Mpox: A re-emerging zoonotic viral disease
Das T 1*, Das NK2 and M. Sahoo1
1ICAR-NIFMD-ICFMD, Bhubaneswar
2BVO, Bisoi, Mayurbhanj, FARD, Government of Odisha
*Corresponding author E mail id: tarenisahoo@gmail.com
Monkeypox/ mpox is a viral zoonotic disease. There are two genetic clades i.e. Central African clade (Clade I) and West African clade (IIa & IIb) mpox virus. The West African clades are less lethal than central African clades. Due to discontinuance of small pox vaccination after its eradication in 1970s, the MPXV incidences have increased. Growing contacts between humans and small mammals due to deforestation, climate change, civil war, demographic changes, migration etc. has augmented mpox incidences. The suspected and confirmed cases of mpox were also detected in different states and UT of India like Kerala, Delhi, Uttar Pradesh, Bihar and Telangana. In India, 30 cases of mpox have been reported since July 2022. Mpox is transmitted from animal to animal, animal to human and human to human. MPXV enters the body through mucous membrane and broken skin. It is diagnosed based on clinical symptoms, patient history, epidemiological information and different diagnostic tests. Pre and post prophylaxis vaccination, supportive therapy, antiviral treatments, taking preventive measures at different stages of virus transmission can reduce the disease burden.
Virus
Monkeypox/ mpox is a viral zoonotic disease. It is caused by monkeypox virus belongs to genus Orthopoxvirus under subfamily Chordopoxvirinae and family Poxviridae. It is 200-250 nm in diameter and the genetic material looks like brick shape enclosed within a lipo-proteinaceous sheath. The virion has five distinct structures like nucleocapsid, biconcave dumbbell shaped core, lateral body, membrane and surface tubules. MPXV genome is linear double-stranded DNA of about 190 kb consisting of about 190 ORFs. There are two genetic clades i.e. Central African clade (Clade I) and West African clade (IIa & IIb) (Sajio et al., 2009). The West African clades are less lethal than central African clades. The enhanced virulence of Central African clade is due to its complement enzyme inhibitors (Sapkal and Agarwal, 2022) which blocks host complement initiated virus neutralization. A novel emerging Clade-Ib has been reported with deletion in C3L gene from mpox outbreak cases in South Kivu province, September, 2023 to May, 2024 (Masirika et al., 2024).
History
The virus was first identified in a laboratory monkey (Cynomolgus) in Denmark in 1958 (Von Magnus et al., 1959). As it was initially isolated from a monkey, it was called as monkeypox virus. The first case of human infection was reported in 9 months old boy in Democratic Republic of the Congo in 1970 (Marennikova et al., 1972). Due to termination of small pox vaccination after its eradication in 1970s, the MPXV incidences increased. Growing contact between humans and small mammals due to deforestation, climate change, civil war, demographic changes, migration etc. has amplified mpox incidences. Following outbreak of mpox in USA in 2003-2004, it was given considerably attention. Before 2022 outbreaks, mpox was considered as endemic in West and Central Africa. However, as of 12th September, 2022, the US Centers for disease control and prevention (CDC) documented 57,995 confirmed cases of mpox (Huang et al., 2022) in 100 countries. As of 16th January 2023, 84716 confirmed cases of mpox in 110 countries and 80 deaths were reported according to WHO. It was declared as public health emergency of international concern (PHEIC) in July 2022. However, in May 2023, it is no longer considered as public health emergency of international concern as the number of confirmed cases declined (Lu et al., 2023). Between January, 2022 to 31st July, 2024, 121 countries reported 1,03,048 mpox cases and 229 deaths as per WHO (https://pib.gov.in/PressReleasePage.aspx?PRID=2049201). The fatality rate varies from 1-10%.Mpox cases were not detected in India until 31st May, 2022 (William and Madan et al., 2023). After that as of 17th November 2022, 17 cases of mpox have been documented (Krishnan et al., 2024). The suspected and confirmed cases of mpox were detected in different states and UT of India like Kerala, Delhi, Uttar Pradesh, Bihar and Telangana. First confirmed case of mpox was detected in 35 years old male in Kollam, Kerala on 14th July, 2022 with travel history to UAE (William and Madan et al., 2023). The first death due to mpox was recorded in 22 years old male from Kerala in 30th July, 2024 (Krishnan et al., 2024). In India 30 cases of mpox have been reported since July 2022 (https://pib.gov.in/PressReleasePage.aspx?PRID=2049201). Recently in September 2024, a new mpox case (Clade-II) was detected in a 26 years old traveler from Haryana and a highly transmissible clade-1b was identified in 38 tears old person from Kerala with travel history to UAE (https://www.weforum.org/agenda/2024/09/mpox-in-india-and-other-top-health-stories/).
Transmission
Rodents from Africa like rope and tree squirrels and giant pouched rats are considered as largest reservoir of MPXV. It has been detected in many other species like striped mice, dormice, rabbit and monkeys (Petersen et al., 2o19). The virus can be transmitted from rodents to monkeys and apes. Animal to animal transmission occurs through contact with respiratory droplets, skin sores and body fluids of infected animal. The virus is transmitted from infected animal to human through direct or indirect contact with infected tissues or body fluids of animals, scratch, bite, bushmeat etc. The virus enters into human body through respiratory tract or mucous membrane or through injured skin. The human-to-human transmission occurs mostly through respiratory route via coughing, sneezing etc. vial large respiratory droplets, sexual contact and direct or indirect contact with infected lesions, body fluids, contaminated objects etc. Vertical transmission of MPXV can occur from infected mother to the newborn.
Pathology
The virus has four stages of infection like fusion, entry, replication and release. The virus enters the host cells via endocytosis and fusion. It’s life cycle occurs in the cytoplasm. There are two different types of virions are formed labeled as intracellular mature virion with single membrane accountable for transmission between hosts and extracellular enveloped virion with triple membrane responsible for detachment and diffusion within the host (Li et al., 2023). The MPXV has several viral proteins which enhances its virulence. The virotransducer protein interacts with apoptotic pathways, virostealth inhibits MHC-1 and CD4, viromimic diminishes host cytokine impact and virokines which emulates host cytokine and chemokine impact (Stilpeanu et al., 2023). MPXV impairs NK cell function, decreases IFN-γ and TNF-α secretion, produces lymphopenia by damaging lymphoid organs like thymus, tonsil, spleen and lymphoid organs, produces cytokine storm associated with Th2 helper cells, inhibit type-I interferon secretion and evades antiviral innate immunity, increases granulocyte and monocyte population, inhibits complement system etc. which led to more serious clinical disease. (Li et al., 2023). The antibodies induced by mpox infection also enhances virus entry and replication (Li et al., 2023).
MPXV enters the body through mucous membrane and through broken skins. After entering into the body, it spreads throughout the body via immune cells and direct virus access to lymphatic vessels and localize in the regional lymph nodes during latent period up to two weeks. After this period, the infected persons exhibit fever, chills, headache, muscle pain, backache, lymphadenectasis, lymphadenopathy, fatigue and exhaustion which lasts for 3 days. Later, rashes develop in different body parts starting from head and face. In non-endemic area, genital rash is commonly observed. The flat rashes (macules) then transform gradually into papule (raised from skin), vesicles (filled with clear fluid), pustules (filled with yellowish liquid), crusts and then scars (Lu et al., 2023). In immunocompromised persons, severe lesions like sepsis, inflammation of multiple organs like heart, brain, gastrointestinal tract, respiratory tract etc., hemorrhages, necrosis, ocular infection subsequent corneal ulcer etc. were noticed. Virus evolution is favored in immunocompromised persons. The central African strains/ Congo Basin strains affect skin, respiratory, urogenital, lymphoid, reticuloendothelial system and gastrointestinal tract more severely. The West African mpox strains affect only skin, lymphoid and reticuloendothelial system.
Histopathologically, ballooning degeneration of keratinocytes, dermal oedema and acute inflammation were observed in the vesicular stage. In the pustular stage, dermal necrosis with dead keratinocytes, shadow cells, dermal neutrophil infiltration with neutrophilic exocytosis, cytoplasmic eosinophilic inclusions (Guarnieri bodies), multinucleated keratinocytes, ground glass appearance of keratinocytes with basophilic halo etc. were observed (Moltrasio et al., 2023).
Diagnosis
Monkeypox can be diagnosed based on clinical symptom, patient history, epidemiological information and diagnostic tests like conventional and real time PCR, sequencing, recombinase polymerase amplification, loop mediated isothermal amplification, restriction length fragment polymorphism, virus culture, electron microscopy, serology for detection of IgM and IgG antibody like ELISA, Western blot, immunohistochemistry, histopathology etc. (Huang et al., 2023; Karagoz et al., 2023). A novel multiplex microsphere serological immunoassay was developed using mpox specific peptide and cross-reactive Ortho- poxvirus peptide to detect infected persons within vaccinated population (Yates et al., 2023). A point of care testing method i.e. nanoparticle based lateral flow assay targeting complement genes was developed to distinguish between two clades of mpox virus (Jin et al., 2024). The samples from skin lesion like swab, exudate, tissues from vesicles, crusts, nasopharyngeal swab, oropharyngeal swab, saliva, blood sample, serum sample etc. are suitable for monkey pox confirmation. The monkeypox should be differentiated from herpes simplex, varicella zoster, molluscum contagiosum, para poxvirus infection, scabies, measles, bacterial infections etc.
Management, control and prevention
Small pox vaccine can provide protection against monkey pox, reduce its prevalence and ameliorate clinical disease. JYNNEOS (replication deficient and attenuated vaccinia virus MVA-BN strain) and ACAM2000 (replication competent live vaccinia virus) vaccines are currently available for pre-exposure prophylaxis and post exposure prophylaxis within 4 days or maximum within 14 days of infection. JYNNEOS which is a third-generation vaccine is considered safer than ACAM2000, a second-generation vaccine because of lesser chances of occurrence of myopericarditis and encephalitis. Ring vaccination can be carried out to break the mpox transmission cycle. Mass vaccination is not preferred in mpox cases as all the people are not under high risk (Chakraborty et al., 2022). LC16m8 is another third-generation vaccine which provides protection to non-human primates. Recently, m-RNA-lipid nanoparticle vaccine encoding four important mpox surface antigens and quadrivalent m RNA vaccine (m RNA-A-LNP and m RNA-B-LNP) were reported to provide robust immunity against lethal Ortho poxvirus (Freyn et al., 2023; Sang et al., 2023). The following preventive measures like public awareness, isolation of the infected persons or animals, avoiding contact with sick persons, infected animals, animals carrying mpox and contaminated objects like clothing, fomites, bodily secretions and excretions, proper cooking of animal meat, proper washing and sanitation of hands, using personal protective equipment’s when required, proper cleaning and disinfection of contaminated places, pre and post exposure vaccination for health care workers etc. can reduce the disease burden. Proper supportive therapy and treatment with antiviral drugs like Cidofovir, Brin cidofovir, Tecovirimat should be provided to mpox infected persons. Vaccinia virus immunoglobulins, a hyperimmunoglobulin can reduce viraemia and mortality (Malik et al., 2023). Novel synthetic anti monkey pox antibody is under development. For inactivation of mpox virus, physical treatment like heat (56ºC for 40 min, 70ºC for 10 min and 95º C for 5 min) and chemical treatment like β-propiolactone (1:1000 volume ratio with virus) are found effective and for disinfection, ethanol (75%) and micro chem plus (2% or 5%) are effective (Li et al., 2024). All the above measures are important keys for effective reduction of mpox burden.
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