulcerated have also been reported in the current outbreak.7
For these reasons, the dentist may be the first to note the eruptions during routine examination of the oral mucosa, particularly because the patient may be unaware of their existence as the lesions are not painful in the early macula/papular phase.
Thus, a high degree of suspicion should be maintained during routine examination of the oral mucosa by personnel working in areas with a high incidence or prevalence of the disease, especially for those patients who present with generalized lymphadenopathy. Differential diagnosis of MPX includes other macular/papular lesions due to the varicella-zoster virus, including chickenpox and herpes zoster (shingles).13 However, the appearance of the umbilicated monkeypox lesions differs significantly from the itchy maculopapular lesions of chickenpox (Table 1). Additionally, herpes zoster lesions have a pathognomonic dermatomal distribution, characterized by mid-line demarcation of the eruptions.13
Finally in this context, the dental team should possess a strategic plan on how best to manage an eventuality when a suspect MPX patient presents at the clinic. This should include the advice that should be given to the putative patient, the details of referral centres in the area, and advice to immediate family and the close contacts.
To date there has been no documented case of MPX spread in a dental setting. Nevertheless, as its spread is generally through direct or indirect contact with body fluids or lesion material, disease transmission in the dental clinic environment cannot be ruled out in disease-prevalent areas. This is highly plausible as dental practice demands prolonged close contact with patients at close quarters, generally using aerosol generating procedures (AGPs). As such, standard infection prevention and control (IPC) precautions recommended in the National IPC Manual for England should be strictly adhered to.14
These include adherence to standard, contact and droplet infection control precautions, including fluid-resistant surgical masks (FRSM), such as as N95 masks, other fluid-resistant attire, and eye protection. Additionally, aerosol-generating procedures should be withheld particularly when managing suspect patients with MPX.
It is worth emphasizing that elective dental treatment in patients with probable, or confirmed cases of MPX should be postponed until the disease is excluded, or the patient is no longer infectious. In the unlikely event of the need for emergency dental treatment of such a patient, then, as recommended by UKHSA guidelines, the patient should be given a fluid-resistant type of surgical mask, and asked to await treatment in a restricted area, and be attended to in a separate surgical area. Suggested PPE when treating such a patient would include an FFP3-type respirator, and fluid resistant gowns, gloves and eye protection. Special care should be taken to cover any exposed skin lesions of the patient throughout the patient management process, and precautions taken to avoid touching any materials that have come into contact with a patient with MPX. After the surgical procedure, cleaning and disinfecting of all the used material should be strictly performed in the ‘dirty’ areas of the dental facility. Careful handling, collection and disposal of all PPE used during the treatment episode, both by the dental team, as well as the patient, is essential.
Finally, in this context, if indeed the patient is confirmed as having MPX, aftercare of such patients should be undertaken through teleconsultation. Pregnant women and severely compromised individuals should not provide care for patients with suspected MPX. 14
In the event of an exposure, vaccines developed against smallpox offer a high degree of protection against MPX. A third-generation smallpox vaccine, under the product name Imvanex (Bavarian Nordic A/S, Denmark) is available in the UK (Jynneos in USA) for prophylaxis against the disease.15 Its active component is an attenuated vaccinia virus (modified Vaccinia Ankara-Bavarian Nordic [MVA-BN]). Vaccination of close contacts has successfully limited transmission in previous outbreaks. The vaccine must be administered as early as possible after exposure to be efficacious. The vaccine is indicated for healthcare and laboratory workers likely to be exposed to patients with MPX. 15
The vaccine is currently in short supply and hence, a strategy known as ‘dose sparing’ for stretching out vaccine supplies has been currently approved in the USA and Europe, where one-fifth of the regular dose is given by the intradermal route to the vaccinee.
Disease management is essentially symptomatic in the event of an ensuing MPX infection due to self-limiting nature of the disease. Nevertheless, the antivirals cidofovir, brincidofovir and tecovirimat are available for patients with comorbidities, such as immune deficiencies.16 Passive immunization with vaccinia immune globulin (6000 UI/kg to 24,000 UI/kg) has been successful.6
MPX outbreak continues to grow globally with over 38,000 cases recorded at the time of writing (20 August 2022), although its transmission rate appears to be slowing down in the UK. Currently MPX has become a significant travel-related disease, and all healthcare workers, including dental personnel, should remain vigilant and be prepared to manage patients who may present wittingly or unwittingly with orofacial or other symptoms of MPX. The signs are that, in the longer term, MPX will be another short-lived sporadic viral ‘visitation’ with little likelihood of being endemic, at least, in the West.
