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Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 4  |  Page : 221-226

Monkeypox: An alarming global health emergency


Department of Medicine, MVJMC and RH, Bengaluru, Karnataka, India

Date of Submission01-Aug-2022
Date of Decision05-Sep-2022
Date of Acceptance06-Sep-2022
Date of Web Publication25-Oct-2022

Correspondence Address:
Dr. Vasantha Kamath
Department of Medicine, MVJMC and RH, Hoskote, Bengaluru - 562 114, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_108_22

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  Abstract 


Monkeypox (MPX) virus is an orthopoxvirus that causes human MPX, a viral disease with symptoms indistinguishable to smallpox, which includes fever and rash. Following the worldwide eradication of smallpox in 1980, MPX emerged as the most significant orthopoxvirus infection in humans. Cases are most often reported from rural areas of Central and West African countries, particularly in regions close to tropical rainforest where people may have contact with infected animals. MPX is transmitted through direct contact with respiratory droplets of another person who has MPX in the home or in a health facility, or with contaminated materials such as bedding. Laboratory diagnostics are the principal components for the identification and surveillance of the disease, and new tests are needed for a more precise and rapid diagnosis. New therapeutics and vaccines offer hope for the treatment and prevention of MPX; however, more research must be done before they are ready to be deployed in an epidemic setting.

Keywords: Monkeypox, orthopoxvirus, smallpox, vaccine


How to cite this article:
Kamath V, Sridhar S, Reddy K D. Monkeypox: An alarming global health emergency. APIK J Int Med 2022;10:221-6

How to cite this URL:
Kamath V, Sridhar S, Reddy K D. Monkeypox: An alarming global health emergency. APIK J Int Med [serial online] 2022 [cited 2022 Dec 3];10:221-6. Available from: https://www.ajim.in/text.asp?2022/10/4/221/359442




  Introduction Top


Monkeypox (MPX) is a viral zoonosis presenting symptoms similar to smallpox, although it is less severe clinically. Smallpox was eradicated in 1980 and smallpox vaccination was subsequently stopped, since then MPX has become the most important orthopoxviral disease of public health importance. Primarily, it is found in African continent, especially Central and West Africa, occurring in areas with proximity to tropical rainforests, with a range of rodents and nonhuman primates serving as animal hosts.[1]


  History Top


Preben von Magnus first identified MPX in two nonfatal outbreaks in laboratory crab-eating macaque (cynomolgus monkey) at the State Serum Institute, Copenhagen, Denmark, in 1958.[2]

The virus was never found in Asia, and the incidence in Asian monkeys was likely due to catching the disease in confinement and transit, or contamination. In 1962 at the Walter Reed Army Institute of Research, Maryland, several monkeys had antibodies but no symptoms. In 1964 at Rotterdam Zoo, Central/South American giant anteaters first developed the disease followed by orangutans, chimpanzee, gorillas, guenons, squirrel monkey, macaques, marmosets, and gibbons. Eleven animals died of the 23 animals infected. The disease was more severe in orangutans.[3]


  Outbreaks (in Humans) Top


The first documented cases in humans were found in 6 unvaccinated children in 1970 during the smallpox eradication efforts, the first being a 9 month old boy in the Democratic Republic of the Congo (formerly Zaire).[1] Ever since 1970, human cases of MPX have been reported in 11 African countries: Benin, Cameroon, Central African Republic, the Democratic Republic of the Congo, Gabon, Cote d'Ivoire, Liberia, Nigeria, the Republic of the Congo, Sierra Leone, and South Sudan. The true burden of MPX is not known. For example, in 1996–1997, an outbreak was reported in the Democratic Republic of the Congo with a lower case fatality ratio and a higher attack rate than usual. Ever since 2017, Nigeria has experienced a large outbreak, with over 500 suspected cases and over 200 confirmed cases and a case fatality ratio of approximately 3%. Cases continue to be reported until today. Monkeypox not only occurs in countries of West and Central Africa, it is a disease of global public health importance and occurs in other parts of the world also.[1]

The first MPX outbreak outside Africa was in the USA in 2003, and it was linked to contact with infected pet prairie dogs. These pets had been housed with Gambian pouched rats and dormice that had been imported into the country from Ghana. This outbreak led to the emergence of over 70 cases of MPX in the U. S. MPX has also been reported in travelers from Nigeria to Israel in September 2018, to the United Kingdom in September 2018, December 2019, May 2021, and May 2022, to Singapore in May 2019, and to the United States of America in July and November 2021.[1]


  Agent Factor Top


MPX virus is an enveloped double-stranded DNA virus that belongs to Orthopoxvirus genus and Poxviridae family. It has two distinct genetic clades: Central African (Congo Basin) clade and West African clade. The Congo Basin clade has historically caused more severe disease and was thought to be more transmissible. Cameroon is the only country where both virus clades have been found.[1]


  Structure of Monkeypox Virus Top


MPX virus is a brick-shaped virus measuring 200–250 nm in size. It has a dumbbell-shaped core component with a linear double-stranded DNA [Figure 1].
Figure 1: Structure of monkeypox

Click here to view



  Host Factors Top


Rope squirrels, tree squirrels, Gambian pouched rats, dormice, nonhuman primates like orangutans, chimpanzees, gorillas, guenons, squirrel monkeys, macaques, marmosets, and gibbons are a set of animals susceptible to monkeypox. The natural history of MPX virus still remains uncertain.[3],[4]


  Transmission Top


  • Animal-to-human (zoonotic) transmission: It is through direct contact with the blood, body fluids, or cutaneous or mucosal lesions of infected animals, consumption of inadequately cooked meat, and other products of infected animals[1]
  • Human-to-human transmission: close contact with respiratory secretions, skin lesions of an infected person, or recently contaminated objects. Vertical transmission can occur via the placenta from mother to fetus or during close contact during and after birth[1]
  • Environment-to-human transmission: from contaminated clothing or linens that have infectious skin particles.[1]



  Clinical Features Top


MPX is usually a self-limited disease with symptoms lasting from 2 to 4 weeks. The incubation period of MPX usually ranges from 5 to 21 days. Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status, and nature of complications. The extent to which asymptomatic infection occurs is unknown. The case fatality ratio in recent times has been around 3%–6%.[4]

MPX can cause a range of clinical signs and symptoms. The initial phase of clinical illness typically lasts 1–5 days, during which time patients may experience fever, headache, back pain, muscle aches, lack of energy, and lymphadenopathy – which is a distinctive feature of this disease.[5] This is followed by a second phase, which typically occurs 1–3 days after fever subsides with the appearance of a rash.[6],[7],[8] The rash presents in sequential stages – macules, papules, vesicles, pustules, umbilication before crusting over, and desquamating over a period of 2–3 weeks. The eruption tends to be centrifugal, starting on the face and extending toward the palms and soles of the hands and feet, and can involve the oral mucous membranes, conjunctiva, cornea, and/or genitalia.[9],[10],[11]

The most common clinical symptoms are rash (96.8%), malaise (85.2%), and sore throat (78.2%).[5] The most common findings on physical examination were the classic MPX rash (99.5%); lymphadenopathy (98.6% – the cervical region was most frequently affected [85.6%], followed by the inguinal region [77.3%]); and mouth/throat lesions (28.7%).[5]


  Complications of Monkeypox Top


  • Secondary infections
  • Necrotizing soft tissue infection
  • Pyomyositis
  • Cervical adenopathy
  • Acute respiratory distress syndrome
  • Bronchopneumonia
  • Sepsis
  • Encephalitis
  • Infection of the cornea with ensuing loss of vision.



  Differential Diagnosis Top


Varicella (chicken pox)

It can be differentiated from MPX by the absence of rashes in soles and palms. Polymorphic rashes are present in different stages of development in chicken pox; however, in MPX, the rashes are sequential in nature.[12]

Disseminated herpes zoster

It is tough to distinguish between shingles and MPX since both can cause flu-like symptoms and a cluster of painful bumps. However, MPX patients get characteristic indented lesions, while shingles patients do not.[12]

Smallpox

It can be differentiated from MPX by the presence of deep rashes and also by the absence of lymphadenopathy and also fever tends to be high grade in smallpox.[7]

Measles

Measles is characterized by a fever 4–5 days before the appearance of rashes, the development of rash is rapid and present in multiple stages of development, whereas in MPX, fever is seen 2–3 days before the appearance of rashes and the development of rash is slow and rashes are present in the same stage of development.[13]

Hand foot mouth disease

It is more common in young children and characterized by sores in the mouth and a rash on the hands and feet, lymphadenopathy is usually absent, whereas MPX is seen in both adults and children and lymphadenopathy is characteristically seen.[12]

Molluscum contagiosum

Lesions are rarely found on the palms or the soles. Both MPX and molluscum contagiosum cause indented lesions. Molluscum contagiosum generally causes “hard bumps,” whereas MPX lesions are pus filled.[12]


  Recent Outbreak Top


Since January 1 and as of June 22, 2022, 3413 laboratory-confirmed cases and one death have been reported to the WHO from 50 countries/territories in five WHO regions.

The majority of laboratory-confirmed cases (2933/3413, 86%) were reported from the WHO European Region. Other regions reporting cases include the African Region (73/3413, 2%), Region of the Americas (381/3413, 11%), Eastern Mediterranean Region (15/3413, <1%), and Western Pacific Region (11/3413, <1%). One death was reported in Nigeria in the second quarter of 2022.

Polymerase chain reaction (PCR) assay data indicate that the MPX virus genes detected belong to the West African clade.

The overall risk at a global level is considered moderate since this is the first time that cases and clusters are reported concurrently in five WHO regions. The risk is considered to be high only in the European Region due to reports suggesting geographically widespread outbreak involving several newly affected countries, as well as a somewhat atypical clinical presentation of cases.

The unexpected appearance of MPX and the wide geographic spread of cases indicate that the MPX virus might have been circulating below levels detectable by the surveillance systems and sustained human-to-human transmission might have been undetected for a period of time.

The clinical presentation of MPX cases associated with this outbreak has been atypical as compared to previously documented reports.

Atypical features described include: presentation of only a few or even just a single lesion, absence of skin lesions in some cases, anal pain and bleeding, lesions in the genital or perineal/perianal area which do not spread further, lesions appearing at different (asynchronous) stages of development, the appearance of lesions before the onset of fever, malaise and other constitutional symptoms (absence of prodromal period).[14]


  Indian Picture Top


India's first MPX case was reported on July 14, 2022, from Kerala. The patient is a 35-year-old male who traveled from UAE and reached the state on July 12. India's second MPX case was reported in Kerala's Kannur district on July 18. India reported its third MPX case in Kerala on July 22. The fourth confirmed MPX case is a 34-year-old man from Delhi, with no history of foreign travel.


  Diagnosis Top


Collection of clinical samples

In case of asymptomatic patients, one should look for the development of any signs and symptoms for 21 days postexposure. If signs and symptoms develop, the specimen has to be collected as per the duration of illness.

In case of symptomatic patients, the sample has to be collected which varies based on the phase of infection. When the patient is in rash phase, the sample can be collected from lesion roof, lesion fluid, lesion base scrapping, lesion crust, nasopharyngeal swab/oropharyngeal swab, blood, and urine. During recovery phase, the sample has to be collected from blood and urine.[4]

Diagnostic modalities for monkeypox[4]

For the confirmation of MPX on the suspected clinical specimens:

  1. PCR for Orthopoxvirus genus (cowpox, buffalopox, camelpox, and MPX) will be done
  2. If the specimen shows positivity for the Orthopoxvirus, it would be further confirmed by MPX-specific conventional PCR or RT-PCR for MPX DNA
  3. In addition, virus isolation and the next-generation sequencing of clinical samples (MiniSeq and NextSeq) will be used for characterization of the positive clinical specimens [Figure 2].[4]
Figure 2: Diagnostic Modalities for Monkeypox

Click here to view



  Management Top


Symptomatic treatment

  • Skin rash: It can be treated using simple antiseptic application like mupirocin acid/Fucidin application, if extensive lesions are present lesions has to be covered with light dressing, lesions should not be touched/scratched, appropriate antibiotics to be started in case of secondary infection
  • Genital ulcers: It can be treated by sitz bath
  • Oral ulcers: It can be treated by warm saline gargle/application of oral topical anti-inflammatory gel
  • Conjunctivitis: usually, self-limiting
  • Dehydration: It can be treated by encouraging Oral rehydration solution (ORS) or oral fluid consumption; intravenous fluids can be initiated if clinically indicated
  • Fever: It can be treated by using antipyretic (paracetamol) and tepid sponging
  • Itching/pruritus: It can be treated by topical calamine lotion application and antihistaminics
  • Headache/malaise: It can be treated using paracetamol and adequate hydration.



  Monitoring and Treatment of Complications Top


The patient should be closely monitored for the appearance of any of the following symptoms during the period of isolation like pain in eye or blurring of vision, shortness of breath, chest pain, difficulty in breathing, altered consciousness, seizure, decrease in urine output, poor oral intake, lethargy. In case any of the above symptoms appear, the patient should immediately contact nearby healthcare facility.[4]


  Recent Advances in Treatment Top


Tecovirimat

It is also known as TPOXX, ST-246. Tecovirimat is licensed by the European Medicines Agency (EMA) for the treatment of smallpox, MPX, cowpox, and complications from immunization with vaccinia and by the United States Food and Drug Administration (FDA) and Health Canada for smallpox.[15],[16],[17] Tecovirimat inhibits viral envelope formation of MPX virus by targeting the viral protein p37.[18] It is available as immediate-release oral capsules administered twice daily for 14 days.[15],[19]

Dosage:

Oral: 600 mg PO every 12 h.

Intravenous:

  • 3 kg to <35 kg: 6 mg/kg every 12 h
  • 35 kg to <120 kg: 200 mg every 12 h
  • More than 120 kg: 300 mg every 12 h.


Duration of treatment: 14 days.[20]


  Cidofovir Top


It is also known as Vistide. Cidofovir is approved by the FDA for the treatment of cytomegalovirus.[18] It inhibits the replication of MPX virus by inhibiting DNA polymerase and is administered intravenously. It has shown activity against poxviruses in laboratory and animal studies.[21] Cidofovir-associated renal toxicity and electrolyte abnormalities have been reported.[22]

Dosage:

Intravenous: 5 mg/kg IV once weekly (must be given with at least 1 L of 0.9% normal saline over a 1–2-h period before each infusion). It must be given with oral probenecid.

Duration of treatment: Once weekly × 2 weeks and then once every other week. [20]


  Brincidofovir Top


It is also known as CMX001 or Tembexa. Brincidofovir is approved by the EMA and FDA for the treatment of smallpox and has been shown to have antiviral activity against double-stranded DNA viruses, including poxviruses.[22] It inhibits the replication of MPX virus by inhibiting the polymerase-mediated synthesis of DNA and is available as an oral tablet or suspension administered to patients as two doses 1 week apart. Reported side effects of this medication include elevation of hepatic transaminases, diarrhea, nausea, vomiting, and abdominal pain.[23]

Dosage:

  • Oral: <10 kg: 6 mg/kg
  • 10–48 kg: 4 mg/kg
  • More than 48 kg: 200 mg.


Duration of treatment: Once weekly for 2 doses, on days 1 and 8.[20]


  Vaccinia Immune Globulin Intravenous Top


It is used for the treatment of complications due to vaccinia vaccination and aberrant infections induced by vaccinia virus. Information is not available on the efficiency of VIG in the treatment of MPX virus infection. The use of VIG has no proven benefit in the treatment of MPX. VIG can be considered for prophylactic use in an exposed person with severe immunodeficiency in T-cell function for which smallpox vaccination following exposure to MPX virus is contraindicated.[24]


  Vaccine Top


ACAM2000 and JYNNEOS (also known as Imvamune or Imvanex) are the two currently licensed vaccines in the United States to prevent smallpox. ACAM2000 is a live vaccinia virus preparation that is inoculated into the skin by pricking the skin surface. A lesion will develop at the site of the vaccination (i.e. a “take”) following a successful inoculation. Individuals who receive vaccination with ACAM2000 must take precautions to avoid the spread of the vaccine virus and are considered vaccinated within 28 days. JYNNEOS is a live virus that is nonreplicating. It is administered as two subcutaneous injections 4 weeks apart. There is no visible “take” and, as a result, no risk for spread to other parts of the body or other people. People who receive JYNNEOS™ are not considered vaccinated until 2 weeks after they receive the second dose of the vaccine.[25]

Preexposure prophylaxis

The Advisory Committee on Immunization Practices recommends that people whose jobs may expose them to orthopoxviruses, such as MPX, get vaccinated with either ACAM2000 or JYNNEOS to protect them if they are exposed to an orthopoxvirus.[25]

Postexposure prophylaxis

Vaccine can be given within 4 days from the date of exposure in order to prevent the onset of the disease. If vaccine is given between day 4 and day 14 after the date of exposure, vaccination may not be able to prevent the disease but it can reduce the symptoms of disease.[25]

Adverse events following vaccination

ACAM2000 may cause myocarditis and pericarditis. Other serious side effects include swelling of the brain or spinal cord, problems with the vaccination site becoming infected, and accidental infection of the eye with the vaccine virus.[26]

JYNNEOS can cause redness, soreness, swelling, and itching where the shot is given. Fatigue (tiredness), headache, and muscle pain can also sometimes happen after vaccination.[27]

Smallpox vaccine is at least 85% effective in preventing MPX.[25]


  Preventive Measures Top


Reducing the risk of human-to-human transmission

Rapid identification of new cases is critical for outbreak containment. Health workers and household members are at a greater risk of infection. Health workers caring for patients with suspected or confirmed MPX virus infection, or handling specimens from them, should implement standard infection control precautions like avoiding contact with any materials, such as bedding, that has been in contact with a sick person, isolating infected patients from others, practicing good hand hygiene after contact with infected animals or humans, and using appropriate personal protective equipment when caring for patients. Samples taken should be handled by trained staff working in suitably equipped laboratories.[1]

Reducing the risk of zoonotic transmission

Most of the human infections have resulted from a primary, animal-to-human transmission, hence unprotected contact with wild animals, especially those that are sick or dead, including their meat, blood, and other parts must be avoided.[1]

Preventing monkeypox through restrictions on animal trade

Captive animals that are potentially infected with MPX should be isolated from other animals and placed into immediate quarantine.[1]


  Conclusion Top


The emerging MPX outbreak in nonendemic areas has gathered international interest.

The available data in this review demonstrate how incomplete and fragmented the information about MPX epidemiology still is, which leads to a potential underestimation of the magnitude and severity of MPX outbreaks. Despite being described for the first time in a human in 1970, there are no standard guidelines for clinical management, therapeutics, or vaccines. MPX is a significant health concern for people living in endemic regions as well as in nonendemic regions. Appropriate and effective interventions and active surveillance activities are important to prevent increased transmission efficiency or virulence. MPX is the most important orthopoxvirus in humans, definitely in the endemic areas and perhaps globally, and hence needs further attention.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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  In this article
Abstract
Introduction
History
Outbreaks (in Hu...
Agent Factor
Structure of Mon...
Host Factors
Transmission
Clinical Features
Complications of...
Differential Dia...
Recent Outbreak
Indian Picture
Diagnosis
Management
Monitoring and T...
Recent Advances ...
Cidofovir
Brincidofovir
Vaccinia Immune ...
Vaccine
Preventive Measures
Conclusion
References
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