Topic: Multi-country monkeypox outbreak, transmission, vaccine and treatment: Situation Update

Speaker: Prof Mulazim Hussain Bukhari, Pakistan

25^th June, 2022, Saturday, 9.30-10.30am

• The World Health Network has declared monkeypox a pandemic as per a press release dated June 22,2022. It stated “By taking immediate action, we can control the outbreak with the least effort and prevent consequences from becoming worse… The actions needed now only require clear public communication about symptoms, widely available testing, and contact tracing with very few quarantines. Any delay only makes the effort harder and the consequences more severe”. However, as cases surge in Europe, the WHO is considering declaring monkeypox a global emergency
• As of June 2022, there were 3308 confirmed cases of monkeypox in 42 countries.
• The first case of monkeypox was reported in 1958 in animals (monkey; hence the name). The first human case was reported in 1970 in 11 African countries due to travel and animal import.
• The first case of monkeypox in the current outbreak was reported on 4^th May with history of travel to Nigeria. A week from this, cases started increasing. After nearly a month, the monkeypox virus had spread to more than 21 countries with around 200 confirmed cases and more than 100 suspected cases in non-endemic countries. But now cases are showing a decline.
• As of 22^nd June, UK had 793 cases, Germany 521, Spain 520, France 277, Canada 210 and the US had 155 cases.
• Monkeypox is a rare disease caused by the enveloped double-stranded monkeypox virus, which belongs to the Orthopoxvirus genus, the same genus as the smallpox virus. There are two distinct clades of the monkeypox virus: the central African (Congo Basin) clade and the west African clade. The west African Congo Basin clade has caused more severe disease and was thought to be more transmissible.
• It is a DNA virus with low mutation rate @1-2 base pairs per year. In contrast, the coronavirus undergoes rapid mutations as it is an RNA virus.
• There were no cases in Nigeria till 1978. The first case was recorded in 2017 in a 11-year-old male and now there are more than 500 cases. From 1978-2022, 47 base pair mutations have been recorded in Nigeria. 
• Cameroon is the only country where both clades of the monkeyvirus have been found.
• The natural hosts of the monkeypox virus are Rope squirrels, tree squirrels, Gambian poached rats, dormice and different species of monkeys.
• The R0 ranges between 0 to 1, which means that the infection is very slow. A person within close vicinity (less than 6 feet) can get droplet infection and the virus remains viable for 3+ hours.
• Zoonotic transmission can occur from direct contact with blood, bodily fluids, skin/fur or mucosal lesions of the infected animals.
• Eating inadequately cooked meat and other animal products of the infected animals is a possible risk factor. People living in or near forested areas may have indirect or low-level exposure to infected animals.
• Close physical contact is a risk factor for human to human transmission; infection spread is also possible through close contact with infected respiratory tract secretions or skin lesions.
• The longest documented chain of transmission in a community has risen in recent years from 6 to 9 successive person-to-person infections. This probably reflects the declining immunity due to cessation of smallpox vaccination. 
• Its not clear yet if there is any association with long Covid-19.
• Mother to fetus transmission of the virus can also occur through the placenta or during close contact during and after birth. Transmission via milk has not been reported.
• The incubation period of monkeypox is usually 6-14 days, but can vary from 5 to 21 days. The infection can be divided into two phases.
• The first three days of the infection, the invasion period, is characterized by fever, intense headache, back pain, myalgia, intense asthenia and tiredness.
• After three days, the infection is characterized by lymphadenopathy and skin rash within 1-3 days of fever. The rash tends to be more concentrated on the face and extremities rather than on the trunk. The illness lasts for 2-3 weeks. Lymphadenopathy is the only feature to differentiate it from smallpox and chickenpox.
• In majority of cases (95%), rash affects the face; it is also seen on the palms and soles (75% cases), oral mucous membranes (70%), genitalia (30%), conjunctivae (20%) and cornea.
• The rash progresses in a sequential manner from macules to papules, vesicles, pustules and crusts which fall off after drying.
• The number of lesions varies from a few to several thousand. In severe cases, these lesions can coalesce to form a large lesion and large sections of skin slough off.
• Following the eradication of smallpox, vaccination against smallpox was stopped globally. Persons younger than 40-50 years of age, who are not vaccinated may be more susceptible to monkeypox.
• Monkeypox is usually a self-limited disease with symptoms lasting from 2-4 weeks. Severe cases occur more commonly among children.
• Complications of monkeypox include secondary infections, pneumonia, sepsis, encephalitis and infection of cornea leading to loss of vision. 
• Mortality is up to 11%; underlying immune deficiencies may lead to worse outcomes.
• Differential diagnosis clinically includes other rash illnesses such as chickenpox, measles, scabies, syphilis, bacterial skin infections and medication-associated allergies.
• Confirmation of monkeypox depends on the type of specimen, quality of specimen and laboratory test performed. Specimens should be packaged and shipped in accordance with national and international requirements.
• The optimal diagnostic samples are from skin lesions: roof, fluid from vesicles, pustules and dry crusts.
• PCR is the preferred lab test due to its accuracy and sensitivity.
• Biopsy is an option where feasible. Lesion samples must be stored in a dry, sterile tube (no viral transport media) and kept cold.
• PCR on blood, semen and saliva are inconclusive. Serology and antigen detection methods are not recommended for diagnosis or case investigation as orthopoxviruses are serologically cross-reactive and do not provide monkeypox-specific confirmation.
• Recent or remote vaccination with a vaccinia-based vaccine i.e., anyone vaccinated before the eradication of smallpox or more recently vaccinated due to higher risk e.g., lab personnel can lead to false positive test.
• Along with the specimens, it is important to provide patient information such as date of onset of fever/rash, date of specimen collection, age, stage of rash.
• Vaccination against smallpox is about 85% effective in preventing monkeypox.
• There are two types of vaccines: ACAM2000 and Jynneos.
• Jynneos is replication-deficient modified vaccine Ankara with fewer serious adverse events including cardiac adverse events. It is administered subcutaneously in two doses in a gap of 28 days. The ACAM2000 is a replication-competent vaccinia virus vaccine. There is a risk of inadvertent inoculation and autoinoculation and adverse events. It is given percutaneously by multiple puncture technique in single dose.
• It is important to raise public awareness about risk factors and the measures they can take to reduce exposure to the virus. Educate the public, do not panic.
• At-risk persons such as laboratory personnel, rapid response teams and health workers should be offered the vaccine. There should be a policy regarding this.
• Surveillance and rapid identification of new cases is critical to contain the outbreak.
• The most important risk factor for infection is close contact with infected persons. Healthcare workers and household members are at a greater risk of infection.
• Healthcare workers caring for suspect or confirmed cases should strictly implement standard infection control precautions. If possible, persons who have taken the smallpox vaccine should be selected for patient care. But cases have been reported in previously infected cases as IgG declines after 3 years.
• Unprotected contact with wild animals, especially those that are sick or dead must be avoided.
• All foods containing animal meat should be thoroughly cooked prior to eating.
• Potentially infected captive animals should be isolated from other animals and placed into immediate quarantine for a month. Regulations are in place in some countries restricting the import of rodents and non-human primates.
• There is no specific treatment for monkeypox. Treatment is symptomatic with plenty of fluids and nutritious diet; complications should be managed to prevent long-term sequelae. Treat secondary bacterial infections as indicated.
• If required, tecovirimat, an antiviral drug can be given in doses of 600 mg twice daily for 14 days. It was FDA approved in 2018. If used for patient care, it should ideally be monitored in a clinical research context with prospective data collection.
• Cidofovir and brincidofovir have shown in vitro activity against pox viruses and human studies are lacking. Brincidofovir was FDA approved last year, while cidofovir is not FDA approved.
• Vaccinia immune globulin (VIG) is another option but data about its effectiveness is insufficient. It can be considered for prophylaxis in an exposed person with severe T cell immunodeficiency, in whom smallpox vaccine after exposure to monkeypox is contraindicated.

Participants

Member National Medical Associations

Dr Yeh Woei Chong, Singapore, Chair of Council CMAAO

Dr Wasiq Qazi, Pakistan, President-elect CMAAO

Dr Ravi Naidu, Malaysia

Dr Angelique Coetzee, South Africa

Dr Akhtar Hussain, South Africa

Dr Salma Kundi, Pakistan

Dr Tashi Tenzin, Bhutan 

Invitees

Prof Mulazim Hussain Bukhari, Pakistan 

Dr Mohammed Munir, Pakistan

Dr Monica Vasudev, USA

Dr Patricia La’Brooy

Dr EC Ng

Dr Soo Hong Chong

Dr Carol Lim

Dr Soh Hsien Wern Gavin

Dr Tan Chin Lock

Dr Wong Ted Min

Dr S Sharma, Editor IJCP Group

Moderator

Mr Saurabh Aggarwal