A case of mpox (formerly monkeypox) was diagnosed in Aotearoa New Zealand in early July 2022. Mpox is a zoonotic viral illness rarely seen outside Central and West Africa, previously. However, since May 2022 an increasing number of non-endemic countries have reported locally acquired cases of mpox. Over 85,000 cases have been reported from 110 countries globally including 83 deaths as of 24 January 2023.[[1]] On 23 July 2022, the World Health Organization (WHO) declared the current mpox outbreak a Public Health Emergency of International Concern.[[2]] Globally, the incidence of mpox is declining. As of 12 January 2023, 41 cases have been reported in New Zealand, including 31 cases that were locally acquired.[[3]]

New cases of mpox continue to be reported and all clinicians working in sexual health, primary care, emergency, and urgent care need to be vigilant for mpox, be familiar with diagnostics and the approach of supportive clinical management, and be aware of public health requirements regarding isolation and clearance. A sensitive approach is required to avoid stigma and discrimination. There have been numerous publications since the mpox outbreak began. We aim to consolidate the salient information with a clinical focus for the New Zealand clinician.

Causative agent and epidemiology

Mpox virus (MPXV) is a DNA virus from the Orthopoxvirus genus of the Poxviridae family. It is the most common Orthopoxvirus causing infections in humans since the eradication of smallpox in 1980. There are two clades of MPXV, recently renamed Clade I (formerly Central African or Congo Basin clade) and Clade II (formerly West African clade). Several variants of subclade IIb are responsible for the current outbreak.[[4]]

The natural reservoirs of MPXV are unknown. Several factors, including the phylogenetic evolution of the virus, changing rodent-to-human interactions, and increased interconnectivity of an immune-naïve human population are all thought to have contributed to the increased human-to-human transmission of MPXV.[[5]]

Bites, scratches, and consumption of infected meat from MPXV-infected animals can transmit the virus to humans. Previously, it was thought that human-to-human transmission occurred through respiratory droplets, direct contact with mucocutaneous lesions and scabs of an infected individual, and fomite transmission (e.g., through recently contaminated bedding).[[6]]

While laboratory testing has demonstrated MPXV to be present in pharyngeal samples of cases, skin-to-skin contact, especially when there is microtrauma or skin friction with direct inoculation is the dominant route of transmission during this outbreak.[[7]] It is unlikely that an infected human will pass on mpox through the contamination of food subsequently consumed by others.[[8]]

Transmission to healthcare workers is extremely rare when personal protective equipment (PPE) is used, but has been reported following presumed inhalation of infected skin squames from contaminated bedding[[9]] and percutaneous exposure from a needle used to obtain a cutaneous sample.[[10]] There is limited data on the risk of vertical transmission of MPXV, but mpox can be transmitted to the fetus during pregnancy, and through close contact during and after birth, as well as when breastfeeding. There have been reports of miscarriage and stillbirth in mpox-infected pregnant individuals.[[11]] Serial interval studies have shown asymptomatic transmission and a large proportion of transmission occurs as much as 4 days before the patient is symptomatic.[[12]]

Among cases with known data, WHO reports 86.1% of cases during the 2022 outbreak have been in individuals who identify as men who have sex with men (MSM). “Sexual encounter” is reported as the most common mode of transmission (70.7%). “Party setting with sexual contact” (59.1%) was the most commonly reported situation for infection. The vast majority of cases have been in men between the ages of 30–39 years. Where HIV status is known, 51.4% of infections have been in individuals with known HIV infection.[[1]]

As of 25 January 2023, there have been 41 confirmed cases of mpox in New Zealand. Ten cases acquired their infection overseas and 31 acquired their infection locally. Cases have been reported from Auckland, Bay of Plenty, Canterbury, Capital and Coast, Waikato, Waitematā, and Southern districts. Where data on sexual behaviour were available, the majority (36) were reported to identify as men who have sex with men (MSM). Case ethnicities were reported as NZ European, Asian, Māori, Pacific peoples, and Other. Six cases were admitted to hospital. (J Scott, ESR Health Intelligence Team, email communication, January 25, 2023).

Clinical features

The incubation period of mpox is between 5 and 21 days, with a mean incubation period during this outbreak of around 7.6 days.[[12]] The illness typically lasts 2–4 weeks. Normally, mpox illness usually commences with a prodromal phase (typically 1–3 days) with constitutional symptoms such as fever (57.8%), headache (31.3%), fatigue (29%), lymphadenopathy (29.7%), myalgia (27.8%), and sore throat (11.5%).[[1]] This is followed by a rash (85.1%), which typically first appears on the face and then spreads quickly in a centrifugal distribution, with more lesions on the face and extremities, than trunk and abdomen. Historically the lesions have been described as monomorphic in nature, progressing sequentially through the stages of macular, papular, vesicular, and pustular appearances before crusting over and desquamating. A person is no longer considered infectious once re-epithelialisation occurs.

A notable feature of the current outbreak is the non-classic presentation in the majority of cases (Figure 1).[[7]] Many individuals have no prodrome, or systemic features may follow the initial lesions. Most have presented with less than 20 lesions, while many have only one or two skin lesions, which are common in the genital area. Lesions may be focussed in the region of inoculation, and are predominant in the anogenital region, where they may be associated with symptoms of anorectal pain, proctitis, tenesmus, or diarrhoea. Many have also presented with oropharyngeal symptoms of pharyngitis, odynophagia, epiglottitis, and oral or tonsillar lesions. Localised lymphadenopathy may occur with the lesions. Macular-papular rashes and polymorphic lesions have also been common.[[7,13,14]] There have also been reports of asymptomatic mpox during this outbreak.[[12,15]] Concomitant sexually transmitted infections (STIs) and HIV (including acute seroconversion) are common among individuals diagnosed with mpox during this outbreak.[[16]]

In New Zealand, cases have presented with lesions on fingers, hands, thighs, genitals, perianal and oral cavity.

Mpox lesions often appear non-specific, with similarities to chickenpox, primary and secondary syphilis, hand, foot, and mouth disease, localised and generalised herpes simplex, molluscum contagiosum, and impetigo, amongst others. These differential diagnoses also need to be considered.

The clinical course of the illness is determined by an individual’s prior smallpox vaccination status, age, and other factors such as pregnancy. Complications associated with mpox include secondary bacterial superinfections and sepsis, encephalitis, conjunctivitis, keratitis (causing corneal scaring and blindness), pneumonia and, rarely, deaths (1–10%; based on the clade of infection).[[6]] Other serious complications seen during this outbreak include severe penile oedema leading to phimosis and paraphimosis; abscesses requiring drainage (e.g., tonsillar abscesses causing airway compromise); significant proctitis, and rectal perforation. The most common reasons for hospital admission are severe rectal pain and severe penile oedema.[[13,14]]

Evidence identifying risk factors for severe disease is limited, but more severe cases have been seen in children, those with conditions associated with immune deficiencies (including advanced HIV), and individuals with high mpox viral loads.[[17,18]] There is limited experience with mpox in pregnancy, although there are reports of adverse fetal outcomes.[[19]]

View Figures 1 and 2.

Diagnosis

Mpox was declared a notifiable infection in New Zealand in June 2022. The New Zealand Ministry of Health – Manatū Hauora has provided a case definition for Mpox in New Zealand. This is regularly reviewed and updated for clinicians.[[3]]

All cases of suspected mpox infection will require a detailed history (including exposure and sexual history) and a thorough clinical examination. The differential diagnoses described earlier in this article should be considered in any suspected case and investigated accordingly.

Currently, mpox testing is recommended for people who fulfil both the clinical and epidemiological criteria, as in Figure 2, or at the request of the Medical Officer of Health. Given the low risk for mpox outside of groups at risk (summarised above), widespread testing is currently not advised. However, due to the varied presentations, maintaining a high index of suspicion and a low threshold for testing in at-risk populations especially gay, bisexual or other men who have sex with men (MSM) is important. It is also likely that clinicians will occasionally see cases among individuals outside established risk groups. Clinicians should refer to the Manatū Hauora website for the latest recommendations.[[3]]

Consultation for assessment and mpox testing is free in primary care as well as sexual health clinics in New Zealand. HealthPathways have been updated with local contacts for testing and advice.

The use of hard stem swabs is recommended for taking sufficient scrapings of dry lesions or ulcers and should be collected in a universal or viral transport medium. Direct detection of MPXV nucleic acid material through molecular methods like polymerase chain reaction (PCR) from mpox lesions (deroofed pustules/ulcers/scabs) seen on the skin, oral mucous membranes, and anus/rectum is the mainstay of diagnosing mpox.[[20]]

The use of PPE including eye protection, gown, gloves, and masks (P2/N95) is recommended for assessment of a suspected case of mpox.

Current Manatū Hauora guidelines recommend isolation pending test results for high-risk patients with advice to avoid close contact with others including sharing bedding or clothing. High-risk patients include those with a very high index of suspicion for mpox, oral mucous membrane lesions, lesions unable to be covered, systemic symptoms, or who are are immunocompromised. All others awaiting test results should be advised to avoid people at high risk of serious disease and to isolate if they develop any high-risk features. All patients should be advised to refrain from sexual or intimate contact and to inform any healthcare facilities before seeking medical care.

It is important that anyone tested for mpox is also offered testing for other STIs, including HIV and syphilis, due to high rates of concomitant STIs. Clinicians should consider the need for HIV prophylaxis as patients at risk of mpox may also be at risk of HIV.

Management

Supportive care

Most patients require only supportive care, as the infection is self-limiting for the majority.  Specific attention to pain management, skin care, oral care, nutrition and hydration may be required. Many will also require the management of proctitis with agents used to treat hemorrhoids (e.g., lignocaine gel and stool softeners). Regular sitz baths may be helpful. Patients should be counseled to avoid touching their eyes to prevent autoinoculation of the eye. Secondary bacterial infection may require antibiotic therapy.

Hospital admission and antiviral therapy should be considered for those with severe disease (e.g., those with extensive lesions, haemorrhagic or necrotic lesions); or where lesions involve anatomic sites which might result in severe sequelae from scarring or strictures, such as ocular disease, neurological sequelae, urethral involvement requiring catheterisation or severe anorectal involvement interfering with bowel function.

Antivirals

No specific treatments directed against the MPXV have yet been developed; however, some existing therapies for other pox viruses are expected to have activity and have been repurposed. Direct-acting antivirals such as tecovirimat and cidofovir/brincidofovir, together with vaccinia immunoglobulin (VIGIV) have been included in international treatment guidelines.

Tecovirimat (TPOXX®), an oral antiviral taken twice a day for 2 weeks, was initially approved for smallpox treatment by the Food and Drug Administration (FDA) in 2018 following concerns that smallpox may be used as a biological weapon.[[22]] Subsequently the European Medicines Agency also approved use in 2022 for orthopox infections including smallpox, cowpox, mpox, and complications related to smallpox vaccinations.

Initial reports from the US and other countries indicate that tecovirimat is well tolerated, with headache and nausea being reported as the most common side effects. The efficacy of tecovirimat for mpox is not known and randomised control studies are underway in multiple countries to determine this.[[23,24]]

Internationally, tecovirimat use has been prioritised for people who have, or are at risk of progression to, severe disease (such as severely immunocompromised people, pregnancy and breastfeeding, children <8 years old, those with skin integrity issues, e.g., severe dermatitis), and in some settings considered for use where the anatomical location of the lesion is concerning for secondary sequelae (e.g., stricture development).[[21]] Use of the other antivirals, cidofovir, and brincidofovir, is limited by the risk of renal and hepato-toxicity, respectively. Consideration for use of directed therapy in New Zealand should be made in conjunction with a sexual health or infectious diseases physician as per local HealthPathways.

Contact tracing and isolation

Mpox is a notifiable disease, and contact tracing will be undertaken by local Medical Officers of Health. Guidance regarding isolation and management of contacts is regularly updated as new evidence emerges in the Communicable Disease Control Manual available on the Manatū Hauora website.[[3]]

Currently, cases are required to isolate for a minimum of 7 days from the start of skin lesions and have a staged release from isolation dependent on meeting clinical criteria. During staged de-isolation, cases may return to most normal activities while lesions are covered, but they must continue to avoid contacts at high risk of serious disease and high-risk sexual and intimate activities. The full release from isolation requires clinician confirmation that all lesions have healed. As semen may still contain MPXV, cases must use condoms for a further 3 months.[[3]]

Contacts are not required to isolate but are advised to monitor for symptoms for 21 days from the date of last exposure. If contacts develop symptoms, they should inform their GP or sexual health clinician, and if lesions are present and/or they have proctitis they should be tested for mpox.

Prevention

Globally the incidence of mpox has been declining since mid-August 2022.[[1]] This downward trend is believed to have resulted from a combination of effective public health measures, vaccine-related immunity, natural immunity, and behavioural changes from the affected community.[[25]]

The Burnett Foundation Aotearoa and other partner organisations have been instrumental in raising awareness of mpox in the MSM communities in New Zealand, as well as in advocating for urgent action to prevent the escalation of mpox in New Zealand, including vaccine procurement and delivery.[[26]]

Specific vaccines have not been developed to prevent mpox. Smallpox vaccines do provide cross-protection against mpox infection and are thought to be at least 85% effective at preventing mpox infection, based on study data from Africa in the 1980s.[[27]] Vaccines can be used as primary preventive (pre-exposure) vaccination (PPV) to prevent infection or as post-exposure preventive vaccination (PEPV) for up to 4 days to abort an episode of active infection. PEPV has also been used between 4–14 days post-exposure and may result in mpox infection with milder symptoms.

The main vaccine used internationally is the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine. It contains a live attenuated non-replicating orthopoxvirus. It is marketed as JYNNEOS® (US), IMAVNEX® (EU), and IMVAMUNE® (Canada). This vaccine has fewer side effects than the earlier second-generation vaccines and can be used in immunocompromised individuals. It is traditionally administered subcutaneously with two doses, four weeks apart.

Side effects of the MVA-BN vaccine include pain at the site of injection (85%); redness, swelling, itching, and induration at the site of injection (40–60%); fatigue, muscle pain, and headaches (20–40%); nausea (17%), chills (10%) and fever (2%).[[28]]

There were no vaccine effectiveness studies prior to the release of the MVA-BN vaccine but antibody responses and preclinical studies showed it is effective when given pre-exposure. Early evidence from the US has shown that a single dose, given 2 or more weeks before exposure is protective among males aged 18–49. Unvaccinated individuals had a 14 times higher incidence of mpox incidence.[[29]]

There is also evidence that intradermal use induces a similar immune response to subcutaneous administration. The intradermal dose requires only one-fifth of the subcutaneous dose and hence it has the advantage of providing doses for more individuals at risk at a time of global and local vaccine shortage.[[30]] It has an increased rate of local adverse events including redness and itch compared with subcutaneous administration and should be avoided in those with immunocompromise, a history of severe keloid, and in children.

At present, it is the role of sexual health services and public health units to advise individuals about the risks and benefits of vaccination against mpox.

Conclusion

Based on global trends,[[1]] New Zealand is likely to see low levels of local transmission and imported cases of mpox amongst unvaccinated MSM at risk. Cases may also occur infrequently in other population groups. Clinicians have a central role in managing the outbreak through prompt recognition of cases, appropriate testing, and coordination with public health units. Clinicians working in different healthcare settings need to be aware of the wide variety of presentations, particularly recognising the atypical presentations, such as single lesions, proctitis, tonsillitis, and ophthalmic manifestations in high-risk individuals. Taking lessons from the early HIV pandemic, it is important to remove any barriers to individuals seeking care for mpox and clinicians wishing to offer wider testing, and it is important that individuals with suspected or confirmed mpox are treated without stigma or discrimination. In contrast to the emergence of HIV, effective public health interventions are already recognised and rapid diagnostic testing, antiviral treatments and effective vaccines are all available to swiftly control, and eventually eliminate transmission of this re-emerging infectious disease.