The origin of monkeypox outbreaks in non-endemic countries

In a recent review published on the OSF* preprint server, the author explained the mysterious origin causes of recent monkeypox outbreaks in non-endemic countries outside of Africa.

Study: The origin of the mysterious multi-country monkeypox epidemic in non-endemic countries. Image Credit: FOTOGRIN/Shutterstock


Cases of monkeypox are on the rise in several non-endemic countries around the world despite the lack of travel links and connected clusters with Africa. Despite the worldwide prevalence, the causes of origin of monkeypox beyond the African continent are unclear. If the much more deadly Ebola virus emerges in the same way, serious consequences for human health could be expected and, therefore, the origin of the mysterious outbreaks of monkeypox must be understood.

In this review, researchers reported the causes behind monkeypox outbreaks in several non-endemic countries around the world.

Pathological manifestations of monkeypox infections do not require transmission of monkeypox virus to other organisms

The recent outbreaks of monkeypox cannot be explained on the basis of logical conclusions from data obtained by experimental analysis, but by illustrating reality and making logical inferences only to obtain consequences which must agree with the experiments.

The effects of causative pathogens that allow immune pathways to protect organisms from acquiring infections by these pathogens do not depend on the exclusive nature of a certain pathogen, but on the immunological nature in which the pathogenic effects are shared with sterile cause effects.

Immunological mechanisms that decrease pathogen load in animals do not necessarily decrease disease severity or render disease asymptomatic. This is supported by lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) burdens reported in a few severe SARS-CoV-2 infections compared to asymptomatic and mild SARS-CoV-2 infections. The results indicate that the severity of a disease depends on the hyper-inflammatory state rather than the direct effects of pathogen toxicity.

Therefore, outbreaks of infections considered as asymptomatic do not necessarily require pathogen transmission but rather the disappearance of several conditions that allow immunological mechanisms to consider them as asymptomatic without eliminating the causes of the disease.

The manifestations of monkeypox in one case may not resemble other cases and may appear in the absence of the monkeypox virus

Different diseases with different causes but with pathological effects of identical immunology may present with different manifestations in the absence of the pathogen (monkeypox virus). Different causes with effects of the same immunological nature manifest themselves concomitantly in cases of monkeypox and are already present in individuals in non-endemic countries. Consequently, outbreaks of monkeypox have appeared in areas beyond the African continent, despite the lack of travel links and connected clusters with Africa.

Researchers have made tireless efforts to characterize the genetic basis for the widespread global prevalence of monkeypox in central parts of Africa compared to western parts of Africa. It has been assumed that the pathogens responsible for epidemics in Central Africa have higher transmissibility and virulence than those responsible for epidemics in West Africa.

However, a finding common to all clusters of monkeypox cases is exposure to disease-facilitating factors that allow immunological mechanisms to render monkeypox asymptomatic without eliminating etiological factors of the same immunological nature. Therefore, the origin of monkeypox in non-endemic areas does not depend on the transmissibility or virulence of the monkeypox virus but on the disappearance (and reappearance) of the conditions in response to which the manifestations of monkeypox arise.

Moreover, the manifestations of an infection linked to a particular pathogenic organism are as diverse as the disappearance of conditions which allow the immune system and different motor factors of the same immunology to give rise to concomitant asymptomatic infections. The severity of the manifestations is comparable to those of infections sharing the same immunology, regardless of the transmissibility and virulence of the pathogenic organism.

Pathogen-related manifestations would have catastrophic effects in individuals even in the absence of the causative pathogen if factors cause the disappearance of conditions that allow infections with the same immunology to be considered asymptomatic. Such infections could spread widely in a short time.


Based on the findings, further research needs to explore the immunological nature of the deadliest Ebola virus infections and identify different diseases that respectively share similar immunology with Ebola infection.

Such an approach would be more beneficial in preventing the likely catastrophic effects of Ebola virus infections than in studying the genetic basis of Ebola virus infections or the transmissibility and virulence of Ebola virus. Additionally, the factors that allow immunological mechanisms to consider Ebola virus infections as asymptomatic need to be determined.

*Important Notice

OSF publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

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