07/06/2026
WHAT DOCTORS MUST KNOW ABOUT MPOX
MPOX — Comprehensive Clinical Reference (June 2026)
1. THE VIRUS & CURRENT EPIDEMIOLOGICAL LANDSCAPE
Mpox (MPXV) comprises two primary clades: Clade I (subclades Ia/Ib), historically the ‘Congo Basin’ strain, endemic to Central Africa with higher virulence (case fatality rate 1–10%); and Clade II (subclades IIa/IIb), the ‘West African’ strain, less virulent (survival >99.9%). Clade IIb caused the 2022 global outbreak. 
The 2022 global outbreak was declared a WHO Public Health Emergency of International Concern, affecting 122 countries — 115 of which had never reported mpox cases — with over 87,000 cases. It significantly differed from prior outbreaks, with a large majority of cases among men who have s*x with men (MSM), and s*xual in*******se being the main route of transmission. 
In August 2024, WHO declared a second PHEIC due to the emergence of MPXV clade Ib in the DRC and spread to neighbouring African countries and sporadically beyond Africa. The WHO PHEIC was lifted in September 2025 as cases declined, but clade IIb continues to circulate globally at low levels. 
Key point for a travel medicine/international practice: You can see either clade depending on your patients’ travel history.
2. TRANSMISSION — HOW IT SPREADS
MPXV is usually transmitted from person to person through close, sustained physical contact. In the clade I outbreak, transmission has occurred through s*xual contact, day-to-day household contact, and in healthcare settings when PPE was not available. In the ongoing clade II outbreak, transmission has been almost exclusively associated with s*xual contact. 
In the DRC clade I outbreak, MPXV is primarily thought to spread through respiratory droplets via coughs, sneezes, or talking that facilitate virus transfer to nearby individuals. Previous outbreaks, particularly among children in West and Central Africa, have demonstrated this mode of transmission. 
Other routes include:
• Direct contact with lesion fluid, scabs, or contaminated materials (bedding, clothing)
• Zoonotic transmission from infected animals (rodents, primates)
• Needlestick injuries (documented in healthcare workers)
• Mother-to-child (vertical transmission possible)
3. CLINICAL PRESENTATION
Incubation Period
The incubation period is roughly 1–2 weeks, though clinicians are currently recommended to monitor patients up to 21 days. A person is not contagious during this period. 
Prodrome
People with mpox may develop an early set of symptoms (prodrome) including fever, malaise, headache, sore throat, or cough, and — in many cases — swollen lymph nodes. 
Lymphadenopathy is a distinguishing feature from smallpox and chickenpox.
The Rash — Four Progressive Stages
Within three days of experiencing initial symptoms, the rash can spread quickly and eventually turns into small fluid-filled sacs known as vesicles. The rash progresses through stages: macules → papules → vesicles → pustules → scabs/crusts. 
Lesions typically develop at the same time and evolve together on any given part of the body. For both clade I and clade II infection, lesions often occur in the ge***al and anorectal areas or in the mouth. 
Sores can occur on the mucosa — in the mouth, nose, throat, or digestive tract. 
The patient is contagious from onset of symptoms until all lesions have fully healed and scabs have fallen off.
Clade Differences in Severity
Clade I tends to cause more serious illness and is linked to more deaths. It may spread more easily than clade II. Clade II causes less severe disease and is less likely to cause death. 
4. COMPLICATIONS
Recognised complications include secondary bacterial infections, pneumonia, sepsis, encephalitis, and loss of vision with severe eye infection. 
Additional significant complications include:
• Proctitis — particularly painful, common in a**l transmission (clade II)
• Pharyngitis/tonsillitis — can cause difficulty swallowing
• Urethritis/balanitis
• Corneal ulceration — can cause permanent visual impairment
• Secondary bacterial superinfection of lesions (most common complication)
• Respiratory compromise — particularly clade I
High-Risk Groups for Severe Disease
• Immunocompromised patients (especially advanced HIV/AIDS)
• Pregnancy
• Children under 5 (clade I: CFR >10% in this group)
• Patients with eczema or atopic dermatitis (disseminated disease risk)
Long Mpox
A study published in the Annals of Internal Medicine assessed 154 people infected with clade IIb mpox 1–18 months after diagnosis and found scarring plus bowel, urinary, and s*xual problems more than a year after infection. While this focused on clade IIb, the findings offer valuable insights into the types of lasting physical and psychosocial effects the virus can cause. 
5. DIAGNOSIS
Consider mpox as the cause of a diffuse or localized rash, particularly if there is recent travel to an outbreak area. Evaluate any individual presenting with certain ulcers or rash for HIV and STIs simultaneously. Conduct a thorough patient history, including detailed travel and s*xual histories, to assess possible exposure. 
Gold standard testing: PCR for MPXV DNA from lesion swabs (roof of lesion, lesion base, or exudate). Throat/rectal swabs also useful.
Differential diagnosis: Chickenpox (varicella), syphilis (secondary), herpes simplex, molluscum contagiosum, hand-foot-mouth disease, scabies, bacterial skin infection.
6. PRECAUTIONS FOR YOU AS A PRACTITIONER
Personal Protective Equipment (PPE) — Non-Negotiable
Healthcare providers should practice effective hand hygiene and don personal protective equipment — gown, gloves, eyewear, and an N-95 or comparable respirator mask — before evaluating or collecting a specimen from a patient with suspected mpox. 
PPE required includes: gown, gloves, eye protection (goggles or face shield covering the front and sides of the face), and a NIOSH-approved particulate respirator with N-95 filters or higher. 
Sharps Safety — Critical
Because of the risk for sharps injuries, CDC advises against unroofing, opening, or aspirating mpox lesions with sharp instruments, and against recapping used needles. There have been documented mpox infections through needlestick injuries, including a nurse infected through a needlestick while sampling a lesion. 
Waste Management
Waste contaminated with clade I or clade II MPXV is designated as Category B infectious substance. Handle, store, treat, and dispose of soiled PPE, patient dressings, and clinical waste in accordance with hazardous materials regulations. 
Environmental Infection Control
Hand hygiene, dedicated personal items, appropriate handling of linens and laundry, cleaning and disinfection of the environment, and waste management should be followed for persons with mpox until all lesions are healed. 
Isolate Suspected Cases
Place patients with suspected mpox in a single-occupancy room with the door closed. If a dedicated room is unavailable, spatial separation and full PPE are essential.
Your Own Vaccination
As a healthcare worker with occupational exposure risk, JYNNEOS vaccination is indicated for you. Both ACAM2000 and JYNNEOS continue to be available for people at occupational risk for exposure.  JYNNEOS is preferred given its superior safety profile.
7. TREATMENT — EVIDENCE-BASED (2025 UPDATE)
Cornerstone: Supportive Care
Supportive measures for pain and other symptom control, as well as treatment of complications such as bacterial superinfection, are the mainstays of therapy. Fortunately, the prognosis in the context of clade IIb mpox is excellent, and the majority of affected individuals recover fully whether they receive medical attention or not. 
Pain management:
Many patients experience significant pain from skin lesions or mucosal involvement, including proctitis or pharyngitis. Pain can often be controlled with over-the-counter a**lgesics such as acetaminophen or NSAIDs. Some individuals may require gabapentin or opioid medications for severe pain. 
Antivirals — Updated Evidence
Tecovirimat (TPOXX):
Results from randomized placebo-controlled clinical trials have now demonstrated that tecovirimat is not effective as monotherapy for mpox. In the NIH-sponsored STOMP study, tecovirimat did not reduce time to clinical resolution, pain score, or rates of MPXV detection compared with placebo among participants with clade II mpox without advanced immunocompromise. The PALM007 trial found a similar lack of efficacy for clade I mpox in the DRC. Clinicians should not use tecovirimat as monotherapy for mpox. 
Use of tecovirimat as part of combination therapy with another antiviral agent can be considered for individuals with advanced immunocompromise, but should only be pursued in consultation with local/state health departments or the CDC. For combination use with brincidofovir, tecovirimat must be accessed via the CDC Expanded Access IND protocol. 
Brincidofovir / Cidofovir:
Brincidofovir is an oral prodrug of cidofovir and is FDA-approved for smallpox treatment. Cidofovir is available IV. Either can be added to tecovirimat in patients with or at high risk of severe mpox, typically given once weekly for 2 weeks. They should never be used concurrently with each other. 
IV cidofovir or oral brincidofovir can be used as adjunctive therapy in people with or at risk for severe disease, or in people who experience clinically significant progression while receiving tecovirimat, develop disease recrudescence, or are ineligible for tecovirimat. Brincidofovir is associated with less nephrotoxicity than cidofovir. 
Vaccinia Immune Globulin IV (VIGIV): Can be considered for severe or life-threatening disease in immunocompromised patients, in combination with antivirals.
Summary of current antiviral approach:
|Patient
Approach
MILD Supportive care only
MODERATE
| Consult CDC/ID; consider tecovirimat + brincidofovir ± VIGIV
Severe / immunocompromised |Consult CDC/ID; consider tecovirimat + brincidofovir ± VIGIV|
|HIV with low CD4 / advanced AIDS|Early antiviral combination + ART optimisation |
8. VACCINATION — PRE- AND POST-EXPOSURE
JYNNEOS (Imvanex/Imvamune): The preferred vaccine.
The standard regimen is two doses administered subcutaneously 28 days apart. Peak immunity is expected two weeks after the second dose. Estimated vaccine effectiveness for preventing mpox disease has ranged from 66–89% for the two-dose series. 
Post-Exposure Prophylaxis (PEP):
Postexposure prophylaxis using JYNNEOS is recommended within 4 days after exposure.  Vaccination within five to 14 days of exposure may reduce symptoms for those who go on to develop mpox illness. Close contacts of a confirmed case, particularly those who are immunocompromised, should receive two doses as PEP. 
Pre-exposure recommendations (for patients you counsel):
Pre-exposure vaccination is recommended for persons with occupational risk, those with planned travel to a country with a clade I mpox outbreak plus an additional risk factor (such as s*x with a new partner or attendance at large public events), and those with multiple s*xual partners, recent STI diagnosis, or s*x at commercial s*x venues where mpox is circulating. 
9. SPECIAL CONSIDERATIONS FOR YOUR INTERNATIONAL TOURIST PRACTICE
• Always take a travel history — ask specifically about recent travel to DRC, Central/Eastern Africa, or any current outbreak region
• Detailed s*xual history is essential — non-judgmental, routine inquiry
• Co-test for HIV and STIs in all mpox cases — co-infection is common and influences management
• HIV-positive patients with low CD4 counts are at very high risk of severe disease — low threshold for antiviral therapy consultation
• Consider clade I in travellers returning from Central Africa — more severe disease, broader transmission routes including respiratory droplets and household contact
• Notify public health authorities — mpox is a notifiable disease in most jurisdictions; reporting is mandatory
• Counsel patients on isolation — remain isolated until all lesions are fully crusted and healed
• Counsel on partner notification — s*xual and household contacts should be traced and offered PEP vaccination
10. YOUR PERSONAL PROTECTION CHECKLIST
• ✅ Ensure you are vaccinated with 2-dose JYNNEOS series
• ✅ Don full PPE (N-95, gown, gloves, eye protection) before any suspected mpox contact
• ✅ Never unroof or aspirate lesions with sharp instruments
• ✅ Triage suspected cases to isolated rooms promptly
• ✅ Know your local/national reporting pathway
• ✅ Know how to access tecovirimat combination therapy via expanded access if needed for severe/immunocompromised patients
• ✅ If you have a needlestick or unprotected exposure, seek PEP vaccination within 4 days and report to occupational health
Key reference sources: WHO Living Clinical Guideline (May 2025), CDC Clinical Overview (December 2025), NIH/NYSDOH Treatment Guidelines (July 2025), STOMP and PALM007 trial data (2025).
