Dr Toni Hazell discusses the identification and diagnosis of patients with monkeypox, providing practical advice on case management and infection control in primary care

Image of Dr Toni Hazell

Dr Toni Hazell

Read this article to learn more about:

  • the symptoms, epidemiology, and differential diagnoses of monkeypox
  • the definitions of possible and confirmed cases, and what actions to take
  • the role of primary care in reporting and referring patients with the disease.

Key points

Implementation actions for STPs and ICSs

Read this article online at: GinP.co.uk/457021.article

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There is a new infectious disease around. The first cases were identified in people who had returned to the UK from abroad (Nigeria), but soon it became apparent that the disease is spreading within the UK.1 Cases are rising on a seemingly exponential basis. Sound familiar? There is a distinct whiff of 2020 in the air, as everyone keeps their fingers crossed that monkeypox is not going to be the next COVID-19. As of 26 June 2022, there have been 1076 cases in the UK.1 Although monkeypox is now a notifiable disease in England,2 it is not just the UK that is affected—since May 2022, monkeypox has been reported in many countries in which it is not usually endemic, and public health investigations have not always found a clear travel link, suggesting that there is significant community transmission.3 It is thought that one of the factors behind the current outbreak is the cessation of smallpox vaccination programmes: a clear warning for us all in these times of increasing anti-vaccination messages.4

Work is ongoing to rename monkeypox amid concerns that the name is stigmatising and discriminatory—we saw similar actions taken when the variants of COVID-19 were renamed with Greek letters instead of being named after the place in which they were first identified. At the time of writing, however, the disease is still known as monkeypox.5

Monkeypox is a viral zoonosis. It was first recorded in monkeys in a Danish laboratory in 1958, then in humans in the Democratic Republic of the Congo in 1970.6 Since smallpox was eradicated, the disease has become the main source of human outbreaks of orthopox viruses in Africa.7 Thankfully, it is much less serious than smallpox, with most people experiencing a mild, self-limiting illness and recovering within 3 weeks, although some people can become more seriously ill.7

How does monkeypox present?

The key symptoms of monkeypox are shown in Figure 1. Initially, the disease manifests in a similar way to other acute viral illnesses, with a fever and/or chills, lymphadenopathy, headache, myalgia, backache, and fatigue.7 This first phase can last for up to 5 days, and is followed by a second phase characterised by the onset of a rash—the initial symptoms may lessen or resolve completely by the time the rash emerges.7 Most people have now seen photos of the distinctive pox lesions that tend to come at a later stage: no one is likely to miss a case that presents like this (see Figure 2).8 Unfortunately, the initial rash is not as distinctive—it can be maculopapular, and often starts on the face before spreading.7

Figure 1

Figure 1: The key symptoms of monkeypox

© Farosofa/stock.adobe.com

Figure 2: The evolution of monkeypox lesions

Figure 2: The evolution of monkeypox lesions8

Enter image captionDermal manifestations of monkeypox on a patient in Israel, 2018. Maculopapular rash was apparent on the face (A) and body on the day of hospital admission. A lesion on the left proximal extremity (B) was suspected to be a rickettsial eschar. After 3 days, the rash changed into vesicles and pustules on the face (C) and body (D). Skin resolution was apparent 13 days after admission; pustules and vesicles crusted and were shed (E, F). A timeline of disease progression (G) has been omitted from this version of the figure.

Erez N, Achdout H, Milrot E et al. Diagnosis of imported monkeypox, Israel, 2018. Emerg Infect Dis   2019; 25  (5): 980–983. Available at: wwwnc.cdc.gov/eid/article/25/5/19-0076_article

The preponderance of rash symptoms occurs on the palms of the hands and soles of the feet, but there may also be lesions on the genitalia, conjunctivae, corneas, and mucous membranes of the mouth.7 Typically, individual lesions are up to 1 cm in diameter—there may just be a few, but there can be several thousand.7 The eruptions evolve from a maculopapular rash to a vesicular rash, and then to the typical pustular presentation of a pox virus.7 Once the rash has evolved into pustules, it will generally crust and come off in flakes and scales over a period of 2–3 weeks.7

However, many of the current cases in England have an atypical presentation.9 Some patients have no documented prodrome and, in several patients, the rash began in the genital region instead of on the face, hands, and feet.9

Differential diagnoses

Primary care clinicians should always remember the basics of diagnosis: not every maculopapular rash with a fever will be monkeypox. Important differentials not to miss include HIV seroconversion (maculopapular rash with a fever and lymphadenopathy),10 and secondary syphilis (rash on the palms of the hands and soles of the feet and lymphadenopathy).11 Other conditions that may present with similar rashes include chickenpox, measles, smallpox, and scabies,12 and clinicians should be aware that malaria and typhoid are common causes of fever in people travelling from Africa to the UK.7

Transmission of monkeypox

One of the key problems with controlling COVID-19 is the fact that individuals are infectious before they have symptoms—this is often the case with other viruses, such as chickenpox, but it is thankfully not the case with monkeypox, for which there is no evidence of infectiousness before the onset of prodromal viral symptoms.3 For most patients, transmission will not be airborne, and will instead occur through close direct contact with patients or with fomites (contaminated household objects).3,7,12,13 This means that good hygiene, regular cleaning of surfaces and domestic equipment, and regular washing of clothes are key ways to reduce transmission.3 There is a lack of good evidence as to whether monkeypox is present in genital secretions,12,13 so all four UK public health agencies have advised, on a precautionary basis, that anyone with monkeypox should use condoms for 8 weeks after diagnosis, and abstain from sex while symptomatic.3

Current guidance states that proximity to monkeypox lesions is the greatest cause of transmission, and that patients with monkeypox should avoid close contact with other people until their lesions have healed and scabs dried off,3,7,12,13 meaning that patients are likely to remain infectious until this has happened.3,13

What is the role of primary care?

Identifying cases

This advice may evolve, but as of 6 July 2022, a probable case is defined by the UK Health Security Agency (UKHSA) as outlined in Box 1.14 Although anyone can be affected, most cases have been in men who have sex with men, so healthcare practitioners should have a higher index of suspicion in this group.1

Box 1: Definition of a probable case14

  • A person with an unexplained rash on any part of their body, plus one or more classical symptom or symptoms of monkeypox infection[A] since 15 March 2022 and who:
    • has an epidemiological link to a confirmed or probable case of monkeypox in the 21 days before symptom onset or
    • has reported a travel history to West or Central Africa in the 21 days before symptom onset or
    • is a gay, bisexual, or other man who has sex with men.

[A] For the purposes of this definition, ‘classical symptoms’ are an acute illness with a fever over 38.5°C, intense headaches, myalgia, arthralgia, back pain, and lymphadenopathy.

UK Health Security Agency. Monkeypox: case definitions. www.gov.uk/guidance/monkeypox-case-definitions

Contains public sector information licensed under the Open Government Licence v3.0.

The UKHSA has also produced definitions of possible and confirmed cases. A possible case is anyone with early febrile symptoms compatible with monkeypox infection who has had known contact with a confirmed case within 21 days of symptom onset, and should be treated in the same way as a probable case.9,14 A confirmed case relies upon laboratory confirmation via a positive polymerase chain reaction test, and their need for admission should be assessed based on either clinical or self-isolation requirements.9,14 It is no longer the case that patients with a positive test result need to be transferred to a designated centre for the care of high-consequence infectious disease.9,14

Many GPs are still doing full phone triage, including those like the author, for whom it was routine even before the pandemic. The latest figures show an increase in GP appointments conducted over the phone from 3.2 million in April 2019 to 7.8 million in April 2022, rising from 14.22% to 33.03% of all appointments held.15,16 Practitioners therefore need to be able to identify a probable case on the phone. For those practices that allow direct booking of face-to-face appointments, it may be sensible for receptionists to enquire about the presence of a rash and arrange phone triage for all rashes, which could include a photo being sent by text message.

Testing and referral

If there is concern that a patient has monkeypox, the case should first be discussed with the local infectious disease specialist.7,9 It may then be appropriate to escalate the case to the Imported Fever Service (IFS).7,9,17 If it is agreed that monkeypox is a possible diagnosis, the local health protection team (HPT)18 must be informed, and testing will be arranged by the IFS, which will advise on what samples should be obtained.7,9 The patient should be advised to self-isolate at home for 21 days, as should all high-risk contacts and those who have been risk-assessed and are well.1,3 The only exceptions to this are when leaving the house for testing or on the instructions of the specialist team, when private transport should be used if possible, lesions should be covered (for example, with bandages), and a face covering must be worn.3 Patients can be reassured that testing and treatment for monkeypox are free on the NHS, no matter what their nationality, residency, or immigration status.7 If the patient does not require admission for clinical reasons, and self-isolation at home is not possible for social or medical reasons following clinician assessment, they should isolate in a single room at negative or neutral pressure at a local hospital site, with respiratory protective equipment and personal protective equipment (PPE), pending test results.9,14

Case management and infection control

Management is largely symptomatic, although some patients with complications may need to be admitted to hospital. Complications can include pneumonia, sepsis, encephalitis, and loss of vision due to corneal infection.12 There is still uncertainty about whether the risk of complications is increased in children, pregnant women, and those who are immunocompromised.3

There is also a dearth of accurate data on the risk of death—the best information currently available is that, in a 2017 outbreak in Nigeria, there was a 3% case fatality rate, although the case fatality rate of monkeypox has historically ranged from 0–11%.12 The West African clade—the only one detected in Europe so far—has a historical fatality rate of 3.6% according to recent studies.9 However, this current outbreak is atypical in that it is happening in several nonendemic countries, and many patients have no direct travel link to an endemic area.

If a patient arrives at the surgery without calling ahead and there is a suspicion of monkeypox, then healthcare professionals should be aware of the risk of transmission through fomites and should avoid touching the patient’s skin or clothing with bare hands. Guidance that predates this current outbreak recommends that healthcare professionals should wear gloves and observe strict hand hygiene,7 but recent Government guidance recommends increased use of PPE, as outlined in Box 2.3 The room that the patient was assessed in should not be used after transfer;7 the practice should contact their local HPT18 for advice about cleaning and decontamination of the room.7 Healthcare professionals who are pregnant or immunocompromised should not be involved in the care of these patients.3

The referral procedures mentioned in the section Testing and referral  should be followed. Decisions to be made in secondary care may include whether to use the antiviral medication tecovirimat; at the time of writing, this medication has EU approval,19,20 but has not been approved by the Medicines and Healthcare products Regulatory Agency, meaning that its use in the UK is off licence.9

Box 2: Minimum PPE for possible and probable cases3

  • Gloves
  • FRSM[A]
  • Apron
  • Eye protection if there is a risk of splash to the face and eyes (for example, when taking diagnostic tests).

[A] An FRSM should be replaced with an FFP3 respirator and eye protection if the patient presents with a lower respiratory tract infection with a cough and/or changes on their chest X-ray, indicating lower respiratory tract infection

PPE=personal protective equipment; FRSM=fluid-repellent surgical facemask; FFP3=filtering facepiece 3

If a patient with suspected or confirmed monkeypox presents in primary care, it is important to follow public health advice on contact management.1,3,9,21 All possible contacts will need to be risk-assessed according to monkeypox contact-tracing guidance,21 and only those in the highest exposure risk category will be advised to self-isolate for 21 days.1,3 This group consists of:21

  • people who have had direct exposure of broken skin or mucous membranes to a confirmed, symptomatic monkeypox case, their body fluids, or potentially infectious material without wearing appropriate PPE
  • people who have a penetrating sharps injury (including cleaning or laboratory staff) related to a monkeypox case.

Medium-risk contacts do not need to self-isolate, but should avoid close contact with children, pregnant women, and those who are immunocompromised.3,21 Clearly, this will have to be thought through, and some changes to work patterns will have to be made if the contact is a GP or other healthcare professional working in primary care.

In some cases, UK public health agencies may offer a post-exposure smallpox vaccination to high- and medium-risk contacts—the complete vaccination course is two doses given at least 28 days apart.9,21–24 The Joint Committee on Vaccination and Immunisation has proposed that vaccination should be offered in particular to men who have sex with men at highest risk of exposure, because of the large number of contacts in this group.23,24 The vaccine may also be offered to healthcare workers who are likely to be caring for patients with monkeypox, and to some staff working in sexual health services who have assessed suspected cases.22–25 More information and guidance on monkeypox vaccination can be found in the UKHSA’s dedicated guidance.22–24

Conclusion

The last 2 years have made people much more aware of the dangers of viral infections. The principles that everyone has learnt during the COVID-19 pandemic regarding good hand hygiene and cleanliness will go some way to reducing the spread of monkeypox. Early articles on COVID-19, with their case numbers in the tens and hundreds, now seem very outdated. Let us hope that this instance is different, and that we are reaching the peak of monkeypox cases rather than facing the start of another escalating situation.

Key points

  • Most patients with monkeypox have a mild, self-limiting illness and recover within 3 weeks
  • Serious complications can include pneumonia, sepsis, encephalitis, and loss of vision due to corneal infection
  • Human-to-human transmission primarily occurs through close physical contact, prolonged face-to-face contact, and contact with fomites
  • Patients are likely to remain infectious until lesions heal and scabs dry out
  • Possible and probable cases should be risk assessed and managed with help from local infectious disease specialists and the IFS
  • Identification through phone triage is key for infection control
  • Where interactions with potential monkeypox cases are necessary, the correct PPE needs to be worn
  • Medium- and high-risk contacts, including healthcare professionals, will be offered post-exposure prophylaxis in the form of the smallpox vaccine.

IFS=Imported Fever Service; PPE=personal protective equipment

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved in implementing new guidance at a system level. Our aim is to help you to consider how to deliver improvements to healthcare within the available resources.

  • Convene a multiprofessional team—including NHS, public health, and HPU staff—to define a local health plan for the diagnosis and management of monkeypox
  • Publish guidance to all healthcare providers, promoting the early recognition of possible cases
  • Ensure there is a robust, responsive, and accessible service to which healthcare professionals can refer suspected cases for further testing, contact tracing, and advice on isolation
  • Establish local infection control procedures to allow examination of suspected cases in dedicated areas and avoid the risk of transmission to others in healthcare facilities
  • Consider local public information campaigns to alert the population to the symptoms of monkeypox, and explain to them how to contact healthcare providers safely for further assessment
  • Review current electronic decision-support and triage systems to ensure that they have been updated to include monkeypox in their clinical algorithms.

STP=sustainability and transformation partnership; ICS=integrated care system; HPU=Health Protection Unit

Dr Toni Hazell

Portfolio GP, Tottenham, London

Note: At the time of publication (July 2022), some of the drugs discussed in this article did not have UK marketing authorisation for the indications discussed. Prescribers should refer to the individual summaries of product characteristics for further information and recommendations regarding the use of pharmacological therapies. For off-licence use of medicines, the prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Good practice in prescribing and managing medicines and devices for further information.

References

  1. UK Health Security Agency website. Monkeypox cases confirmed in England—latest updates. www.gov.uk/government/news/monkeypox-cases-confirmed-in-england-latest-updates (accessed 1 July 2022).
  2. BBC News website. Law makes monkeypox a notifiable disease in England. www.bbc.co.uk/news/health-61723964 (accessed 28 June 2022).
  3. UK Health Security Agency, Public Health Scotland, Public Health Wales, Public Health Agency Northern Ireland. Principles for monkeypox control in the UK: 4 nations consensus statement. UKHSA, May 2022. Available at: www.gov.uk/government/publications/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement/principles-for-monkeypox-control-in-the-uk-4-nations-consensus-statement
  4. Kraemer M, Tegally H, Piggot D et al. Tracking the 2022 monkeypox outbreak with epidemiological data in real-time. Lancet 2022; 22 (7): 941–942.
  5. Roberts M. Monkeypox to get a new name, says WHO. www.bbc.co.uk/news/health-61804132 (accessed 28 June 2022).
  6. Centers for Disease Control and Prevention website. Monkeypox. www.cdc.gov/poxvirus/monkeypox/index.html (accessed 22 June 2022).
  7. Public Health England. Monkeypox: information for primary care. London: PHE, 2019. Available at: assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/850059/Monkeypox_information_for_primary_care.pdf
  8. Erez N, Achdout H, Milrot E et al. Diagnosis of imported monkeypox, Israel, 2018. Emerg Infect Dis  2019; 25 (5): 980–983.
  9. Smith G. Monkeypox (MPX) cases in the UK—investigation and assessment of individuals suspected to have MPX and management of confirmed cases of MPX. Letter from the Chief Medical Officer, Scotland, 20 May 2022. Available at: www.sehd.scot.nhs.uk/cmo/CMO(2022)22.pdf
  10. NICE. HIV diagnosis in people with symptoms. NICE Clinical Knowledge Summary. Available at: cks.nice.org.uk/topics/hiv-infection-aids/diagnosis/symptomatic-hiv-infection/  (accessed 28 June 2022).
  11. NICE. When should I suspect syphilis? NICE Clinical Knowledge Summary. Available at: cks.nice.org.uk/topics/syphilis/diagnosis/when-to-suspect-syphilis/  (accessed 28 June 2022).
  12. World Health Organization website. Monkeypox. www.who.int/news-room/fact-sheets/detail/monkeypox (accessed 22 June 2022).
  13. Centers for Disease Control and Prevention website. Monkeypox: how it spreads. www.cdc.gov/poxvirus/monkeypox/transmission.html (accessed 22 June 2022).
  14. UK Health Security Agency website. Monkeypox: case definitions. www.gov.uk/guidance/monkeypox-case-definitions (accessed 22 June 2022).
  15. NHS Digital. Appointments in general practice, April 2022. Leeds: NHS Digital, May 2022. Available at: digital.nhs.uk/data-and-information/publications/statistical/appointments-in-general-practice/april-2022
  16. NHS Digital. Appointments in general practice, April 2019. Leeds: NHS Digital, May 2019. Available at: digital.nhs.uk/data-and-information/publications/statistical/appointments-in-general-practice/april-2019
  17. Public Health England website. Imported fever service (IFS). www.gov.uk/guidance/imported-fever-service-ifs (accessed 22 June 2022).
  18. GOV.UK website. Find your local health protection team in England. www.gov.uk/health-protection-team (accessed 22 June 2022).
  19. Specialist Pharmacy Service website. Tecovirimat. www.sps.nhs.uk/medicines/tecovirimat/ (accessed 22 June 2022).
  20. European Medicines Agency website. Tecovirimat SIGA. www.ema.europa.eu/en/medicines/human/EPAR/tecovirimat-siga (accessed 22 June 2022).
  21. UK Health Security Agency. Monkeypox contact tracing guidance: classification of contacts and advice for vaccination and follow up. London: UKHSA, 2022. Available at: www.gov.uk/government/publications/monkeypox-contact-tracing
  22. UK Health Security Agency. Recommendations for the use of pre and post exposure vaccination during a monkeypox incident. London: UKHSA, 2022. Available at: www.gov.uk/government/publications/monkeypox-vaccination
  23. UK Health Security Agency. Smallpox and monkeypox: the green book, chapter 29. London: UKHSA, 2022. Available at: www.gov.uk/government/publications/smallpox-and-vaccinia-the-green-book-chapter-29#full-publication-update-history
  24. UK Health Security Agency website. Monkeypox outbreak: vaccination strategy. www.gov.uk/guidance/monkeypox-outbreak-vaccination-strategy (accessed 22 June 2022).
  25. Mahase E. Monkeypox: healthcare workers will be offered smallpox vaccine as UK buys 20,000 doses. BMJ 2022; 377: o1379.

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