Pharma Focus America

Monkey Pox: A viral disease creating trepidation but not pandemic

Parag Tarapada, B. Pharm Student, Pharmacy Section, L. M. College of Pharmacy

Nija Patel, B. Pharm Student, Pharmacy Section, L. M. College of Pharmacy

Mansi Athalye, Assistant Professor, Department of Pharmaceutics at L. M. College of Pharmacy

After experiencing the pandemic of COVID-19, the advent of Monkeypox- A viral disease in 2022 has fetched the attention of researchers. It is a zoonotic viral disease occurred in various countries called non-endemic. Though not pandemic, the research is proceeding toward the knowledge of disease transmission, treatment strategies including vaccines, and the policymaking to prevent the spread of the disease.

Monkeypox is a viral disease that can be infected in humans and other animals by monkey pox virus. It is the zoonotic virus that belongs to the genus Orthopoxvirus (1, 2) . The variola virus which causes smallpox belongs to the same genus (1) . Monkey pox is infected in humans as two types, first is the West African type and the second is the central African (Congo Basin) type (3) . West African type is a less severe disease as compared to the Central African (Congo Basin) type (3) . Monkeypox virus has double stranded DNA present in the nucleus (4) and the virus is also found in Gambian pouched rats (Cricetomys gambianus), dormice (Graphiurus spp.) and African squirrels (Heliosciurus, and Funisciurus). The transmission of Monkeypox may occur through animal to humans specifically who use animal as their prime source of food (5, 6) .

Though, the prevalence of the disease is high in the African region, the first detection of the disease occurred in laboratory monkeys at Copenhagen, Denmark in the year 1958 after then many species of animals are thought to be the reservoir of the monkeypox virus. In 1970, the first incidence of the disease was reported in a 9-month-old baby at Democratic republic of Congo, previously known as Zaire (7-9) . Then after, sporadic cases had been reported from west and Central Africa was endemic at the Democratic Republic of Congo. During 1981-1986 (10) , the cases of Monkeypox increased to greater than 300 in DRC which was thought to spread by direct contact of animals and in 1996, the spread of disease was detected by human transmission (1) . Till 2003 Monkeypox was thought to be confined to the rain forests of central and western African regions until the first Monkeypox case was reported in 2018 in the UK (6) . The disease then appeared widespread in 2022 in countries of other than Africa such as America, Australia, Asia and Europe (8, 11, 12) .

The MPVX F3 protein of Monkeypox is homologous to the VACV E3 protein of the vaccinia virus. The F3 protein in the genomic sequence of this virus has a full functional and complete C-terminal dsRNA binding domain. In the N-terminal of Z-NA binding domain, the first thirty- seven amino acids are deleted. It also possesses host range phenotype and Interferons similar to the wt VACV (wild type VACV) and thus it has a greater capacity to inhibit antiviral cellular immune response than vaccinia virus (13) .

The disease transmission occurs from animal to humans by various means such as spreading by animal bites, scratching, handling of infected meat, bush meat preparation and via direct contact of fluid or lesion (14) . The infection gets spread through contaminated objects (through airborne route), contact with infectious body fluids, sharing of common facilities and   during intercourse (14, 15) . This infectious virus enters the human body through nose, mouth, eye’s mucus membrane, respiratory tract and through broken skin (16) . There is an increased risk of transmission from an infected pregnant woman to the placenta and from breast-fed mother to child (17) . The typical signs and symptoms of Monkeypox includes fever, headache, fatigue, chills, exhaustion, cough, sore throat etc. (6,15, 17,18) . It also exhibits a few severe signs such as swollen glands and lymph nodes, pimple like rashes, glisters, blisters etc. (15, 17) . Many people experience flu-like signs followed by rash after 1 to 4 days which lasts for about 2 to 4 weeks (19) . These lesions appear on different body parts such as the neck, chest, and mouth, below the jaw, anus and feet. The infection can spread at any time of persistence of symptoms till it gets healed and fresh skin appears (17) . The condition aggravates if not treated on time and it results in various signs such as sepsis, encephalitis, pneumonia and even vision loss in case of severe infection of the eye (6) . In the adverse situation of infection during pregnancy, the chances of birth defects persist (20, 21) .
 
The diagnosis of Monkey pox infection is very crucial to prevent the transmission of the disease. The clinical signs and symptoms of monkey pox and smallpox resembles each other and hence advanced methods are necessitated to distinguish the causative factor (22) . The researchers are working on the diagnostic method to identify specifically the infection caused by Orthopoxvirus. Though, the similarity is possessed by the similar genomic structures in monkeypox virus and variola strain, the molecular techniques are there which can distinguish it such as polymerase chain reaction (PCR) technique (6) . The PCR technique can be used for detection of two genes wherein the one assay, thirteen types of various Eurasian orthopoxviruses can be identified which specifically targets the DNA gene similar to that of the COP E9L gene of vaccinia strain of the virus. The other assay technique specifically targets the ortholog protein COP B5R gene and thus becomes specific to only Monkeypox virus (22) . This sensitive method utilize the fact of single nucleotide polymorphism present in the small sequence of virus ortholog gene to Copenhagen B5R gene (22) .

These methods are advantageous though it diagnoses the virus as long as the infection persists in the specimen. Once it is cleared, it is not able to detect the monkeypox virus. Therefore, the  newer techniques are being developed to detect the infection based on the host immune response. Another method is through observation of cross-reactive immune response which involves the prior vaccination of smallpox and then the determination through standard antibody test. Though this method is complicated and does not accurately diagnose the disease (23) . Further, IgM (immunoglobulin M) assay technique is also used utilizing the fact that anti-vaccinia IgM antibodies post smallpox vaccination should be absent. Another method for the effective diagnosis of monkeypox is Enzyme-linked immunosorbent assay (ELISA) technique wherein the ratio of antibody titres of vaccinia virus and monkeypox virus is determined (24, 25) .

Moreover, the BR 219 (Brighton red 219) gene from the monkeypox ortholog of cowpox virus can also be utilized for the diagnosis of the disease which is protein encoded. This gene is encoded for the membrane associated glycoprotein which is not available in the vaccinia virus. To discriminate the recently occurred monkeypox infection and the prior small pox vaccine, the peptide from this protein can be utilized for ELISA testing. Besides, another technique is based upon the cellular immune response against the specific pathogens wherein the measurement of orthopox virus specific number of T-cells is carried out which is still under research (24) .
 
Currently, for the treatment of Monkeypox virus, no any specific drug or vaccine is available (26) Instead the small pox vaccine is used. The study carried out in 1988 suggested that this vaccine is 85% effective against the monkeypox in terms of preventing the infection (27) . Though, the vaccine based on the modified vaccinia Ankara is approved for monkeypox and smallpox infection. The anti-viral drugs such as tecovirimat and Cidofovir are used as a treatment option of the Monkeypox (28, 29) . The CDC (Centers for Disease Control and Prevention) recommends the smallpox vaccine to the individuals who are involved in the research or are taking care of the infected animal or the human to prevent any kind of pox virus (30) . In the European Union and the United states, Tecovirimat is approved for the various poxvirus and so for Monkeypox infection also (31) . Along with anti-viral agents, two vaccines named as ACAM2000 and JYNNEOS (also called as imvanex or imvamune) are given to treat Monkeypox in USA licensed by USFDA (6) . The ACAM2000 is administered by single dose Percutaneous route wherein within 4 weeks of administration, immunological reactions occur and it heals within 6 weeks. The study is also supported by human clinical trials and animal studies. Though, in current outbreak situation, no information or data is available for pre- and post-exposure prophylaxis against infection so individuals with weak immune systems are advised to get refrained from the vaccine (17) . It is also not advisable in case of immune deficiency disorders, atopic dermatitis, cardiac disease, and any exfoliated skin disorder and in pregnancy. Another vaccine named JYNNEOS is live virus vaccine of which two injections are given by subcutaneous route with a gap of four weeks, the effect of which develops after many weeks. Though studied in animals, it also lacks the data for its effectiveness for pre and post prophylaxis. It is contraindicated in the persons having allergy of ciprofloxacin, gentamicin and egg protein. It is proven safe in pregnant and breastfeeding mothers as well as in persons infected with HIV (17) . Thus, to prevent the spread of the disease, the person should avoid the direct contact with the infected person and the patient should be isolated till the symptoms alleviate (6, 17) .
 
Therefore, the Monkey pox virus is similar to smallpox in terms of signs and symptoms but indicates less severe symptoms. It also shows similarity with chickenpox in symptoms but both are caused by different virus and monkeypox takes a longer time to get healed. The Monkeypox though a viral disease, but in comparison to SARS-CoV-2, it is less severe and till July 2022, no significant deaths are reported. The cases of Monkeypox infection are approx. 3261 in Europe with 793, 142, 210, 73 and 5 cases in UK, USA, Canada, Africa and India respectively with only one death reported in Africa (32) . The infection is treated by smallpox vaccine as no any specific monkeypox vaccine is available. Moreover, the Monkeypox virus mutates very slowly as compared to SARS-CoV-2 so pose less threat as compared to COVID-19 (6,17) .

Thus, though Monkeypox viral infection is spreading to human and there is outbreak of the disease, it is not as lethal as the world has experienced in case of COVID-19.

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Parag Tarapada

Parag Tarapada is a student of B. Pharmacy at L. M. College of Pharmacy, Ahmedabad, Gujarat, India. He is working on the project of a Nano vesicular system for the treatment of infectious diseases.

Nija Patel

Nija Patel is a student of B. Pharmacy at L. M. College of Pharmacy, Ahmedabad, Gujarat, India. She is working on the project of a Nanoparticulate system for the treatment of CNS disorder.

Mansi Athalye

Mansi Athalye is an Assistant Professor in the Department of Pharmaceutics at L. M. College of Pharmacy, India with approx. 12 years of teaching and research experience. She has published 17 papers in international and national journals and has presented 25 papers in various conferences as author and co-author with 1 Indian Patent granted in 2018.

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