CDC experts talk about disinfection | Teach you the prevention and control of monkeypox virus

Recently, a number of countries, including the United Kingdom, Portugal, and the United States, have reported unusual cases of monkeypox. The World Health Organization also issued an outbreak alert a few days ago, saying that existing information indicates that human-to-human transmission of the monkeypox virus is occurring, and more cases may be found in countries that have reported cases and other countries in the future.

Professor Ni will introduce the etiology and epidemiology of monkeypox in detail, as well as how to prevent and control it, so that everyone can fully understand the monkeypox virus, be vigilant, and not panic when encountering "pox"!

Prevention and control of "monkeypox"

Monkeypox (Monkeypox) is an emerging viral zoonotic disease caused by monkeypox virus (MPXV) and is the most important Orthopoxvirus for human infection in the era after the eradication of smallpox.

In 1958, MPXV was first reported by the National Serum Institute in Copenhagen, Denmark. The first human cases of MPXV infection were detected in a remote village (Bokenda) in the Democratic Republic of Congo in August 1970.

1 Shashank Hudkar

Notably, in 1977, the last case of naturally acquired smallpox was reported globally. In 1978, the last case of laboratory-acquired smallpox infection was reported globally. In 1980, WHO announced the global elimination of smallpox, and subsequently stopped smallpox vaccination worldwide. With the cessation of smallpox vaccination, the level of vaccine immunity in the population has been declining year by year. In addition, the number of people born after 1980 who do not need to be vaccinated with vaccinia has increased, and the continuous accumulation of susceptible people worldwide has created conditions for MPXV to enter the population. Currently, the number of reported monkeypox cases and their geographic scope is increasing, with at least 131 confirmed or 106 suspected cases of monkeypox reported in at least 19 countries outside Africa since May 2022 alone, becoming the second most important post-COVID-19 disease in the world. Another public health issue of global concern after the epidemic.

"Etiology"

Monkeypox virus (MPXV) belongs to Poxviridae family (Poxviridae), vertebrate poxvirus subfamily (Chordopoxvirinae), orthopoxvirus (Orthopoxvirus, OPV), monkeypox virus species (Monkeypox virus); it is double-stranded DNA (double- Stranded DNA, dsDNA) virus containing envelope, is a kind of virus with complex structure and large particle size, the shape is like a brick, the length is 220~450nm, and the width is 140~260nm. Therefore, MPXV can be identified by optical microscopy, but its ultrastructure has to be resolved by electron microscopy. Viruses are composed of four main components, the Core, Lateral bodies, Outer membrane, and Outer lipoprotein envelope (see Figure 2).

Figure 2 Schematic diagram of poxvirus particles

DNA viruses are generally believed to be better at self-detecting and repairing mutations than RNA viruses, which means that MPXV is unlikely to suddenly mutate into a human-like coronavirus and spread rapidly from person to person. However, scientists' analysis of the recently isolated MPXV showed that it mutated much faster than expected and should be of great concern.

There are two distinct genetic clades of MPXV, the Central African (Congo Basin) clade and the West African clade. The Congo Basin branch has historically caused more severe disease and is more contagious. So far, the geographic dividing line between the two viral clades is in Cameroon—the only country where both clades have been found together.

"Epidemiology"

Various animal species have been identified as reservoir hosts for MPXV, including rodents, mammals, and non-human primates. Currently, the natural epidemiological history of monkeypox virus is unclear, and further research is needed to determine the exact animal host and how the virus spreads in nature.

In 2003, it was first reported in the United States that rodents from Ghana transmitted MPXV to pet prairie dogs in Illinois (see Figure 3), resulting in a clustered outbreak of infection in more than 70 residents. Later, monkeypox cases were reported in travelers from Nigeria to Israel (2018), to the United Kingdom (2018, 2019, 2021, 2022), Singapore (2019), and the United States (2021). Since May 2022, monkeypox cases have been detected in nearly 20 non-endemic countries, involving Europe, North America and the Middle East.

Figure 3. Prairie dogs

01 Source of infection

MPXV reservoirs and infected animals are the main sources of infection in humans. Humans are the sole host of variola virus, but MPXV reservoirs are broader, including rodents, mammals, and non-human primates, such as Kenyan vervet monkeys, chimpanzees, African elephants, wild boars, antelopes, Gambian giants Rat, marmot, West African squirrel, anteater, etc. The natural host of MPXV has not been identified, but rodents are the most likely.

Monkeypox patients or latent infections are an important source of infection for the monkeypox epidemic in the population. The incubation period for the onset of human monkeypox is usually 5 to 21 days.

Clinical manifestations can be divided into two stages. The invasive stage (0-5 days) is characterized by fever, severe headache, swollen lymph nodes, muscle pain, and severe weakness. , smallpox) distinguishing features. The rash stage usually occurs within 1 to 3 days after fever. Rashes tend to be more concentrated on the face and extremities, such as the face (95% of cases), palms and soles (75%), oral mucosa (70%), genitals (30%), and conjunctiva (20%). The rash ranges from macules (the lesions are flat at the base) to papules (the lesions are slightly raised and firmer), vesicles (the lesions are filled with clear fluid), pustules (the lesions are filled with yellow fluid), until the rash dries up and the crusts fall off.

Monkeypox is usually a self-limiting disease with symptoms lasting 2 to 4 weeks. Severe cases, mostly in children, are related to the degree of exposure to the virus, the patient's health, and complications. Historically, monkeypox case fatality rates have ranged from 0% to 11% in the general population.

The diagnosis of monkeypox patients depends on the type and quality of the specimen, as well as the hardware and software recommendations for laboratory testing. Polymerase chain reaction (PCR) is the preferred laboratory test. The best specimens for laboratory diagnosis of monkeypox are from the site of skin lesions—vesicles and pustules, or fluid, and crusts. Biopsy is an option when feasible. Blood samples are usually not used for diagnostic specimens. Because orthopoxviruses are serologically cross-reactive, antigen and antibody detection methods cannot provide a specific basis for the diagnosis of monkeypox.

02 Transmission route

Animal-to-human transmission that occurs when humans directly contact the blood, body fluids, diseased skin or mucous membranes of infected animals is called the primary case. MPXV can enter the human body through broken skin (even if unrecognizable), mucous membranes (eyes, mouth) and respiratory tract, but it is less efficient to transmit to humans in the form of respiratory droplets. Cases of infection through contact with the urine and feces of infected animals have also been reported. Eating undercooked meat from infected animals is also a contributing factor.

Human-to-human transmission is caused by contact or inhalation of the respiratory secretions, diseased skin or mucous membranes of infected persons, and contaminated environmental surfaces, which are called secondary cases. Transmission via respiratory droplets usually requires prolonged close face-to-face contact. Therefore, medical staff, family members and other close contacts are at high risk of monkeypox infection. The longest recorded community transmission chain is at least six generations. Transmission can also be through contact with virus-contaminated items, such as bedding and clothing. There have been reports of transmission from infected pregnant women to the fetus (congenital monkeypox cases). It is worth noting that the cases reported in some countries are concentrated in men between the ages of 20 and 50, many of whom are homosexuals. Although it is not known whether monkeypox is transmitted through sexual contact, sexual activity actually constitutes close physical contact.

Patients are infectious from the onset of disease (marked by fever), with shedding of infectious virus particles at various stages throughout the course of the disease until scabs fall off and new skin forms. The infectious period is about 4 weeks.

Using data from 1981 to 1986, the monkeypox R0 was 0.8.

03 Susceptible population

Epidemiological surveys show that people who have not been vaccinated with cowpox are generally susceptible to MPXV; the vaccinated people have a certain immunity to monkeypox, but with the passage of time, the level of antibodies decreases year by year, so there is a risk of infection. Human monkeypox can be prevented (85% protection rate) by vaccination with smallpox vaccine (vaccinia), and data show that the fatality rate of people who have not been vaccinated is 9.8%.

Historically, human-to-human transmission is uncommon and usually ends after 1 or 2 generations of transmission. Epidemiological investigations show that monkeypox has become an endemic disease in some African countries, and outbreaks have occurred from time to time.

Between 2005 and 2007, five laboratory-acquired cases of Vaccinia virus (VACV) infection were reported to CDC by state health departments and health care providers in the United States.

In September 2018, there was an incident of nosocomial infection of MPXV among medical staff in the United Kingdom, possibly through contact with contaminated bedding. To this end, the local health administration and disease control conducted an epidemiological investigation on the case and close contacts, conducted infection risk assessment and public health recommendations for each type of exposed person one by one, and implemented home isolation according to the degree of exposure. , medical monitoring, and post-exposure precautions.

"Prevention and Control"

Formulate emergency response plans for monkeypox, carry out business training for relevant personnel, improve the ability of infection risk assessment, and reserve laboratory diagnostic techniques as the main content of prevention strategies.

During human monkeypox outbreaks, close contact with an infected person is the most important risk factor for monkeypox virus infection. Medical staff and family members are at greater risk of infection. Persons caring for or handling specimens of patients with suspected or confirmed monkeypox virus infection should implement standard precautions and follow laboratory biosafety procedures.

Clinically suspected monkeypox cases, especially those with epidemiological exposure history, should take timely isolation measures, including contact isolation and droplet isolation measures.

Close contact with wild animals should be avoided, especially contact with sick or dead animals without personal protection.

Some countries have introduced regulations restricting the import of rodents and non-human primates. Captive animals suspected of being infected with monkeypox should be kept in isolation from other animals. Any animals that may have been in contact with infected animals should be quarantined for a medical observation period of 30 days.

Cowpox vaccine is 85% effective against monkeypox. Therefore, some high-risk personnel, medical personnel, port quarantine personnel and animal quarantine personnel can receive vaccinia vaccination according to the nature of their posts, the historical vaccination time of vaccinia, and the prevalence of local monkeypox. In 2019, a modified attenuated vaccinia vaccine (Ankara) was approved in the United States for the prevention of monkeypox as a two-dose vaccine. Based on the cross-protective effect of orthopoxviruses, both smallpox and monkeypox vaccines use vaccinia virus as the vaccine strain. Some countries have or are developing policies to provide vaccinations to high-risk groups.

In addition to vaccinia vaccination, clinical treatments for occupationally exposed persons include intravenous vaccinia immune globulin (VIG), intravenous cidofovir and oral tecovirimat.

"Environmental Surface Disinfection"

MPXV is a lipophilic DNA virus, which is sensitive to commonly used disinfectants and heat-sensitive. At 50°C (92.3%) or 56°C (100%) for 20 minutes, it almost partially or completely loses its infectivity.

Pustular swabs from patients with Variola virus (VARV) remained infectious for 8 weeks at 30-35°C, while vesicle contents remained infectious in culture for 9 months. Experiments show that the vaccinia virus strain (VACV) is sensitive to ultraviolet rays, and can inactivate VACV in drinking water under 254 nm UV irradiation for 20 s.

There are studies using vaccinia virus strain (VACV) and modified vaccinia Ankara strain (Modified vaccinia Ankara, MVA) to conduct parallel tests in 3 laboratories in Germany at the same time (all experiments use 10% fetal bovine serum intervention), the results The display is as follows.

50% ethanol: After 1min of VACV, the virus titer decreased by ≥4.38±0.37～≥5.94±0.31.

40% isopropanol: After 1min of VACV, the virus titer decreased by ≥4.38±0.37～≥5.94±0.31.

0.1% peracetic acid (PAA): After 1min of VACV, the virus titer decreased by ≥3.86±0.39～≥6.38±0.37.

50% ethanol: After acting on MVA for 1min, the virus titer decreased by ≥3.57±0.40～≥≥5.40±0.36.

40% isopropanol: After acting on MVA for 1min, the virus titer decreased by ≥≥3.57±0.40～≥≥5.40±0.36.

0.1% peracetic acid (PAA): After acting on MVA for 1min, the virus titer decreased by ≥≥≥3.94±0.47～≥≥5.19±0.43.

It can be seen that MPXV is very sensitive to the commonly used disinfectants. Therefore, you can refer to the "Notice on Comprehensive and Accurate Environmental Sanitation and Disinfection" issued by the State Council's Comprehensive Team of the Joint Prevention and Control Mechanism for the New Coronavirus Pneumonia Epidemic. According to the relevant provisions of the Guidelines for the Use of Common Disinfectants, the selection of environmental surface disinfectants is scientific and standardized, and the two most basic principles of "cleaning unit" and "effective reuse" are adhered to, and the pollution sources in the environmental surface are eliminated to the greatest extent possible. Recommended as follows:

?01 Environmental table: quaternary ammonium salt, alcohol + quaternary ammonium salt compound, alcohol, hydrogen peroxide, peracetic acid and other disinfection (sanitary) wipes; or chlorine-containing disinfectant (500mg/L ~ 1000mg/L) , hypochlorous acid (100mL～200mg/L), chlorine dioxide (50mg/L～100mg/L), peracetic acid (0.1%～0.2%), hydrogen peroxide (3%), bromine-containing disinfectant (bromine Chloro-5,5-dimethylhydantoin Total available halogen 200mg/L～400mg/L; 1,3-dibromo-5,5-dimethylhydantoin available bromine 400mg/L～500mg/L L), quaternary ammonium salt disinfectant (1000mg/L ~ 2000mg/L), etc., wipe and disinfect after cleaning rags and floor towels.

02 Fabrics such as bedding, patient clothes and daily clothes: It is recommended to use a washing machine with thermal disinfection function for cleaning and disinfection (see Figure 4), and implement the A0 value of 600 standard, 80℃×10min, 90℃×1min, 93℃×0.5min ; Manual cleaning implements WS/T 367 "Technical Specifications for Disinfection in Medical Institutions".

Figure 4 Medical thermal disinfection washing machine and dryer

03 Air disinfection: Hypochlorous acid (50mgL~200mg/L) spray, hydrogen peroxide atomization (concentration according to the manufacturer's instructions) disinfection, ultraviolet radiation disinfection, mobile air purification and disinfection machine (device), etc.

04 According to Annex 2 of the "Notice on Printing and Distributing the Work Plan for Medical Treatment of the New Coronary Pneumonia Epidemic in Autumn and Winter" (Joint Prevention and Control Mechanism Medical Development (2020) No. 276), cleaning and disinfection guidelines, cleaning and disinfection of medical fabrics should be made of waterproof fabrics. The bedding with antibacterial and dustproof function can be cleaned and disinfected by wiping.

? Main Reference

1. Malik YS and Singh R. Animal-Origin Viral Zoonoses. Springer Nature Singapore Pte Ltd. 2020.

2. Centers for Disease Control and Prevention (CDC). Laboratory-acquired vaccinia exposures and infections--United States, 2005-2007. MMWR Morb Mortal Wkly Rep. 2008;57(15):401-404.

3. Kozlov M. Monkeypox goes global: why scientists are on alert [published online ahead of print,

2022 May 20]. Nature. 2022;10.1038/d41586-022-01421-8. doi:10.1038/d41586-022-01421-8

4. Vaughan A, Aarons E, Astbury J, et al. Human-to-Human Transmission of Monkeypox Virus, United Kingdom, October 2018. Emerg Infect Dis. 2020;26(4):782-785. doi:10.3201/eid2604.191164

5. Rabenau HF, Rapp I, Steinmann J. Can vaccinia virus be replaced by MVA virus for testing virucidal activity of chemical disinfectants?. BMC Infect Dis. 2010;10:185. Published 2010 Jun 23. doi:10.1186/1471-2334-10-185

6. Abrah?o JS, Trindade Gde S, Ferreira JM, et al. Long-lasting stability of Vaccinia virus strains in murine feces: implications for virus circulation and environmental maintenance. Arch Virol. 2009;154(9):1551-1553. doi:10.1007/s00705-009-0470-1

7. Centers for Disease Control and Prevention (CDC). Laboratory-acquired vaccinia exposures and infections--United States, 2005-2007. MMWR Morb Mortal Wkly Rep. 2008;57(15):401-404.

8. Essbauer S, Meyer H, Porsch-Ozcürümez M, Pfeffer M. Long-lasting stability of vaccinia virus (orthopoxvirus) in food and environmental samples. Zoonoses Public Health. 2007;54(3-4):118-124. doi:10.1111/j.1863-2378.2007.01035.x

9. Eggers M, Eickmann M, Kowalski K, Zorn J, Reimer K. Povidone-iodine hand wash and hand rub products demonstrated excellent in vitro virucidal efficacy against Ebola virus and modified vaccinia virus Ankara, the new European test virus for enveloped viruses. BMC Infect Dis. 2015;15:375. Published 2015 Sep 17. doi:10.1186/s12879-015-1111-9

(1) YJC70115NW-50T. CE Certified Monkeypox Virus Real Time PCR Kit

The Bioperfectus Monkeypox Virus Real Time PCR Kit is based on real-time PCR technology, for the detection of DNA from the Monkeypox virus. Specimens can be obtained from human serum, lesion exudate samples and scab. BSL-2 facilities with standard BSL-2 work practices may be used for the test of the Monkeypox virus.

(2) VJC70115NW-50T. For Veterinary detection.

The Monkeypox Virus Real Time PCR Kit (Cat. No. VJC70115NW-50T) enables detection of the Monkeypox virus (MPXV) in serum, conjunctival swabs or tissue from animals including non-human primates (e.g., monkeys and apes), rodents (e.g., rats and squirrels), shrews (e.g., Crocidura spp.) and other small mammals (e.g., rabbits) with suspected MPXV infection by real-time PCR amplification of the MPXV F3L gene.