Diagnostic testing and disease surveillance are back in the spotlight as scientists and public health workers closely monitor the current outbreak of monkeypox that has emerged in cities across Europe, the US, Australia and Canada. While the disease is not easily contracted, and in most cases is not life-threatening, the epidemiology of this outbreak is different to that which has been seen previously. It has been suggested that lack of routine vaccination for smallpox after eradication of that disease in 1980 may have contributed to an increase in monkeypox cases in humans in recent decades.
Monkeypox virus was first discovered in 1958 and is known to be endemic in 12 countries in Africa, four of which have reported cases to the World Health Organization (WHO) in the period 15 December 2021 to 1 May 2022. There are two groups or “clades”, one found in the Congo Basin of Central Africa with a case fatality of up to 10%, and one in West Africa, with a case fatality of around 3%. Preliminary genomic sequence data from a patient in Portugal in the present outbreak showed the virus to belong to the less dangerous West African clade. In contrast to SARS-CoV-2, monkeypox is a DNA virus, a type of virus which is usually more stable with regard to mutations and evolution of new variants. There is no evidence to date that the monkeypox virus in this outbreak has fundamentally changed its composition relative to previously known viruses.
In the early clinical stages, monkeypox can appear similar to more common rash-causing diseases, such as chickenpox, but it can usually be differentiated because the monkeypox rash often extends to the palms of the hands and soles of the feet, which are spared in most other diseases. However, clinical presentations and severity may vary, and atypical presentations have been noted during this outbreak.
On 23 May 2022 the WHO issued interim guidance for laboratory testing for the monkeypox virus. Laboratory confirmation of monkeypox relies principally on nucleic acid amplification tests, such as PCR, performed on material from the skin lesion. Testing of other body fluids and tissues, including oropharyngeal swabs, urine, semen, rectal and/or genital swabs, may be indicated based on the clinical presentation and location of the lesions. However, data on the accuracy of testing on these samples is still limited.
While there are currently no commercially available PCR tests for monkeypox, a number of primer and probe sequence sets for PCR assays for monkeypox virus have been published and can be used for in-house assays in laboratories with appropriate capacities. Dedicated monkeypox tests, including the GeneXpert platform and recombinase polymerase amplification assay have been developed, although not yet commercially available.
While monkeypox is not easily transmissible and the present outbreak gives no cause for panic, its emergence underlines the need for sustained global surveillance systems that can detect emerging viruses in every country in the world. The focus on diagnostics for COVID-19 has boosted testing and surveillance capacity worldwide that can be useful for monkeypox, but dramatic inequities remain in low- and middle-income countries.
The monkeypox emergence has highlighted challenges faced by diagnostic developers that may have been hidden by the fast pace of innovation at the start of the COVID-19 pandemic. Test manufacturers have always struggled to respond to sporadic and unpredictable demand for outbreak diseases such as monkeypox. Ensuring that tests can be developed, made available and implemented quickly relies on access to well-characterized disease samples that can be used to validate new tests, clinical trial networks that can be activated to provide data for regulatory review, production lines standing ready, import and export systems being in place, and health workers being trained and ready to use the tests. All of these elements require investment, with little return on the horizon in the vast majority of cases. FIND’s efforts on the 100 Days Mission to respond to future pandemic threats seeks to address these challenges.
Daniel Bausch, Director of Emerging Threats and Global Health Security at FIND, will present an overview of available diagnostics and those in the pipeline as well discuss laboratory research needs at the upcoming WHO R&D Blueprint meeting Monkeypox research: What are the knowledge gaps and priority research questions? on 2 June 2022, 13:00–19:30 CEST. For more details and to register, please click here.