Monkeypox Response Guidelines

1. Introduction

Monkeypox (MPX) is a viral zoonotic disease with symptoms similar to smallpox, although with less clinical severity. MPX was first discovered in 1958 in colonies of monkeys kept for research, hence the name ‘monkeypox.’ The first human case of monkeypox was reported by the Democratic Republic of the Congo (DRC) in 1970.

Historically, monkeypox virus primarily occurred in Central and West Africa. In 2003, the first monkeypox outbreak outside of Africa was reported in the United States of America which 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.

1.1 Global Scenario

This is the first time that chains of transmission are reported in multiple continents without known epidemiological links to West or Central Africa. At the end of July 2022, monkeypox had already been reported across six continents and 80 countries with the largest number of cases in Spain, USA, UK, Germany, France, Netherlands, Brazil, Canada, Portugal, Italy, Belgium, Switzerland, Peru, and Israel.

Objective

Historical experience with monkeypox and smallpox indicates that it is possible to stop the monkeypox outbreak and eliminate transmission in areas outside of its historical context in West and Central Africa through effective surveillance and isolation as described in this guideline. Current epidemiological data on growth of the outbreak indicates that this action is needed to reduce R to be less than one, prevent wider spread, and achieve elimination. The robust way to be successful is to rapidly identify existing cases while their number is low. Rapid action will also reduce the risk of transmission to rodent populations in other areas that would become a persistent source of reintroduction in the future resulting in additional societal harm and disruption. Preventing wider transmission will also protect vulnerable populations including children, pregnant persons, and the immunocompromised, as well as prevent widespread painful and physiologically harmful infections in many others.

2. Epidemiology

2.1 Agent

Monkeypox virus (MPXV) is an enveloped double-stranded DNA virus that belongs to the Orthopoxvirus genus of the Poxviridae family. There are two distinct genetic clades of the monkeypox virus – the Central African (Congo Basin) clade and the West African clade. The Congo Basin clade has historically caused more severe disease and was thought to be more transmissible. The geographical division between the two clades has so far been in Cameroon – the only country where both virus clades have been found.

2.2 Host

The primary natural reservoir is not well known, but includes rodents (including rope squirrels, tree squirrels, Gambian pouched rats, dormice) and non-human primates (e.g monkeys) who are susceptible to monkeypox virus.

2.3 Incubation period

The incubation period (interval from infection to onset of symptoms) of monkeypox is usually from 6 to 13 days but can range from 5 to 21 days.

2.4 Period of communicability

1-2 days before rash onset until all the scabs fall off and are resolved.

2.5 Mode of transmission

There is evidence for human-to-human transmission through (1) direct physical contact with skin or lesion material, (2) indirect contact through contaminated clothing or bedding of an infected person, and (3) airborne transmission. 

Animal-to-human transmission: may occur by bite or scratch of infected animals like small mammals including rodents (rats, squirrels) and non-human primates (monkeys, apes) or through bush meat preparation.

3. Case Definition

3.1 Suspected Case

In a country with community outbreak: A person of any age presenting with:

1. An acute rash that has lesions that are deep-seated, painful, and well-circumscribed

OR 

2. Any rash

AND

one or more of the following signs or symptoms

•  Swollen lymph nodes
•  Fever
•  Headache
•  Body aches
•  Profound weakness

In a country without ongoing community outbreak: A person of any age having a history of travel to affected countries within the last 21 days and presenting with an unexplained acute rash.

3.2 Probable Case

A person, including a health care worker, meeting the case definition for a suspected case and has an epidemiological link (in the same room without appropriate PPE including N95/FFP2 or better respirator; direct physical contact with skin or skin lesions, including sexual contact; or contact with contaminated materials such as clothing, bedding, or utensils).

OR

A case which is laboratory confirmed for orthopox virus (by detection of sequences of viral DNA either by polymerase chain reaction (PCR) and/or sequencing).

3.3 Confirmed Case

A case which is laboratory confirmed for monkeypox virus (by detection of unique sequences of viral DNA either by polymerase chain reaction (PCR) and/or sequencing).

4. Surveillance Strategies

The aims of the proposed surveillance strategy are to rapidly identify cases and clusters of infections and the sources of infections as soon as possible in order to:

• a)  isolate cases to prevent further transmission
• b)  provide optimal clinical care
• c)  identify and manage contacts
• d)  protect frontline health workers
• e)  protect the most vulnerable including children, pregnant persons, and immunocompromised.
• f)  implement effective control and preventive measures based on the identified routes of transmission.
• g) implement targeted proactive vaccination strategy to prevent case progression, reduce case severity, and prevent transmission for individuals and groups at risk of exposure.

4.1 Surveillance Outline

• a)  Use standard case definitions in all areas and at all points of entry.
• b)  Even one case of monkeypox is to be considered as an outbreak. A detailed investigation by the Rapid Response Teams must be initiated.
• c)  Report any suspected case immediately to relevant local and national authorities.
• d)  Send the samples as per the guidelines to the designated laboratories.

4.2 Primary Actions Include:

a) Targeted surveillance for probable cases or clusters.

b) Initiate contact tracing and testing of symptomatic individuals after detection of a probable or confirmed case.

4.3 Core Surveillance Strategy

a) Hospital and Community health center based Surveillance: Health facility-based surveillance & testing – in dermatology clinics, STD clinics, general medicine, pediatrics, oral medicine, etc.

b) Targeted Surveillance:

• i)  Targeted intervention sites for underserved communities, high-risk essential workers, and homeless communities.
• ii)  Targeted intervention sites identified for men who have sex with men (MSM) 

4.4 Surveillance Actions

• a)  Engage in an effective communication campaign through all channels with information for the public, healthcare professionals, corporations, minority and underserved communities, public health and community institutions. Live broadcasts, recorded, graphic, and written information should be distributed through traditional media, public social media, and professional media. 
• b) Information to be provided in the communication campaign to include information about history, symptoms, current status, identification of risk and harm and the actions to be taken to prevent or reduce risk and harm, pointing to the specific actions needed by individuals to achieve these objectives, and reporting on progress as the outbreak is developing.
• c) Any person developing a rash should immediately self-report it together with a picture and response to questions for assessment through identified channels to a central system or to one of an identified and readily accessible set of local community based systems. Multiple ways to perform reporting designed for and promoting accessibility should be available, including both electronic and direct access at clinical testing sites. 
• c) Medical/epidemiological staff evaluate the rash and decide based upon case definition (Section 3) whether the individual should undergo testing and provide information to the individual about steps to be taken to safely undergo testing.
• d) Allowance should be made for individual circumstances that may require obtaining additional information, and associated accommodation, including medical, social, occupational, financial, citizenship, spoken language, or other information needed to enable or facilitate testing and support specific identified needs.
• e) Capabilities should be in place for immediate response including providing necessary information for suspected cases and performing contact tracing for probable or confirmed cases.
• f) Isolation facilities and support protocols for individuals should be available to respond to rapidly growing demand.
• g) Monitor reports, including the dynamics of rash reports and test results, centrally and perform evaluation of the outbreak including temporal and geographical aspects. Develop protocols for improvement of the response effort as the outbreak develops. Recognize that social and viral dynamics are linked and continuous improvement is necessary to overcome viral evolution and support social action over time.

4.5 Reporting

Reporting of cases to be done according to local health authorities.

4.6 Border Surveillance

Advisory for international passengers and surveillance at Airports, Land and Water border control is given in Appendix 2.

5. Clinical Features

Monkeypox usually resolves without specific medical care (“self-limited disease”), with the symptoms lasting from 2 to 4 weeks. Severe cases occur more commonly among children, immunocompromised, and pregnant individuals, and are related to patient health status, nature of complications, and extent of exposure. The extent to which asymptomatic infection occurs is unknown. The case fatality ratio of monkeypox has historically ranged from 3 to 11% in the general population and has been significantly higher among young children. The case fatality ratio has been around 3.6% in the West African clade from which the current global outbreak originated. Blindness may result from corneal infection. 

5.1 Common Symptoms and Signs

Early stage (Prodrome, 0-5 days): Classically, a prodrome precedes the rash, although these systemic symptoms may be absent or may occur concurrently or following emergence of the rash.

• Fever
• Swollen lymph nodes (lymphadenopathy)
  • Typically occurs with fever onset
  • Periauricular, axillary, cervical or inguinal
  • Unilateral or bilateral
• Headache, muscle aches, exhaustion
• Chills and/or sweats
• Sore throat and cough

Skin involvement (Rash)

• Usually begins within 1-3 days of fever onset, lasting for around 2-4 weeks
• Deep-seated, well-circumscribed and often develop umbilication
• Lesions are often described as painful until the healing phase when they become itchy (in the crust stage)
• Stages of rash (slow evolution)

• Enanthem- first lesions on tongue and mouth
• Macules starting from face spreading to arms, legs, palms, and soles (centrifugal
  distribution), within 24 hours
• The rash goes through a macular, papular, vesicular and pustular phase. Classic lesion is vesiculopustular
• Involvement by area: face (98%), palms and soles (95%), oral mucous membranes (70%), genitalia (28%), conjunctiva (20%). Generally skin rashes are more apparent on the limbs and face than on the trunk. Notably the genitalia can be involved and can be a diagnostic dilemma in sexually tranmitted infection (STI) population
• By 3rd day lesions progress to papules
• By 4th to 5th day lesions become vesicles (raised and fluid filled).
• By 6th to 7th day lesions become pustular, sharpy raised, filled with opaque fluid,
  firm and deep seated.
• May umbilicate or become confluent
• By the end of 2nd week, they dry up and crust
• Scabs remain for a week before falling off
• The lesion heals with hyperpigmented atrophic scars, hypopigmented atrophic
  scars, patchy alopecia, hypertrophic skin scarring, anogenital scarring, and contracture/deformity of facial muscles following healing of ulcerated facial lesions
• A notable predilection for palm and soles is characteristic of monkeypox

• The extent and severity of skin manifestation depends on vaccination status, age, nutritional status, associated HIV status, and other underlying health conditions.
• The total lesion burden at the apex of rash can be quite high (>500 lesions) or relatively slight (<25).

5.2 Differential Diagnosis

Varicella (chicken pox), disseminated herpes zoster, disseminated herpes simplex, measles, chancroid, secondary syphilis, hand-foot-and-mouth disease, infectious mononucleosis, molluscum contagiosum, HIV/AIDS.

5.3 Complications

•  Secondary infections
•  Pneumonia, sepsis, encephalitis
•  Corneal involvement (may lead to loss of vision)

6. Diagnosis

6.1 Personal Protective Equipment for Handling the Clinical Specimens

PPE to be donned before collecting the specimens should include — coveralls/gowns, N95/FFP2 or better respirator, face shield/safety goggles, hair/head covering such as surgical cap or bouffant cap, double pair of gloves (long cuff preferred), and shoe covers. Coverall/gown and glove combinations should overlap, covering surfaces of the arms that are likely to contact the patient and surroundings. Donning & doffing of PPE should be carefully performed as per the standard procedure in designated locations. Procedure for sample collection in Appendix 1. Instructions for sample packaging and transport as recommended by WHO.

6.2 Clinical Samples to Be Collected for Testing as per the Criteria in Box 1:

Box 1: Observation or Sample Collection from those with Exposure

Community Exposure OR Traveler from Region of Community Transmission

1. Asymptomatic

Observe for the development of any signs and symptoms for 21 days post exposure

If signs and symptoms develop, collect specimens as below

2. Symptomatic

According to laboratory capabilities samples should be taken of skin lesions, oropharyngeal swabs (OPS) and nasopharyngeal swabs (NPS), blood and urine (see also APPENDIX 1 and https://www.who.int/publications/i/item/WHO-MPX-laboratory-2022.1) 

Flocked Dacron or polyester swabs should be used (cotton swabs should be avoided). Depending on laboratory instructions, dry swabs or swabs submitted in viral transport medium (VTM) may be submitted.

Prodrome phase:

Oropharyngeal swabs (OPS) and Nasopharyngeal swabs (NPS) in dry plain tube [without any bacterial medium, and VTM only if according to laboratory instructions]

Blood collected in SSGT (4-5 ml) for IgM testing (nucleic acid testing from oropharyngeal swabs is preferred)

The following specimen types may be considered for research-based testing:

Blood collected in EDTA (2-3ml)

Urine in sterile urine container (3-5ml)

Rash phase:

Clear lesion images should be taken and included in report

Skin lesion samples should be collected from multiple sites:

Lesion roof sampled using scalpel or plastic scraper, or using vigorous swabbing, collected in plain tube.

Lesion fluid with intradermal syringe

Lesion base scrapings with sterile polyester swab collected in plain tube

Lesion crust in plain tube 

Other samples:

Oropharyngeal swabs (OPS) and Nasopharyngeal swabs (NPS) in dry plain tube [without any bacterial medium, and VTM only if according to laboratory instructions]

Blood collected in SSGT (4-5 ml) for IgM testing (nucleic acid testing from lesions or oropharyngeal swabs is preferred)

The following specimen types may be considered for research-based testing:

Blood collected in EDTA (2-3ml)

Urine in sterile urine container (3-5ml)

Recovery phase:

Blood collected in SSGT (2-3ml)

Urine in sterile urine container (3-5ml)

6.3 Confirmation of Monkeypox

For the confirmation of Monkeypox on the suspected clinical specimens (Box 2) all clinical specimens should be transported to the local or national laboratories for

Option A:

• a)  PCR for Orthopoxvirus genus [Cowpox, Buffalopox, Camelpox, Monkeypox] 
• b)  If specimen will show positivity for the Orthopoxvirus, it would be further confirmed by Monkeypox specific conventional PCR or real time PCR for Monkeypox DNA
• c)  Additionally, virus isolation and the Next Generation Sequencing of clinical samples(Miniseq and Nextseq) will be used for characterization of the positive clinical specimens

Option B:

• a)  PCR for Monkeypox or real time PCR for Monkeypox DNA
• b)  Additionally, virus isolation and the Next Generation Sequencing of clinical samples(Miniseq and Nextseq) will be used for characterization of the positive clinical specimens

7. Management

7.1 Principles of Management

•  Patient isolation
•  Protection of compromised skin and mucous membranes
•  Rehydration therapy and nutritional support
•  Symptom alleviation including pain management
•  Monitoring and treatment of complications

7.2 Patient Isolation

Isolation of the patient in an isolation room of the hospital, other facility or at home in a separate room with separate ventilation (see Sections 9.2.1-9.2.4)

Patient to wear a high quality N95/FFP2 respirator mask without exhalation valve when others enter the room, and avoid wearing a mask when alone

Skin lesions should be covered to the best extent possible (e.g. long sleeves, long pants, sheets) when skin treatment or cleansing is not being performed to minimize risk of contact with others

Isolation to be continued until all lesions have resolved and scabs have completely fallen off

7.3 Supportive Management of Monkeypox

Protection of compromised skin and mucous membranes

1. Skin rash
   1.  Clean with simple antiseptic
   2.  Mupirocin Acid/Fucidin
   3.  Cover with light dressing if extensive lesion present
   4.  Do not touch/scratch the lesions
   5.  In case of secondary infection consider relevant systematic antibiotics 
2. Genital ulcers
   1. Sitz bath
3. Oral ulcers
   1. Warm saline gargles/oral topical anti-inflammatory gel
4. Conjunctivitis
   1. Usually, self-limiting
   2. Consult Ophthalmologist if symptoms persist or there are pain/ visual disturbances

Rehydration therapy and nutritional support

1. Dehydration can occur in association with poor appetite, nausea, vomiting, and diarrhea
   1. Encourage oral fluids or oral rehydration solution (ORS)
   2. Intravenous fluids if indicated
   3. Encourage nutritious and adequate diet

Symptom alleviation

1. Fever
   1. Tepid sponging
   2.  Acetaminophen/Paracetamol (Tylenol) as required
2. Itching/Pruritus
   1. Topical Calamine lotion
   2. Antihistamines
3. Nausea and vomiting
   1. Consider antiemetics
4. Headache/malaise
   1. Adequate hydration and Acetaminophen/Paracetamol (Tylenol) 

Antiviral therapy

1. Consider indications for antiviral therapy based on disease severity, patient risk factors, and balancing the risks of therapy with potential benefits

7.4 Monitoring and Treatment of Complications

The patient should closely monitor for the appearance of any of the following symptoms during the period of isolation:

• 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 the healthcare facility / specialist.

8. Contact Tracing

8.1 Definition of a Contact

A contact is defined as a person who, in the period beginning with the onset of the source case’s first symptoms (prodrome period, prior to rash, or development of the rash, whichever is first), and ending when all scabs have fallen off, has had one or more of the following exposures with a probable or confirmed case of monkeypox:

• face-to-face exposure (including health care workers without appropriate PPE)
• direct physical contact, including but not limited to sexual contact
• contact with contaminated materials such as clothing or bedding

Because of the potential for indirect transmission either through surfaces or aerosols, individuals may be infected due to presence in the same space even if they have not had identified contact. Where transmission probability increases the definition of a contact may be extended to those who have been in a shared space over a period of time following the presence of a probable or confirmed case. 

8.2 Contact Identification

Cases can be prompted to identify contacts across household, workplace, school/nursery, sexual contacts, healthcare, houses of worship, transportation, sports, social gatherings, and any other recalled interactions.

8.3 Contact Monitoring

• a) Contacts should be monitored at least daily for the onset of signs/symptoms for a period of 21 days (either early symptoms or rash as per Section 5.1) from the last contact with a probable or confirmed case or their contaminated materials during the infectious period. In case of occurrence of fever or other early symptoms clinical/lab evaluation is warranted.
• b) Effective education regarding the importance of symptom reporting and isolation guidelines if symptoms develop should be provided in verbal, written, and pictorial resources, and confirmation of the understanding of key points should be made.
• c) Asymptomatic contacts should not donate blood, cells, tissue, organs or semen while they are under surveillance.
• d) Preschool children may be excluded from daycare, nursery, or other group settings.
• e) Quarantine is not necessary for contacts if compliance with daily monitoring is performed. Contacts can generally pursue normal daily activities but should be cautioned to avoid high risk activities including physical contact with others, and may choose to avoid meeting with others during this period as a precautionary measure.
• f) Workers, including health workers, who have unprotected exposure to patients with monkeypox or possibly contaminated materials do not need to be excluded from work duty if asymptomatic, but should undergo active surveillance for symptoms for 21 days.
• g) If new evidence indicates significant presymptomatic transmission, revise guidelines to quarantine contacts.

8.4 If any Symptoms in a Contact Are Reported

Upon report of any symptoms in a monitored contact:

• a) Contact should immediately be isolated and diagnostic testing performed (Section 6) 
• b) If monkeypox infection is confirmed further contact tracing should be performed for recent activities and their contacts entered into monitoring (Section 8.3)
• c) Upon negative test result, and resolution of symptoms without appearance of a rash, contact can return to non-isolated monitoring.

9. Risk Communication and Preventative Measures

Raising awareness of risk factors and educating people about the symptoms, the need to report symptoms, and measures they can take to reduce exposure to the virus is the main prevention strategy for monkeypox. There are number of measures that can be taken to prevent infection with monkeypox virus:

• Avoid contact with any materials, such as bedding, that has been in contact with a sick person.
• Isolate infected individuals from others.
• Practice good hand hygiene after contact with infected humans or animals. For example,washing your hands with an alcohol-based hand sanitizer or with soap and water. Note: Soap washes away but does not disinfect monkeypox virus.
• Use appropriate personal protective equipment (PPE) when caring for patients in healthcare settings and during home care. 

9.1 Reducing the Risk of Human-to-Human Transmission

Surveillance and rapid identification of new cases is critical for outbreak containment. During human monkeypox outbreaks, close contact with infected persons is the most significant risk factor for monkeypox virus infection. Healthcare workers and household members are at a greater risk of infection. Healthcare workers caring for patients with suspected or confirmed monkeypox virus infection, or handling specimens from them, should implement standard infection control precautions. Samples taken from people and animals with suspected monkeypox virus infection should be handled by trained staff working in suitably equipped laboratories. Patient specimens must be safely prepared for transport with triple packaging in accordance with WHO guidance for transport of infectious substances.

9.2 Infection Prevention and Control (IPC)

A combination of standard, contact, droplet, and airborne precautions should be applied in all healthcare settings when a patient presents with fever and vesicular/pustular rash. Note: Due to evidence that monkeypox virus can infect through microscopic breaks in skin, hand washing after contact should not be relied upon. Gloves are necessary during any contact with infected individuals or contaminated objects for adequate protection. (In areas of high community prevalence, gloves should become standard precautions.)

Clinical triage includes early recognition and immediate placement of patients in separate areas from other patients (source control). All individuals, including family members, visitors and HCWs should apply standard, contact, droplet and airborne precautions. 

9.2.1 Patient Isolation

Patients should be managed in isolation. Precautions should be taken to minimize exposure to surrounding uninfected persons. Doors should be kept closed. When the patient is being cared for, the patient should wear a high quality N95/FFP2 respirator mask over the nose and mouth—if tolerable to the patient—and any of the patient’s exposed skin lesions should be covered with a sheet or gown. 

Isolation rooms in hospitals and other healthcare facilities are designed for use when it is essential to prevent the spread of infectious diseases to keep patients, personnel, and visitors safe and healthy. An isolation room may be organized in other locations so as to prevent transmission through surfaces, bedding and clothing, and airborne particles. Protocols for safe cleaning of surfaces, fabrics, as well as the air are necessary so that the number of surface and airborne infectious particles is minimized making the risk of cross-infection with other people unlikely. This includes control of the quantity and quality of intake or exhaust air, maintaining different air pressures between the room and neighboring areas, diluting infectious particles with large air volumes, and air filtration. 

9.2.2 Ambulance Transfer

When a case has to be transported, the personnel accompanying the patient should wear PPE (long sleeved gown, N95 respirator mask, gloves, shoe covers, and goggles).

Follow established protocols to ensure adequate advance information is given to the hospital about the admission/transfer of a potentially infectious person.

Request the patient wear a high quality respirator mask (if tolerated) and advise on Respiratory Hygiene and Cough Etiquette.

If lesions are present, cover them with long sleeved clothing/pants or a clean sheet to minimize contact with others. In the ambulance use disposable linen if available.

The ambulance should be cleaned and disinfected before using it for other patients. After wearing PPE, surfaces (stretcher, chair, door handles etc.) should be cleaned with a freshly prepared 1% hypochlorite solution or equivalent. Follow laundry service instructions: e.g. carefully place reusable blankets in a sealed plastic bag without shaking or fluffing them, then put into a laundry bag and send for laundering clearly labeling it so that person in the laundry wears appropriate PPE before handling, or before opening the sealed plastic bag. Follow manufacturer’s instructions for cleaning/disinfecting reusable equipment in the ambulance. All masks and any waste contaminated with crusts, secretions, serum or body fluids should be disposed of as infectious waste in a yellow or red bag. If biohazard bags are not available, place a biohazard sticker on the bag.  In the ambulance, if the driver’s chamber is not separate, the driver should also use PPE.

9.2.3 Additional Precautions

PPE (disposable gown, gloves, N95/FFP2 respirator mask, eye goggles, shoe covers) should be donned before entering the patient’s room and used for all patient contact. All PPE should be disposed of prior to leaving the isolation room where the patient is admitted.

Hand hygiene (following standard steps of hand hygiene) should be performed after all contact with an infected patient and/or their environment during care.

Perform correct containment and disposal of contaminated waste (e.g., dressings) in accordance with Biomedical Waste Management guidelines (2016 & subsequent amendments) for infectious waste.

Use care when handling soiled laundry (e.g., bedding, towels, personal clothing) to avoid contact with lesion material.

Soiled laundry should never be shaken or handled in a manner that may disperse infectious particles on other surfaces or create aerosols.

Use care when handling used patient-care equipment in a manner that prevents contamination of skin and clothing.

Ensure that used equipment has been cleaned and reprocessed appropriately.

Ensure provisions are in place for cleaning and disinfecting environmental surfaces in thepatient care environment, paying particular attention to high touch surfaces.

Hospital disinfectant currently used for environmental sanitation may be used as perrecommendations for concentration, contact time, and care in handling. 

9.2.4 Infection and Prevention Control (IPC) at Home

Patients who do not require hospitalization may be managed at home under conditions where taking effective preventive measures and essential support is possible:

Due to the extended isolation for Monkeypox, lasting 2-4 weeks, and the need for precautions to avoid physical contact, droplet and airborne transmission, as well as providing care during an often painful experience, effective isolation at home is difficult both for household members and for individuals who are isolating by themselves. 

Patients should be isolated in a room or area separate from other housemates. Healthy household members should limit contact with the patient.

Patients should not leave the home except for medical care, and should not use public transit for medical care appointments.

No visitors aside from trained individuals involved in the care of the patient (with appropriate PPE) should be allowed at home.

The room with the patient should have separate ventilation, and HEPA air filtering or negative pressure, i.e. fresh air enters the room and stale air is directly evacuated to the outside, where others are not located—there should be no flow of air from the isolation room into the rest of the building.

Household members should wear PPE, including a high quality N95/FFP2 respirator mask, when in the presence of the patient or potentially contaminated materials.

Patients should wear a high quality N95/FFP2 respirator mask when others are in the same space. 

Skin lesions should be covered to the best extent possible (e.g., long sleeves, long pants) to minimize risk of contact with others.

Disposable gloves should be worn for direct contact, including for surface cleaning, touching or laundry of clothing or bedding, or treatment of lesions. Gloves should be disposed of after use.

Care should be used when handling soiled laundry to avoid direct contact with contaminated material.

Soiled laundry should not be shaken or otherwise handled in a manner that may disperse infectious particles.

Laundry (e.g., bedding, towels, clothing) may be washed with warm water and disinfecting detergent.

Contain and dispose of contaminated waste (such as dressings, bandages, gloves) in a biomedical waste disposable bag. Do not dispose of waste in landfills or dumps.

Proper hand washing with soap and water, and use of an alcohol-based hand rub, should be performed by the patient and other household members after touching lesion material, clothing, linens, or environmental surfaces that may have had contact with lesion material. 

Dishes and other eating utensils should not be shared. Soiled dishes and eating utensils should be handled while wearing PPE and carefully washed with warm water and dish washing soap.

Contaminated surfaces should be cleaned and disinfected with 70% alcohol or 1 tbsp of bleach per gallon of water. Where unavailable, standard household cleaning/disinfectants may be used in accordance with the manufacturer’s instructions.

Pets and domestic animals should be excluded from the patient’s environment.

9.2.5 Duration of Isolation Procedures

Isolation precautions should be continued until all lesions have resolved and a fresh layer of skin has formed. Affected individuals should avoid close contact with children, immunocompromised persons, and pregnant women until all crusts are gone.

10. Risk Communication

Risk communication includes providing public health advice through all media channels that target audiences use on how the disease transmits, its symptoms, preventive measures, and what to do in case of suspected or confirmed infection. This should be combined with targeting community engagement to the population groups who are most at risk, working closely with health care providers, including community health and STD clinics, and civil society organizations.

Risk communication should be informed by insights from social listening detecting public sentiment and should address in a timely fashion possible rumors and misinformation. Health information and advice should be provided avoiding any form of stigmatization of certain groups such as men who have sex with men (MSM).

The key measures that can be taken to prevent infection with monkeypox virus:

Isolate infected patients from others who could be at risk for infection.

Avoid contact with any materials, such as bedding, that has been in contact with a patient of monkeypox.

Use high quality N95/FFP2 respirator masks and gloves when in contact with any infected individual including when caring for them.

11. Vaccination for Monkeypox Prevention

11.1  Targeted (Ring) Vaccination Strategy

Vaccines approved for monkeypox can be effective at providing protection against or reducing the severity of monkeypox illness when properly administered before or soon after an exposure. Vaccination is also helpful when combined with isolation to reduce transmission risk and help control the outbreak. 

Historical studies suggest an 85% efficacy of existing vaccines that were originally developed for smallpox and approved for monkeypox. 

Implementation strategies involve targeted rather than mass vaccination because of potential side effects of the widely available live replication-competent virus vaccine ACAM2000 and limited availability of a reduced side effect risk vaccine JYNNEOS designed to be replication incompetent. As larger quantities of the JYNNEOS vaccine become available, mass vaccination approaches may be considered.

Prevention of symptomatic onset of monkeypox disease is possible with vaccinations given within 4 days of exposure. Between 4 and 14 days after exposure, vaccination may reduce severity of disease, but is not expected to prevent symptoms from occurring. 

There are three populations that may be vaccinated based upon vaccine availability and size of population groups: infected individuals identified early due to surveillance, contacts identified by contact tracing, and populations at a high risk of exposure.

Prioritizing groups for vaccination:

1. Individuals who are suspected or confirmed cases with symptoms or contact tracing history consistent with initial exposure within the past 14 days
2. Individuals who are identified as a high risk contact due to physical contact, including sexual contact, with a probable or confirmed  case in the past 14 days
3. Any individual who is identified by contact tracing as a contact of a probable or confirmed case in the past 14 days
4. Individuals who are members of high risk groups due to physical contact, including but not limited to sexual contact, with multiple individuals in the past 14 days in a community with high prevalence, i.e. men who have sex with men (MSM). 
5. Laboratory, health care or other workers who are in frequent contact with monkeypox contaminated materials or providing care to individuals with an identified case.  

11.2  Vaccine information (Adapted from https://www.cdc.gov/poxvirus/monkeypox/considerations-for-monkeypox-vaccination.html)

11.2.1 JYNNEOS 

JYNNEOS contains a live virus (MVA-BN) that does not replicate efficiently in human cells.

• It is administered as two subcutaneous injections four weeks apart.
• The immune response takes 2 weeks after the second dose for maximal development.
• The effectiveness of JYNNEOS against monkeypox is supported by animal studies.
• There are no data on the efficacy of JYNNEOS for the current outbreak.
• Adverse reactions include injection site reactions such as pain, swelling, and redness.
• People with a severe allergy to any component of the vaccine (gentamicin, ciprofloxacin, egg protein) should not receive this vaccine.
• Safe for administration to people with HIV, atopic dermatitis, and other skin disorders.
• While there is no data on people who are pregnant or breastfeeding, animal data do not show evidence of reproductive harm; current recommendations are that pregnancy and breastfeeding are not contraindications.
• On November 3, 2021, the US Advisory Committee on Immunization Practices (ACIP) voted to recommend JYNNEOS pre-exposure prophylaxis as an alternative to ACAM2000 for certain persons at risk for exposure to orthopoxviruses.
• It is licensed by the US FDA for prevention of smallpox or monkeypox in people ages 18 years and older. In the US use in younger populations requires submission of exception forms (single patient Expanded Access Investigational New Drug (IND) application).

11.2.2 ACAM2000

ACAM2000 is a live Vaccinia virus vaccine that is replication competent.

• It is administered as one percutaneous dose via a multiple puncture technique with a bifurcated needle.
• The immune response takes 4 weeks for maximum development.
• Following a successful inoculation, a lesion (known as a “take”) will develop at the site of the vaccination; the lesion may take up to 6 weeks or more to heal.
• Licensed by the US FDA for use against smallpox; allowed for use against monkeypox under an Investigational New Drug Expanded Access (IND), which requires informed consent along with submission of additional forms.
• The effectiveness of ACAM2000 is supported by human clinical trials and animal studies.
• There are no data on the efficacy of ACAM2000 for the current outbreak.
• Adverse reactions include injection site pain, swelling, and redness; fever; rash; lymph node swelling; and complications from inadvertent inoculation.
• People with severe allergy to any component of the vaccine should not receive it. In addition, people with severely weakened immune systems should not receive this vaccine.

ACAM2000 should not be given to people with the following conditions:

• Cardiac disease
• Eye disease treated with topical steroids
• Congenital or acquired immune deficiency disorders, including those taking immunosuppressive medications and people living with HIV (regardless of immune status)
• Atopic dermatitis/eczema and persons with a history of atopic dermatitis/eczema or other acute or exfoliative skin conditions
• Infants less than 12 months of age
• Pregnancy

When developing vaccine plans, consider the following approaches to ensure equitable distribution:

• Engage diverse partners already working with special populations
• Use non-stigmatizing language
• Reiterate privacy of information and how data will be used
• Bring vaccines to where people are through pop-up events and mobile outreach
• Engage people with lived experience in planning and through peer education models

11.2.3 Special Considerations for JYNNEOS 

Two doses of JYNNEOS are required by US guidelines, as this is the only FDA-approved dosing regimen.

JYNNEOS has been evaluated in clinical studies involving people with HIV infection and atopic dermatitis and shown to be safe and effective in eliciting an immune response in these populations.

People who receive JYNNEOS are considered to reach maximum immunity 14 days after their second dose (~ 6 weeks from first dose). They should continue to take precautions against monkeypox during this time.

We do not know if JYNNEOS will fully protect against monkeypox virus infection in this outbreak. Individuals wanting to minimize their risk of infection should take additional preventive measures and self-isolate as soon as they develop monkeypox symptoms, such as a rash. Infections despite vaccination may occur, and there is currently no data on effectiveness of JYNNEOS from the current outbreak.

11.2.4 Special Considerations for ACAM2000

Adverse events following ACAM2000, including myopericarditis or Vaccinia virus transmission to household contacts, can be serious. In the US ACAM2000 wil be made available for individuals who decide in consultation with their healthcare provider that the potential benefits of vaccination outweighs any potential risks from ACAM2000 adverse events.

Recipients should be informed of the risks and benefits of ACAM2000 prior to vaccination. People who are eligible for and offered ACAM2000 should be tested for HIV to ensure they are HIV negative, counseled on potential side effects, and sign an informed consent. Recipients should be advised to keep the vaccination site covered and to avoid swimming, sharing of blankets and towels, and contact with people who might be at risk for serious adverse events, such as people with weakened immune systems, atopic dermatitis/eczema, children younger than 12 months, or people who are pregnant.

Providers should advise the vaccine recipient on how to keep the vaccination site clean and covered until the lesion completely heals (up to 6 weeks or more). Providers should be properly trained on administration of ACAM2000 using a bifurcated needle and should follow up with the patient to assess the vaccination site for a vaccination “take.”

Any provider can administer ACAM2000; training may be obtained online through a CDC training video.

People who receive ACAM2000 are considered to reach maximum immunity ~ 1 month after their dose. Until full immunity is reached, they need to take specific precautions to prevent spread of the vaccine virus to others, including through direct contact (including sexual contact).

Since there is currently no data on the effectiveness of ACAM2000 from the current outbreak, people who get this vaccine should continue to take steps to protect themselves from infection even after vaccination takes full effect.

How previous smallpox vaccination may affect current recommendations for JYNNEOS

• Previous smallpox vaccination does provide protection, but it may not necessarily be lifelong. During the 2003 US monkeypox outbreak and during the current outbreak, several people who were infected with monkeypox had previously been vaccinated against smallpox decades prior.
• In response to an outbreak, vaccines and other medical measures would also be given to eligible people who were previously vaccinated against smallpox.
• The US Advisory Committee on Vaccination Practices (ACIP) provides guidance for revaccination for those at occupational risk of exposure.

Appendix 1: Procedures for the Clinical Specimen Collection

(see also https://www.who.int/publications/i/item/WHO-MPX-laboratory-2022.1):

• Appendix 1: Procedures for the clinical specimen collection (see also https://www.who.int/publications/i/item/WHO-MPX-laboratory-2022.1):
  • Nasopharyngeal and Oropharyngeal swabs in screw capped plain tube:
    •  Explain the procedure to the patient
    •  Remove the polystyrene swab. Don’t let anything touch the sterile swab on the end of the stick
    •  Ask patient to open mouth and stick their tongue out
    •  Use tongue spatula to press the tongue downward to the floor of the mouth.
    •  Use sterile polystyrene swab to swab both of the tonsillar arches and the posterior nasopharynx, without touching the sides of the mouth.
    •  Reach behind the uvula and swab: a. tonsillar fauces, b. the posterior pharynx, and c. any ulceration, exudate, lesion, or area of inflammation.
    •  Don’t let the sterile swab touch the patient’s tongue, gums, or teeth as you gently remove it from his/her mouth
    •  Place the swab into the screw-capped plain plastic tube [without any medium or VTM]
    •  Similarly, tilt the patient’s head back 70 degrees. Gently and slowly insert a polystyrene swab with a flexible shaft through the nostril parallel to the palate until resistance is encountered.
    •  The distance is equivalent to that from the nostril to the ear of the patient, indicating contact with the nasopharynx
    •  Gently rub and roll the swab, leaving it in place for several seconds to absorb secretions. If a deviated septum or blockage creates difficulty in obtaining the specimen from one nostril, use the same swab to obtain the specimen from the other nostril
    •  Slowly remove the swab while rotating it. Specimens can be collected from both nostrils
    •  Place the swab into the same screw-capped plain plastic tube [dry swab without any medium or viral transport medium (VTM)] in which the OPS swab was kept
    •  Break the excess stick and recap the tube tightly.
    •  Keep the tube in an upright position in the stand.
    •  Surface decontaminate the tube using 2% Lysol (Benzalkonium chloride) or 0.5-1% Sodium hypochlorite wipes
  • Venous Blood Collection in SSGT and EDTA tube:
    •  Explain the procedure to the patient
    •  Check the patient’s fore-arm/median cubital fossa for a prominent vein of good size. Use the median cubital vein wherever feasible.
    •  Apply the tourniquet 4-5 fingerbreadths above the site of venipuncture.
    •  Perform hand hygiene by using an alcohol-based hand rub on the outer pair of gloves.
    •  Disinfect the skin site using a wipe containing 70% alcohol, in a circular motion, from the center to periphery. Allow the skin to dry.
    •  Do not re-touch the puncture site. In case of accidental touch, repeat the skin disinfection as above.
    •  Anchor the vein by holding your thumb below the puncture site.
    •  Ask the patient to make a fist so as to make the veins prominent.
    •  Insert the needle (vacutainer or syringe needle) into the vein, bevel side up, at an angle of about 300 and advance the needle into the vein.
    •  Collect5mLofblood(intothesyringeorintotubes)andaliquot2mlinEDTA(Purple top) 3 ml in SSGT (Yellow top) for serum separation.
    •  Release the tourniquet
    •  Withdraw the needle gently and apply a piece of sterile gauze to the puncture site
    •  Ask the patient to gently press down on the gauze on the puncture site, keeping the arm folded
    •  If a syringe and needle were used for collection, transfer the blood inside the tube by piercing the stopper of the tubes placed firmly on a rack.
    •  Invert EDTA tubes gently 4-5 times to ensure proper mixing of the additives
    •  Keep the tubes in an upright position in the stand.
    •  Discard the syringe and needle into the sharps container
    •  Surface decontaminate the SSGT and the EDTA tube using 2% Lysol or 0.5-1% Sodium hypochlorite wipes
  • Urine sample collection in the screw capped sterile urine container:
    •  Explain the procedure to the patient
    •  Provide privacy to the patient
    •  First ask patient to wipe/clean the genitals
    •  Ask the patient to urinate a small amount into the toilet bowl, and then stop the flow of urine.
    •  Then collect a sample of urine into the clean or sterile container provided
    •  Ask the patient to collect about 3 to 5 mL of mid-stream urine sample into the
      collection tube provided, taking care not to contaminate the outside of the container
    •  Ask patient to finish urinating into the toilet bowl
    •  Close the lid carefully and keep the container standing position
    •  Surface decontaminate the SSGT and the EDTA tube using 2% Lysol or 0.5-1% Sodium hypochlorite wipes
  • Lesion roof, base scrapping, fluid and crust/scab collection [collect from multiple sites]:
    •  Explain the procedure to the patient
    •  Sanitize the skin covered with lesion with 80% alcohol wipes to start the collection
    •  Remove the lesion roof using sterile scalpel or plastic scraper
    •  Place the roof in the screw cap plain tube
    •  Similarly, use 1ml intradermal syringe to collect the pustular/vesicular fluids from multiple lesions and collect in fresh screw cap plain tube
    •  Use the polystyrene swab to collect the scrapings from the base of the lesions by gentle scraping and put it in fresh screw cap plain tube
    •  The scab/crust if formed using polystyrene swab, should also be collected in fresh screw cap plain tube
  • Procedures for the transport of the clinical specimens:
    •  Keep the samples immediately in +4 degree Celsius as soon as they are collected
    •  After collection of samples, appropriately labeled sample tubes need to be sealed with parafilm
    •  Centrifuge the serum tube before shipment
    •  Tubes need to be wrapped with the absorbent tissue paper/cotton and paced in Zip lock bags/Secondary receptacle
    • Samples should be transported in dry ice as per the instruction provided in Annexure- 3 (adapted from the WHO Guidance on regulations for the transport of infectious substances 2021-2022) along with the case record form provided with this document

Appendix 2: Advisory for Cross Border Passengers and Border Control 

Travelers should notify health facilities if:

• You develop symptoms suggestive of monkeypox like fever with rash
• You had contact with a person that might have had monkeypox
• You traveled from an area where monkeypox has been reported to an area where there is no community transmission

Travelers should AVOID:

• Close contact with sick people, including those with skin lesions or genital lesions
• Contact with contaminated materials used by sick people (such as clothing, bedding, or materials used in healthcare settings) or that came into contact with infected animals
• Contact with dead or live wild animals such as small mammals including rodents (rats, prairie dogs, squirrels), and non-human primates (monkeys, apes)
• Eating or preparing meat from wild game (bushmeat) or using products derived from wild animals from Africa (creams, lotions, powders)

Role of border control authorities:

• Familiarize with clinical presentation of monkeypox
• Remain in a state of alert, particularly for the passengers arriving from countries reporting monkeypox outbreaks
• Undertake strict thermal screening, history of travel, and risk status, to affected countries in last 21 days
• Establish/strengthen referral arrangements from airport/port to identified hospital.
• Familiarize Bureau of Immigration personnel, airline personnel and any State Health personnel deployed at the border facility about the disease
• Inform concerned airlines about detection of a suspect case for the purpose of disinfection procedure to be followed as per standard guidelines