Letter to the Editor
Between 1st January 2022 and 13th March 2023, the World Health Organization (WHO) received reports from 110 countries spanning all six WHO regions, indicating a cumulative total of 86,496 laboratory-confirmed cases of mpox and 111 associated deaths. In non-endemic countries, the largest monkeypox (mpox) virus epidemic was first detected in May 2022. Mpox, a viral zoonosis, was found to be still on the rise [1,2].
“Spillover” probably caused monkeypox to spread to people. The virus could hypothetically spread to a new permissive host with a wider global distribution; climate change presents a risk to humans. Spillover was anticipated to follow the cryptic distribution. The genetically created virus is still spreading quickly (MSSE). When a naturally existing zoonotic virus—such as avian influenza into a human host, human-to-human transmission is typically impossible or unsustainable. However, if the virus acquires enough of the correct mutations, such a form of transmission is possible. As was already mentioned, it is well known that the mpox strain that will cause the outbreak in 2022 has a unique genetic structure [3].
Arthropod-borne infections are spread by biting infected arthropods like ticks and mosquitoes. These infections are a huge concern around the globe, and viruses, in particular, pose a serious risk to the general public's health. We attempt to explain how complicated interactions between viruses, vectors, and humans can cause an epidemic to spread based on demographic, ecological, and economic aspects as well as human activity (Fig. 1). Genetic changes can potentially affect the risk of arthropod-borne viruses (arboviruses) transmission. For example, the strain of chikungunya virus (CHIKV) that is spread by the Aedes aegypti mosquito vector developed a mutation in the E1 envelope glycoprotein during the pandemic of 2005–2006 in the Indian Ocean region. This mutation made it easier for the virus to spread in humans. An important antiviral defense mechanism in arthropods is the RNA interference (RNAi) pathway, which emphasizes that an arbovirus's ability to successfully defeat this RNA-based immune response dictates its potential to replicate in specific vectors. It could be worthwhile to consider whether insects are a part of mpox's normal life cycle. The seropositivity for mpox antibodies found in Petrodromus tetradactylus (four-toed elephant-shrew) raises the possibility that insects play a part in mpox's natural lifetime. The fact that mpox antibodies are found in so many different species and that samples from Funisciurus sp., Cricetomys sp., and Graphiurus sp. showed evidence of virus infection suggests that the natural lifecycle is a complicated interplay between reservoir hosts and accidental species. Arthropod transmission should be considered in the mpox outbreak of 2022.
Fig. 1.
The disease triangle of mpox virus. Human mpox is a zoonotic infection with a disease triangle: the reservoir, the host, and the vector, respectively. According to the definition, the disease triangle is a conceptual model that shows the interactions between the environment, the host, and an infectious agent.
Furthermore, it has been found that the 2022 monkeypox virus exhibits a strong mutation bias, which is most likely a sign that the apolipoprotein B mRNA editing catalytic polypeptide-like 3 (APOBEC3) enzyme is likely involved in the editing of the viral genome. Additionally, there is a known mutation in the mpox immunogenic surface glycoprotein B21. The earliest signs of microevolution within the virus that would cause the pandemic in 2022 can also be seen in 15 SNPs, which have been proven to exhibit the same mutation bias as that previously described during human-to-human transmission. Events involving gradual gene loss are thought to have served as a catalyst for the evolution of pox viruses. This has led to the theory that identifying a sub-cluster of two sequences in the 2022 monkeypox virus that shares a 913bp frameshift deletion in a gene coding for an Ankyrin/Host range protein is linked to adaptation to human-to-human transmission.
Arthropods transmit a wide range of diseases worldwide. Vector-borne diseases are those that are spread by arthropods. In general, vector-borne diseases are human diseases caused by pathogens such as viruses, parasites, bacteria, and protozoa. Some arthropods including mosquitoes, ticks, sandflies, blackflies, mites, fleas, tsetse flies, lice, and triatomine bugs can transmit diseases to humans and animals. Some arthropods such as mosquitoes, ticks, sandflies, blackflies, mites, and fleas have been naturally feeding on reservoirs of the mpox including humans, monkeys, anteaters, hedgehogs, prairie dogs, squirrels, and shrews. However, the arthropods may have played an important role in the secondary transmission and reservoir of mpox. The natural mpox lifecycle may be a complex interaction of reservoir hosts and arthropod species as incidental vectors and reservoirs of mpox. Most questions about understanding mpox transmission routes have hypothetical answers that can only be confirmed or refuted by further investigation [4].
Jezek et al. investigated mpox transmission from infected squirrel tissue to other naive squirrels by ants and found no evidence of transmission [5]. Although, Petrodromus tetradactylus, an insectivore that consumes little plant material but is seropositive for OPV antibodies, suggests that the role of insects in mpox's natural lifecycle is worth investigating. The presence of mpox antibodies in so many different species, as well as virus detection in Funisciurus sp., Cricetomys sp., and Graphiurus sp., indicate that the natural lifecycle is a complex interaction of reservoir hosts and incidental species. However, one of the poxviruses has been transmitted by arthropods. Lumpy skin disease (LSD) is a vector-borne viral disease that affects cattle and wild ruminants. It is caused by the lumpy skin disease virus (LSDV), which belongs to the genus Capripoxvirus and the family Poxviridae. This viral disease can be transmitted by arthropods such as mosquitoes and ticks. LSDV has been detected in a number of countries, including Africa, the Middle East, Europe, and Asia. There is still uncertainty about the mpox virus natural history, and further research is required to identify the exact reservoir or vector and understand how the virus circulates in the wild. In the case of mpox, it is unclear whether or not arthropods might act as an effective means of transmitting the virus to humans. Research and related investigations should be conducted to better understand the various transmission routes used by arthropod.
At the end of this new idea, research is needed to better understand the transmission routes of the mpox virus, which is already affecting multiple continents and may be spreading through new channels during the COVID-19 pandemic.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Ethics approval
Not applicable.
Consent to participate
Not applicable.
Consent to publish
Not applicable.
CRediT authorship contribution statement
Ismaeil Alizadeh: Conceptualization, Writing – original draft. Maryam Shafaati: Writing – original draft. Milad Zandi: Conceptualization, Data curation, Writing – review & editing.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Handling Editor: Patricia Schlagenhauf
References
- 1.Zandi M., Shafaati M., Hosseini F. Mechanisms of immune evasion of monkeypox virus. Front Microbiol. 2023 Feb 1;14:160. doi: 10.3389/fmicb.2023.1106247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Shafaati M., Zandi M. Monkeypox virus neurological manifestations in comparison to other orthopoxviruses. Trav Med Infect Dis. 2022;49 doi: 10.1016/j.tmaid.2022.102414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Scholthof K.-B.G. The disease triangle: pathogens, the environment and society. Nat Rev Microbiol. 2007;5(2):152–156. doi: 10.1038/nrmicro1596. [DOI] [PubMed] [Google Scholar]
- 4.Shafaati M., Zandi M. State-of-the-art on monkeypox virus: an emerging zoonotic disease. Infection. 2022 Dec;50(6):1425–1430. doi: 10.1007/s15010-022-01935-3. [DOI] [PubMed] [Google Scholar]
- 5.Jezek Z., Marennikova S., Mutumbo M., Nakano J., Paluku K., Szczeniowski M. Human monkeypox: a study of 2,510 contacts of 214 patients. J Infect Dis. 1986;154(4):551–555. doi: 10.1093/infdis/154.4.551. [DOI] [PubMed] [Google Scholar]