Mpox transmission and control: Understanding the virus and global response

02 Oct 2024

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Mpox is a vaccine-preventable zoonotic disease that also infects humans. It was originally identified in 1958 in research monkeys, earning the name Monkeypox, which was subsequently changed to mpox in 2022. The first human case of mpox was identified in what is now known as the Democratic Republic of Congo in 1970, and since then been most commonly found in the African continent. Mpox has only recently become a global health issue, with global transmission and an increase in cases resulting in two WHO Public Health Emergency of International Concern (PHEIC) declarations, in 2022 and 2024.

The virus

Mpox is a double stranded DNA virus, from the family poxviridae and genus orthopoxvirus, the same as smallpox (variola virus). (Figure 1). Some of the similarities between smallpox and mpox and will become evident in this article, and explained by belonging to the same family.

Figure 1. Taxonomy of smallpox and mpox. Source: Clinical Manifestation, Transmission, Pathogenesis, and Diagnosis of mpox Virus: A Comprehensive Review

Transmission

Although the historical name, monkeypox, leads you to believe monkeys as the natural host (reservoir) of mpox, the reservoir for mpox is not known, although thought to include small mammals.

Historically, mpox transmission has been primarily animal-to-human, with human-to-human transmission occurring subsequently within households. However outbreak investigations from the 1980s identified a greater increase in cases due to human-to-human transmission, with prolonged community transmission occurring for the first time in 1996 (Figure 2).1

Transmission of mpox occurs through multiple routes, although predominantly through direct and close contact. Transmission can occur when a person comes into contact with an infected human, animal or contaminated material.2

Transmission occurs through broken skin or mucous membranes e.g. respiratory tract, nose, mouth, genitalia and can occur through contact with infectious material from skin lesions of an infected person, Respiratory droplets during prolonged face-to-face contact or fomites.2

1 S2.0 S1198743X23003890 Gr1

Figure 2. Transmission of mpox. Source: Emergence of mpox in the post-smallpox era

Epidemiology

Two clades of Mpox have been identified: clade I and clade II. Within each clade, two subclades have been identified, subclade Ia and Ib and IIa and IIb. Clade I, previously known as the Congo Basin, has historically been found in five countries in Central Africa, particularly northern and central regions of the Democratic Republic of Congo.3,4 Clade II, previously known as the West African clade, has traditionally been found in West Africa. Mpox cases have been reported since 1970, presumed primarily due to zoonotic transmission.3 Clade Ib was only recently discovered in 2023.5

Outbreaks of mpox Clade I regularly occur in Cameroon, Central African Republic, the Democratic Republic of Congo and sporadically in other countries.3 In 2003, the United States of America reported an outbreak of mpox, with all confirmed cases linked to prairie dogs. The dogs were infected after being housed near imported small mammals from Ghana. This outbreak was the first reported cases of mpox outside of Africa.6

Prior to 2018, few mpox cases were detected outside of Central Africa; however, this has significantly changed since 2022. In 2022, a clade IIb outbreak led to a PHEIC declaration by the World Health Organization (WHO). The outbreak was predominantly driven by sexual transmission between men who have sex with men.3 The PHEIC was stood down in 2023; however, cases continue to be reported globally (Figure 3). On 14 August 2024, a PHEIC was declared by the WHO due to the discovery and rapid spread of clade Ib in the Democratic Republic of Congo and neighbouring countries, as well as an increasing number of countries in Africa reporting clades Ia and II.5

Figure 3. Geographic distribution of mpox by clade, 1 January 2022 - 29 September 2024. Source: 2022-24 Mpox (Monkeypox) Outbreak: Global Trends

Globally, from 1 Jan 2022 – 31 August 2024, 106 310 laboratory confirmed cases of mpox and 234 deaths have been reported in 123 countries.7 In August 2024, 48 countries reported cases with 33 reporting an increase in cases and one country reporting their first case(Figure 4).7 Australia’s first case of mpox was detected in 2022. As of 7 September 2024, 957 cases have been detected across Australia since 2022, 787 in 2024. 8

Global Map 1

Figure 4. Geographic distribution of mpox by clade, 1 January 2022 - 22 September 2024. Source: 2022-24 Mpox (Monkeypox) Outbreak: Global Trends

The definitive cause of the global spread of mpox has not been identified; however, numerous reasons for the resurgence have been suggested:9-12

  • Waning immunity to poxviruses in those who are vaccinated in earlier smallpox vaccine campaigns in the middle of the 20th century
  • Large unvaccinated population, since smallpox vaccination ceased in 1980
  • Changes in social and environmental factors
  • Surveillance, control, treatment and vaccination availability

2024 Mpox outbreak

From 1 January 2024 – 30 September 2024, there have been 34 297 cases of mpox (all persons who have presented with symptoms consistent with the suspected case definition for mpox) of which 6806 are confirmed cases, and 866 deaths have been reported from 15 countries in Africa.13 Of these, multiple countries in Africa have reported their first mpox case in 2024.7 In comparison, all 2023 cases identified by the African CDC were from seven countries in Africa .13

In the week between 15-21 September, there were 2490 new cases and 26 deaths reported from ten countries in Africa.13 Rates of infection in children are high, with rates in children under 15 years old currently between 38% and 60% (29% in children under 10 years old) in some countries.13

The current outbreak affecting the eastern Democratic Republic of Congo and neighbouring countries is mostly affecting adults and spreading predominantly through sexual contact – this is linked to the new clade, clade 1b.14 In areas of the Democratic Republic of Congo where mpox is endemic, mpox is mainly affecting children and spreading in multiple ways – linked to clade 1a.14 Historically, clade I has been more transmissible, caused more severe illness, and had a higher case fatality ratio than clade II. Reported mortality rates for Clade I range from 1% to 10%.15 The current case fatality rate reported by African CDC is 2.52%.13

Historically, clade I transmission occurred through animal-to-human contact, and outbreaks was not sustained. However, in the current outbreak, transmission is occurring among household contacts and through both heterosexual and same-sex sexual contact.15-16 Children are being infected through animal or household contact and are experiencing more severe disease than adults.15

PHEIC declaration

The International Health Regulations (2005) (IHR) aim to aid in the prevention and response to acute public health risks that have the potential to cross borders and affect people worldwide.17

Under the IHR, a PHEIC is defined as “an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response”.17 

Situations covered under a PHEIC17 include:

  • Is the public health impact of the event serious?
  • Is the event unusual or unexpected?
  • Is there a significant risk of international spread?
  • Is there a significant risk of international travel or trade restrictions?

If two out of four criteria are met, a PHEIC is declared.

Clinical presentation

The incubation period (period of time between exposure to the virus and displaying symptoms) for mpox ranges from 5-21 days, with invasive exposure (contact with broken skin or mucous membranes) having a shorter incubation period than non-invasive exposure.2

The infectious period (period when a person can spread the disease) for mpox commences with symptom onset, resolving once the rash has resolved, scabs formed and fallen. Prior to the onset of symptoms, cases are not considered infectious.

Fever, swollen lymph nodes (lymphadenopathy) and a centrifugal rash developing after the onset of fever are the classical presentation of mpox, with other symptoms including headache, muscle ache, joint pain and fatigue (Figure 5).2,18  Although not all individuals present with these symptoms, during the Clade 2b outbreak in 2022, only 56% of cases presented with lymphadenopathy, and 64% of cases had 10 lesions or less.19 Complications of mpox include secondary infection, sepsis, pneumonia and encephalitis, with increased risk in immunocompromised individuals, young children and pregnant women.

Monkeypox Rash Lesions Image 6 1ed

Figure 5. Mpox lesion. Source: UK Health Sercurity Agency

Diagnostic testing

Polymerase Chain Reaction (PCR) is the preferred laboratory diagnostic method for mpox. Specimens are collected from the skin lesion (skin, fluid, crusts) for swabbing. If no skin lesions are present, oropharyngeal (from the mouth) or rectal swabs can be collected, although a negative result does not rule out mpox infection.20

Management

Currently there is no treatment specifically for mpox. Mpox is generally a self-limiting infection. For cases of uncomplicated mpox, management is supportive, with fluids and pain relief. For cases of severe mpox, those at risk of severe infection, or those with complications, Tecovirimat (a medication developed to treat smallpox) is recommended at a dose of 600mg twice daily for 14 days. If unavailable vaccinia immunoglobulin is an alternative or can be used in combination if an individual is severely unwell.21,22

Tecovirimat is an antiviral medication that was approved in 2018 by the United States Food and Drug Administration, as the first treatment for smallpox. Tecovirimat is efficacious as post-exposure prophylaxis (PEP) (after exposure to the virus) and treatment in animals with orthopoxviruses inclusive of mpox.23 The Therapeutic Goods Administration has granted an emergency exemption for the use of Tecovirimat in Australia for mpox.22

Treatment guidelines for mpox can be found here.

Public health response

Vaccination

Three vaccines are effective for smallpox, MVA-BN, LC16m8 and ACAM2000. They can also be used for the prevention of mpox. The primary vaccine course is 2 doses at least 28 days apart. A booster dose is not recommended, including for those who are immunocompromised.24

Pre-exposure prophylaxis

An mpox vaccine can be used as pre-exposure prophylaxis (to prevent infection) and recommended for those at high risk, especially during an outbreak.25

  • health and care workers at risk of exposure;
  • people in the same household or close community as someone who has mpox, including children;
  • people who have multiple sex partners, including men who have sex with men; and
  • sex workers of any gender and their clients.
Post-exposure prophylaxis

An mpox vaccine can be administered to individuals who have been in contact with someone who is infected with mpox. Vaccines should be given within 4 days after contact with someone with mpox and can be given for up to 14 days after contact, if the person has not developed symptoms.25

Further information on post-exposure vaccination can be found in the Australian Immunisation Handbook.26

Prevention

In the current outbreak setting of mpox, prevention is focused on avoiding close contact with people who have suspected or confirmed mpox.

The WHO25 recommends:

  • If someone you know is diagnosed with or has suspected mpox, avoid close contact with them, including sexual contact
  • Know the symptoms and check yourself regularly
  • If you have symptoms, seek health advice and self-isolate while you wait to get tested
  • Get vaccinated if it is available to you
  • Clean and disinfect environments that could have been contaminated with the virus from someone who is infectious
  • Stay informed about mpox in your area
  • Have open, non-judgmental conversations with people you come into close contact with (especially sexual contact) about any symptoms you or they may have.

During the 2022 mpox outbreak, multiple mpox campaigns were undertaken globally and in Australian to prevent the spread of mpox. The current mpox outbreak is being seen in some countries for the first time, with transmission occurring not only through sexual contact. Therefore it is important for health promotion messaging to cover all methods of close contact transmission and is provided in countries seeing mpox for the first time.

Protect Yourself And Others From Monkeypox

Figure 6. Public health advice on protecting yourself and others from mpox. Source: World Health Organization

Global public health response

Following the 2022 mpox outbreak and resulting standing down of the PHEIC, Standing recommendations for mpox were issued by the Director-General of WHO.27 The Strategic framework for enhancing prevention and control of mpox 2024-2027 was released in May 2024 to achieve and sustain the elimination of human-to-human transmission of mpox, implemented through the core WHO Health Emergency, Preparedness and Response framework.28 Since the recent PHEIC declaration, a Global strategic preparedness and response plan for Sept 2024 to Feb 2025 has been released for the prevention and control of mpox.29 The response strategy29 aims to:

  • strengthen surveillance and detection
  • enhance community protection
  • safe and scalable care
  • equitable access to medical countermeasures and
  • emergency coordination

Globally there is a vaccine shortage and limited supply. On 31 August 2024, in collaboration with partners, the United Nations Children’s Fund issued an emergency tender for the procurement of mpox vaccines.30 The tender has been issued to secure vaccines for the worst-affected countries and will establish conditional supply arrangement with manufacturers. The collaboration with partners also includes working to facilitate vaccine donations from existing stockpiles in high-income countries. The tender has resulted in UNICEF securing MVA-BN mpox vaccine, ensuring access for 77 low and lower-middle income countries.31

In addition to the issuance of Temporary Recommendations32, the declaration of a PHEIC is a global alert to prepare and respond. The declaration of a PHEIC in 2022 was able to control the clade II outbreak; however, transmission remains. With ongoing clade II transmission globally and outbreaks of clade I and II spreading through Africa and to vulnerable populations, it is hoped that with the declaration and subsequent coordination and response from both affected countries and the global community, the current mpox outbreak will be contained.

The information provided is for informational purposes only. The global mpox outbreak is evolving rapidly, and it is essential to stay informed by consulting the latest updates on epidemiology, transmission, management, and prevention.

References
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