Monkeypox Outbreak in Non-Endemic Countries: A Cause for Concern?

Monkeypox is a viral disease of global public health importance, according to the World Health Organization (WHO). It was first discovered in 1958 after being isolated from monkeys by a team of Danish scientists, and the first case of infection in humans was reported in a child in the Democratic Republic of the Congo in 1970.

Infection with the monkeypox virus results in symptoms similar to smallpox, but less severe. The illness usually lasts for 2–4 weeks, beginning with symptoms such as headaches, muscle aches, swollen lymph nodes and fever. Once the fever appears, 1–3 days later a rash develops, which progresses through several stages before forming scabs that eventually fall off.

Monkeypox is a primarily zoonotic disease endemic to countries in Central and West Africa such as the Democratic Republic of the Congo, Cameroon and the Central African Republic. Most cases are acquired through contact with an infected animal, though the exact route of transmission is yet to be determined. The rare monkeypox cases that do occur in non-endemic areas are typically linked to travel to endemic countries. However, in 2022 many cases with no direct link to travel have been confirmed in 12 non-endemic WHO member states, such as the United Kingdom, Spain, Portugal and the United States*. According to the WHO, this outbreak “represents a highly unusual event”.

To find out more about this monkeypox outbreak, Technology Networks spoke to Dr. Jake Dunning, senior researcher in emerging and high consequence infectious diseases at the University of Oxford, and Prof. Piero Olliaro, director of science at the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC).

Technology Networks also spoke to Dr. Dennis Hruby, chief scientific officer at SIGA Technologies, a health security biotechnology company that has developed the antiviral drug TPOXX® (tecovirimat), which has been approved for the treatment of monkeypox in the EU and for compassionate use in the UK.

Sarah Whelan (SW): How does monkeypox spread and how infectious is it?

Dr. Jake Dunning (JD): Existing research suggests that monkeypox does not spread very easily between people and that close contact is required.

The virus can be found in respiratory droplets, and it’s believed that some of the human-to-human transmission occurs through exposure to these droplets, probably with close-range (face-to-face) contact being required over a sustained period (possibly a few hours). We also know that direct skin-to-skin contact with an infected person, or virus that has come from an infected person – such as from shed lesions, scabs and skin particles – may be a source of infection. The amount of virus produced this way can be quite high and indirect transmission through exposure to contaminated materials such as bedding may also lead to infection.

Skin-to-skin, or perhaps skin-to-lesion exposure, may be more important in the outbreaks we are seeing now outside Africa, particularly where early data suggest close physical contact, including sex, may be playing a part. This is supported by early reports from clinicians that some patients have a preponderance of lesions, or more severe lesions, on the genitals or other areas of the body that may have been directly exposed to infected lesions during sex. It is important that data are collected to confirm or refute these ideas, and we need much more multidisciplinary research into transmission. It seems likely that different routes and modes of transmission occur, and that the relative contribution of any one mode or route may differ depending on the context and circumstances of the interaction, whether that is with an infected human or an infected animal.

SW: Monkeypox is rare and usually associated with travel to endemic areas such as West and Central Africa ‒ why do you think we are now seeing unusual levels of transmission in other areas such as Europe and North America?

JD: Monkeypox may be considered a rare travel-associated infection, with occasional and limited secondary transmission in countries outside of Africa, but it is an increasingly common and problematic infectious disease in some countries in West and Central Africa. The research and investigations into the May 2022 outbreaks in Europe and North America are in their infancy and it is important that we look at findings based on actual, reliable data. However, it is reasonable to hypothesize that an individual or individuals initially caught monkeypox through travel-associated exposure (linked to affected countries in Africa), and then there was an opportunity for this infection to start spreading among people who share something in common, through close physical contact. Such common, shared features could be attendance at the same events or places where the conditions for close physical contact are present, or it may include sex between people who identify sexually in the same way. Basically, the virus may have been introduced into a new population or subpopulation or group with shared common characteristics and activities and benefited from opportunities for transmission through close physical contact. This is a really important area for research so that we can understand conditions for transmission and help protect people who may be at increased risk of infection, wherever they may live in the world.

Monkeypox is capable of infecting anyone if they are exposed and do not have immunity; it does not single out or target one group, for example, because they are men who have sex with men.

It’s also important to remember that the greatest burden of monkeypox to date has occurred in African countries; greater research efforts, capacity building and assistance with improving healthcare infrastructure generally cannot be ignored with this global health problem.

SW: Are there vaccines available that are effective against the monkeypox virus?

Prof. Piero Olliaro (PO): Research shows that immunity against smallpox, whether naturally acquired or through previous vaccination programs that led to its eradication, cross-protects against other infections caused by members of the Orthopoxvirus genus, including monkeypox. However, protection likely wanes with the passing of time, as indicated by the general trend for cases in endemic countries to get younger in recent years. The newer vaccines that have been developed, which are much easier to administer and have far fewer side effects than the old vaccines, generate good levels of antibodies in healthy human studies and demonstrate protection in animal models of monkeypox – but, apart from correlates of protection, definitive evidence from clinical trials in humans is not available, a limitation shared with therapeutics. Research should now focus on looking at what vaccination strategies should be considered in which context, not only in Western countries, but also importantly in countries where monkeypox has been a bigger problem for much longer.

While large-scale vaccination programs will likely be challenging and possibly not cost-effective in most settings, one could consider identifying groups at risk of infection or complications and then offer vaccination to those people before they are exposed.

When it comes to post-exposure prophylaxis in exposed persons, we don’t know if these vaccines are an option in practice. This is because if you start adding the time it takes to diagnose the “index case”, to identify and trace their contacts, and for the vaccine to elicit a protective immune response, the infection might have already occurred.  At the same time, we can’t exclude that vaccines might help to reduce the severity of illness if the person does get infected, but this too will require confirmation. There might be alternative options, such as combining an antiviral (to cover this gap) and a vaccine (for longer-term protection), but this might be speculative, as it would require clinical trials, and yet much would depend on the prices of products and cost-effectiveness of the intervention.

Again, let’s not forget that the greatest need for research and access to vaccines and treatment is in affected countries in Africa, although we must also seize opportunities to conduct studies in other countries and regions where outbreaks are occurring now, for the benefit of all.

SW: Could vaccinations become a necessary measure to protect the public against monkeypox?

PO: It seems that, at this stage, the main public health concern in non-endemic countries is to break chains of transmission to prevent it from becoming established. Vaccination alone cannot achieve this. Ideally, we would make decisions on more research to identify at-risk groups, evaluate different vaccination strategies and social and behavioral factors that may influence the success of vaccination programs, but the window of opportunity to intervene may be too narrow to build the evidence base. Currently, it is early days in the countries seeing larger outbreaks for the first time so it’s too soon to say whether monkeypox is going to be an established problem in these countries and one that may benefit from vaccinating large numbers of people. I understand that a number of countries are purchasing vaccines, but I don’t know if there is already a clear strategy as to how to use them.

Attention given to these cases that we are seeing in Western countries should not detract attention from the fact that it’s essential to concentrate research efforts on understanding monkeypox and how to prevent it and treat it in countries with the greatest burden and endemic or enzootic risk. Considering that these countries are low- or middle-income, there must be equitable access to research and opportunities to conduct studies, as well as benefiting from identified interventions to treat and prevent monkeypox.

SW: How serious is infection with monkeypox, and what treatments are available?

Dennis Hruby (DH): Monkeypox infections can range from mild to serious infections with hundreds of lesions, to life-threatening. Historically, in Africa death rates have ranged from 1‒10% depending on which strain one is infected with. Current standard of care is supportive therapy and isolation. Tecovirimat is approved for the treatment of monkeypox in humans by the European Medicines Agency (EMA). Based on animal data and use in humans under compassionate use protocols, it is expected to be effective.

SW: Could you tell us more about the antiviral drug TPOXX (tecovirimat)?

DH: TPOXX is an orally bioavailable small molecule. It works as an egress inhibitor, trapping infectious virions within infected cells until the host’s immune system can clear the infection. It has been shown to be effective in preventing morbidity and mortality in a number of animal models and had an excellent safety profile in human clinical trials. It is a very stable drug with a shelf life of seven years at controlled room temperature for the final drug product.  Its development was in partnership with the United States Government and 1.7 million courses are stockpiled and maintained in the Strategic National Stockpile. Regulatory approval for the use of TPOXX to treat symptomatic smallpox was received by the FDA in 2018 and Health Canada in 2021.  Regulatory approval by the EMA for the treatment of orthopoxviral diseases, including monkeypox, was received in 2022.

Dr. Jake Dunning, Prof. Piero Olliaro and Dr. Dennis Hruby were speaking to Sarah Whelan, Science Writer for Technology Networks.

* Data correct as of May 21, 2022