Approach

Management strategies depend on disease severity and focus on the following principles:

  • Infection prevention and control

  • Symptomatic treatment

  • Optimised supportive care

  • Management of skin lesions

  • Management of complications

  • Antiviral therapy.

Patients benefit from supportive care and pain control that is implemented early in the disease course. However, this may not be adequate in some patients (e.g., immunocompromised patients), and antiviral therapy may be required.[86]

There is a lack of high-quality evidence-based clinical management guidelines to guide clinical decision-making. Recommendations across guidelines vary, and there are limited recommendations for different risk groups and complications.[154] The recommendations in this section are mainly based on guidelines from the World Health Organization (WHO) and apply to patients with suspected or confirmed infection.[22]

Infection prevention and control

Immediately contact your regional infectious disease unit if there is a clinical suspicion of infection.

  • This will trigger procedures to be activated for the safe transfer of the patient to a negative-pressure isolation facility and the notification of the public health team.

  • It is important to keep records of everyone who has been in close contact with the symptomatic patient (e.g., household contacts, paramedical and medical staff) and whether there are any potential animal carriers present.

  • All suspected or confirmed cases should be managed by experts, including public health officials, to prevent a potential emergency situation.

Follow your local infection prevention and control protocols.[22]

  • Standard, contact, and droplet precautions are recommended.

  • Airborne precautions are recommended when caring for suspected cases of monkeypox if chickenpox is suspected and until it is excluded. Respirators are recommended when caring for patients with confirmed monkeypox. Airborne precautions are recommended if aerosol-generating procedures are performed.

  • Treat all contaminated materials (e.g., linens, hospital gowns) and body fluids/solid waste of patients as potentially infectious.

Ideally all personnel likely to be in contact with the patient, bodily fluids, or fomites should have been vaccinated with the smallpox vaccine.[112] 

  • Post-exposure vaccination may be recommended for unvaccinated contacts (see Prevention).

  • Healthcare workers who are pregnant or severely immunocompromised should not assess or care for patients with suspected or confirmed infection, where possible.[113]

Mild or uncomplicated disease

Most cases are mild and self-limited and patients recover generally within 2 to 4 weeks.

Patients with suspected or confirmed infection and with mild or uncomplicated disease and who are not at high risk for severe or complicated disease may be isolated at home for the duration of the infectious period, provided that a home assessment determines that infection prevention and control conditions can be met in the home setting.[22]   

  • Make decisions on a case-by-case basis. Base decisions on factors such as clinical severity, presence of complications, patient care needs, nutrition and hydration status, risk factors for severe disease, and access to medical care if condition deteriorates. Patients should be ambulatory, have good water and food intake, and be able to manage their self-care.

  • Consider admission to a health facility for patients who are at higher risk of severe disease (e.g., children, pregnant women, immunocompromised people, people with skin conditions) for closer monitoring. Also consider admitting patients who live with vulnerable populations where adequate infection prevention and control precautions cannot be met.

  • Follow-up should be conducted using telemedicine or telephone where possible.

  • It is important that the patient follows their regional home self-isolation guidelines. See Patient discussions.

In the UK, the UK Health Security Agency (UKHSA) recommends that possible or probable cases may self-isolate at home, based on an assessment by the clinician and following UKHSA guidance. Possible or probable cases with a travel history to West or Central Africa may need to be managed as having a high consequence infectious disease (HCID); discuss with the Imported Fever Service.[114]

  • Assess all confirmed (or highly probable) cases for the need for admission based on either clinical or self-isolation requirements, and notify the local health protection team.

  • Admit patients who require hospital admission for clinical reasons, or those for whom self-isolation is not possible for social or medical reasons following clinical assessment, to a single room at a negative or neutral pressure at a local hospital site with respiratory protective equipment and personal protective equipment (with appropriate infection prevention and control).

  • NHS England recommends using a risk-stratified clinical approach (i.e., severe disease or infection in those with underlying risk factors for severe disease, risk to others or with other clinical complications requiring hospitalisation, lowest risk suitable for self-isolation at home) to aid these decisions. The specific current outbreak clade of monkeypox virus (Clade IIb) is no longer classified as an HCID in the UK.[134]

Appropriate symptomatic treatment (with attention to pain control) and supportive care are recommended.[22]

  • Pain

    • Pain management is an important part of treatment as pain is common and may be severe (e.g., rectal pain/proctitis, pain from lesions, pain from mucosal lesions not evident on physical examination, pain from lymphadenopathy, headache, muscle aches). Topical and/or systemic therapies may be required. Pain management strategies should be individualised, patient-centred, and tailored to the needs and context of an individual patient.[155] Assess pain initially, and then regularly assess pain control and adjust pain management as required. Consultation with a pain specialist may be required for refractory cases.

    • Over-the-counter medications such as paracetamol or ibuprofen are recommended for mild pain.[22][155] 

    • Opioids such as tramadol or morphine are recommended for the short-term management of severe pain (e.g., severe rectal pain due to proctitis) after an assessment of the benefits and risks associated with opioid use (e.g., constipation, opioid use disorder with long-term use).[22][155] 

    • Neuropathic pain agents (e.g., gabapentin) have been used for the short-term management of pain in some circumstances (e.g., severe proctitis) based on anecdotal reports.[155]

    • Salt water rinses, antiseptic mouthwashes (e.g., chlorhexidine), and local anaesthetics (e.g., viscous lidocaine) are recommended for oral lesions.[22][155]

    • Warm sitz baths and/or topical lidocaine are recommended for genital or anorectal lesions. Topical corticosteroids may also be used for genital lesions; however, the risks and benefits of using these agents on active lesions must be considered.[22][155]

    • Early treatment with the antiviral tecovirimat (see Antiviral therapy below) may help with pain control in patients with severe proctitis, based on case reports.[156] However, there is no evidence to support this.

  • Proctitis

    • Pain may be severe and require appropriate pain management (see above).

    • Corticosteroid/local anaesthetic suppositories or topical lidocaine gel may be used to relieve pain, spasm, and inflammation.[155][157]

    • Stool softeners may be considered to reduce pain associated with bowel movements (particularly if the patient is on opioid analgesia).[155][157]

    • Specialist referral is recommended for complications of proctitis (e.g., acute prostatitis, prostate abscess) as antibiotics may be required.[157]

  • Fever

    • Paracetamol is recommended for the management of fever.[22]

  • Pruritus

    • An antihistamine (e.g., loratadine) is recommended for the management of rash-associated pruritus. Topical agents such as calamine lotion, petroleum jelly, or colloidal oatmeal may also be considered.[22][155]

  • Nausea/vomiting

    • May be treated with anti-emetics (e.g., ondansetron, promethazine).[22]

  • Diarrhoea

    • Manage conservatively; anti-motility agents are generally not recommended.[22]

  • Dyspepsia

    • May be treated with a proton-pump inhibitor (e.g., omeprazole).[22]

  • Nutrition

    • Nutrition and hydration status may be compromised due to oropharyngeal lesions or painful cervical lymphadenopathy.[22]

    • Advise patients to maintain adequate hydration and nutrition. If this is not possible, evaluate the reason why (e.g., pain, nausea, weakness) and manage appropriately (e.g., analgesia, anti-emetic).

    • Provide vitamin A supplementation according to standard recommendations as it aids wound healing and eye health.

  • Mental health care

    • Promptly identify and assess for anxiety and depressive symptoms in order to initiate basic psychosocial support strategies and first-line interventions for the management of new anxiety and depressive symptoms (e.g., self-management strategies, psychological or pharmacological therapies).[22]

    • Psychosocial support strategies are recommended for the management of sleep issues (e.g., sleep hygiene advice).

A conservative approach to the management of skin lesions is recommended, with the aim to relieve discomfort, speed healing, and prevent complications. However, the optimal management of skin lesions is uncertain.[22] 

  • Advise patients not to scratch the skin, and to keep the skin lesions clean (i.e., with sterile water or antiseptic solution) and dry. The rash should not be covered. Avoid the use of plasters.

  • Monitor lesions for secondary bacterial infection (e.g., erythema, warmth, induration, worsening pain, purulent or malodorous discharge, recurrence of fever) and, if present, treat with appropriate oral antibiotic therapy.

    • The decision to initiate antibiotic therapy and choice of antibiotic should be based on individual clinical assessment and local antimicrobial resistance patterns. Follow your local protocols.

    • Prophylactic antibiotics are not recommended. Evidence on use of antibiotics for prophylaxis against secondary skin infections is anecdotal and limited.[5] Despite this, some centres may use topical antibiotics for prophylaxis in select patients (e.g., lesions on anogenital region, immunocompromised).[158]

  • Hospital admission may be required for a small proportion of patients with painful or infected skin or mucosal lesions for pain management and/or antibiotic therapy.[126] See section below.

  • Consider specialist referral if there is suspicion of exfoliation or deeper soft-tissue infection.

Monitor patients for deterioration of their clinical condition.[22]

  • Advise patients about signs and symptoms of complications that should prompt urgent care (e.g., lesions get worse or increase in quantity, worsening pain, persistent fever, decreased oral intake, visual symptoms, difficult breathing, dizziness, confusion).

Severe or complicated disease or patients at high risk of severe disease

Patients with severe disease, or those who are at increased risk of severe disease, typically require hospitalisation, supportive care, and antiviral therapy.

  • The patient will be transferred to a specialised centre for further care if hospitalisation is required.

  • For more information on patients who meet criteria for severe or complicated disease, or those who are at increased risk of severe disease, see Diagnosis approach.

Patients may require hospital admission for the management of pain and swelling, difficulty swallowing (odynophagia), eye lesions, or complications (e.g., bacterial superinfection).

  • Data from the current ongoing outbreak indicate that approximately 7% to 13% of cases required hospital admission for clinical reasons, usually for severe anorectal pain and proctitis, severe penile oedema, soft-tissue superinfection, pharyngitis limiting oral intake, or eye lesions. No serious complications were reported in the majority of those admitted. However, rare complications such as epiglottitis, tonsillitis, peritonsillar cellulitis, tonsillar/peritonsillar abscess, paraphimosis/phimosis, balanitis, perianal/groin abscess, rectal perforation, urinary retention, urethritis, encephalitis, and myocarditis have been observed.[7][44][54][118][119][133][159]

Admit patients with severe or complicated disease, or those who are at high risk for severe disease or complications, to hospital for closer monitoring and clinical care. Follow your local protocols.[22]

  • Monitor vital signs, neurological status, volume status, respiratory system, and signs of perfusion.

  • Monitor laboratory values including full blood count, urea and electrolytes, and liver function.

  • Assess pain, general condition, nutrition status, and rash characteristics (i.e., stage, location, number of lesions, presence of exfoliation or secondary bacterial infections).

  • Provide symptomatic treatment as necessary (see Mild or uncomplicated disease above).

Manage patients with optimised supportive care interventions. Follow your local protocols.[22]

  • Pay attention to fluid balance, oxygenation, nutrition, symptom relief (see Mild or uncomplicated disease above), prompt treatment of additional secondary bacterial infections, and management of complications and prevention of long-term sequelae.

  • Intravenous or intraosseous fluids, given as one or multiple boluses with close monitoring of fluid responsiveness, are recommended for the management of severe dehydration caused by intravascular volume loss.

  • Enteral nutrition may be required if the patient is unable to tolerate oral nutrition.

  • Pharmacological treatment may be required if the patient is agitated and becomes a danger to themself, other patients, or healthcare workers.

  • For specific information on how to manage complications, see Complications.

Consider antiviral therapy in patients who are at risk for severe or complicated disease or those who present with, or develop, severe disease.[22][86]

  • See Antiviral therapy section below.

Antiviral therapy

Antiviral agents developed for the treatment of smallpox (e.g., tecovirimat, brincidofovir, cidofovir) have activity against monkeypox virus and may be beneficial.[146][160]

Antiviral therapy is recommended in patients with severe or complicated disease, those who are at increased risk of severe disease or complications, those who have involvement of anatomical areas that might result in serious sequelae that include scarring or strictures (e.g., pharynx, penile foreskin, vulva, vagina, urethra, rectum, anus), or those who have severe infections (especially those that require surgical intervention such as debridement). Treatment should be started early in the disease course. However, there are no safety and efficacy data in humans to support the use of antiviral therapy for this indication.[22][86]

  • Tecovirimat is generally recommended as the first-line treatment.[86]

    • It is approved in the UK and Europe for the treatment of monkeypox based on animal and human studies. In the UK, it may be offered to symptomatic patients who have been admitted to hospital with severe or complicated infection. Supply is being managed via specialist regional adult infectious diseases centres.[161] 

    • It is approved in the US for smallpox, but may be used under an expanded access investigational new drug protocol for the treatment of monkeypox during an outbreak.

  • Alternative antivirals that may be approved or recommended for smallpox (e.g., brincidofovir, cidofovir) may be used off-label for monkeypox in some countries according to guidance from local public health authorities.

These drugs may be stockpiled in some countries, but are not yet widely available.

  • It is preferable to use antivirals under randomised clinical trials with collection of standardised clinical and outcome data. If this is not possible, antivirals may be used under expanded access protocols.[22]

  • Consult your local public health authority for guidance on the use of antiviral therapy.

Discontinuation of isolation precautions and discharge

Decisions regarding discontinuation of isolation precautions depend on whether the patient is hospitalised or self-isolating in a household setting, and should be made in consultation with the local public health authority.[162]

  • In general, precautions should be continued until all lesions have resolved and a fresh layer of skin has formed.

  • Prolonged upper respiratory tract viral shedding and viraemia after skin lesion resolution has been reported in a small number of patients, leading to extended isolation in hospital.[163]

In hospitalised patients, the UKHSA recommends that isolation precautions may end when the following criteria are met:[164]

  • Clinical criteria: the patient is judged to be clinically well enough for safe de-isolation as judged by the clinical team managing the patient

  • Laboratory criteria: the patient tests negative on polymerase chain reaction for all three of the following samples:

    • Urine

    • Throat swab

    • Ethylenediamine tetra-acetic acid (EDTA) blood (it is acceptable not to send EDTA blood if no sample was sent previously as the patient was well throughout admission)

  • Lesion criteria: there have been no new lesions for 48 hours; there are no mucous membrane lesions; and all lesions have crusted over, scabs have dropped off, and intact skin remains underneath.

Patients can be discharged from an isolation facility/ward to another hospital ward, a different inpatient facility, or a residential facility (e.g., care home) only when all of the above clinical, laboratory, and lesion criteria are met. Patients can be discharged to their home, without the need for ongoing isolation, if all of the above criteria are met. Patients who meet the clinical criteria, but who do not meet either the laboratory or lesion criteria, may be discharged to continue isolation at home (according to current public health regulations) where it is safe to do so as assessed by the treating clinician.

In household settings, the UKHSA recommends that patients are able to end self-isolation at home once the following criteria are met:[164]

  • Clinical criteria: the patient has been assessed by telephone or video call and has been afebrile for 72 hours and is considered systemically well

  • Lesion criteria: there have been no new lesions for 48 hours; there are no oral mucous membrane lesions; all lesions have crusted over; all lesions on exposed skin (including face, arms, and hands) have scabbed over, the scabs have dropped off, and a fresh layer of skin has formed underneath; and lesions in other areas can remain covered throughout the patient’s time outside of their home or when in contact with other people.

The patient can resume full normal activities with no restrictions (full de-isolation) when they meet the clinical criteria above and the following lesion criteria:[164]

  • No new lesions for 48 hours

  • No mucous membrane lesions

  • All lesions (for both exposed and unexposed areas) have crusted over, all scabs have dropped off, and intact skin remains underneath.

Advise patients to avoid close contact with immunocompromised people, pregnant women, and children <12 years of age until they meet full de-isolation criteria above (this may include exclusion from work if their work requires close contact with any of these groups).

Children and adolescents

Consider treatment on a case-by-base case in children and adolescents. Management is generally the same as for adults, with a few exceptions.[74]

  • Take the child’s age, caregiving needs, and family and carer preferences into consideration for isolation and infection control in children who require hospitalisation. Limit the number of carers to one person, when possible, regardless of whether the child is in hospital or at home.

  • Pay particular attention to keeping skin lesions covered and preventing children from scratching lesions or touching their eyes.

  • Tecovirimat is also the recommended first-line antiviral agent in children and adolescents, if treatment is indicated. However, safety and efficacy data are lacking and no clinical studies have been performed in paediatric populations. Alternative antiviral agents (e.g., cidofovir, brincidofovir) are reserved for unusual circumstances (e.g., very severe infections, disease progression despite tecovirimat treatment, tecovirimat is contraindicated or unavailable) due to their potential toxicity.

Pregnant and breastfeeding women

Prioritise pregnant (or recently pregnant) and breastfeeding women for treatment due to the probable increased risk for severe disease during pregnancy and the risk of transmission to the fetus or newborn baby.[76]

  • Discuss the risks and benefits of treatment with the patient using shared decision-making.

  • Closely monitor the patient for severe disease and pregnancy complications.

Pregnant (or recently pregnant) women with mild or uncomplicated disease may not require hospitalisation; however, close monitoring in a health facility may be preferred. Admit pregnant women with severe or complicated disease to a health facility for optimised supportive care and/or interventions to improve maternal and fetal survival.[22]

  • Method of delivery should be individualised, based on obstetric indications and the woman’s preferences. Induction of labour and caesarean section should only be undertaken when medically justified and based on maternal and fetal condition.

  • Monitor newborn infants closely for evidence of potential congenital or perinatal exposure or infection.

  • It is currently unknown whether the virus or antibodies are present in the breast milk of an infected mother. Infant feeding practices should be assessed on a case-by-case basis, taking the mother’s physical status and severity of disease into consideration.

  • General infection prevention and control measures are recommended for mothers when handling and feeding their infants (e.g., hand hygiene, wearing a mask if possible, covering any lesions that have direct contact with the infant).

Antiviral therapies should be used with caution in pregnant (or recently pregnant) and breastfeeding women, and only under the guidance of a local public health authority due to limited data in this population.

  • Tecovirimat is recommended first line in pregnant (or recently pregnant) and breastfeeding women, if treatment is indicated. However, there are no available data on human use during pregnancy or breastfeeding and the recommendation is based on animal studies (no embryo-fetal developmental toxicity was observed in animal studies).[76]

  • Cidofovir and brincidofovir have shown evidence of teratogenicity in animal studies and should not be used during the first trimester of pregnancy or in breastfeeding women.[76]

Further guidelines for the management of pregnant women have been proposed.[165][166]

HIV infection

Patients with HIV infection may be at increased risk of severe disease, and treatment and close monitoring is a priority in these patients.[81][82]

  • Continue antiretroviral therapy (including pre- or post-exposure vaccination) and opportunistic infection prophylaxis while managing monkeypox, as treatment interruption could lead to rebound viraemia, which could complicate the disease course.

  • Always check for drug-drug interactions between antivirals used for the treatment of monkeypox and antiretroviral therapy (or other treatments) for HIV infection.

The British HIV Association does not currently recommend any specific actions for people with HIV infection beyond vigilance about clinical presentation and history of exposure (except vaccine considerations). People with a CD4 count <200 cells/mm³, persistent viraemia (e.g., >200 copies/mL), recent HIV-related illness, or concomitant conditions or treatments that may cause immunosuppression may be at higher risk for infection and complications.[101]

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