Emerging Infectious Diseases
Mpox disease (formerly known as monkeypox disease) is a viral zoonotic disease caused by the mpox virus; a member of the Orthopoxvirus genus that also includes variola virus, the causative agent of smallpox. The mpox virus has two distinct genetic clades – Clade I (previously called the Congo Basin (central African) clade and Clade II (the west African clade), the former being more transmissible and causing more severe disease.
With the eradication of smallpox, mpox disease has emerged as the orthopoxvirus of global public health importance. The virus is predominately found in sub-Saharan Africa but spread to non-endemic countries in 2022, particularly the Americas and Europe, with more than 86 000 confirmed cases and 116 deaths as of April 2023. This recent clade IIb outbreak, primarily affecting men who have sex with men (MSM), represents the first occurrence of laboratory-confirmed cases and sustained transmission reported in countries without direct or immediate epidemiological links to the endemic West or Central Africa.
It is usually a self-limiting disease characterised by fever, headache, lymphadenopathy and skin lesions. Most infected persons recover within a few weeks without the need for treatment. However, the disease can be severe among advanced (CD4 count <350 cells/mm3) or untreated HIV infection, young children and pregnant women leading to bronchopneumonia, sepsis, encephalitis, and keratitis with ensuing loss of vision.
There is no approved specific therapy for mpox. Clinical management is primarily targeted at alleviating symptoms, managing complications, and preventing long-term consequences. It has been shown that prior immunization with smallpox vaccines has a protective effect against mpox virus and improves clinical manifestations of the disease.
Detection of mpox viral DNA by PCR using skin lesion samples or a biopsy where feasible is the preferred diagnostic method given its high specificity and sensitivity. PCR blood tests are often inconclusive due to a short viraemia phase of infection in relation to timing of sample collection. Thus, limiting the use of blood specimen in the diagnosis of mpox. Orthopoxviruses are serologically cross-reactive, therefore, serological and antigen detection methods do not provide mpox-specific confirmation or distinguish active infection from prior smallpox vaccinations or other orthopoxvirus infections. As such, these tests are not recommended for use in resource-limited settings. The development of affordable, rapid mpox-specific serology and IgM assays is critical to enable a quick response during outbreaks.
Currently, two vaccines – both based on a live vaccinia virus – are available for use among high-risk adults. These are third generation JYNNEOS, a two-dose vaccine approved by US FDA in 2019 and a second-generation smallpox vaccine – ACAM2000. However, availability for both remains limited. ACAM2000’s use may be associated with unintended disease transmission, serious adverse events and is contraindicated in immunocompromised persons including populations that are at increased risk of unrecognized HIV infection. Thus, making it an unattractive option for use among high-risk populations for mpox disease. Higher generation (4th) mpox vaccines are being explored but these are still in early phase of development.
Therapeutics developed and approved for other poxviruses (mainly smallpox) have typically been repurposed and recommended for use by WHO during outbreaks. Recently, a repurposed antiviral agent, tecovirimat, has been licensed by the European Medicines Agency for mpox disease based on animal and small human safety studies. Chimerix’s Brincidofovir has also completed Phase III trials. However, these drugs are not widely available and large efficacy trials for mpox are still lacking. The recent 2022 outbreak has seen the proliferation of several preclinical and clinical candidates specifically targeted at mpox virus, with most candidates still in early development. Vaccinia immune globulin is the only biologic available and FDA-approved for vaccinia virus in adults and children. However, its use for mpox disease is under the US FDA’s expanded access protocol for orthopoxviruses through the US CDC. While a formal consensus is yet to be reached, WHO has published a draft target product profile (TPP) for mpox therapeutics highlighting the need for a stable, once daily/weekly oral or parenteral formulation effective against all stages of infection. Combination therapy for high-risk groups and antivirals as post exposure prophylaxis (PEP) among close contacts is being considered, for which a separate TPP for PEP has been suggested by WHO’s working group.
Seegene Inc’s Novaplex MPXV Assay, a real-time polymerase chain reaction (PCR) diagnostic kit, proved 100% specificity and 100% sensitivity in clinical evaluation conducted in Israel. The novel test specifically detects the mpox virus target gene and provides results in 90 minutes.