Pan American Health Organization · Provisional technical note, June 2022
Provisional technical note to support clinical diagnosis and differential diagnosis of monkeypox for health professionals in primary care and emergency services.
- Issuer
- Pan American Health Organization
- Edition
- Provisional technical note, June 2022
- Audience
- Health professionals, especially in primary health care services, sexually transmitted infection clinics, specialized units providing care for people living with HIV, and emergency services
- Evidence
- Expert consensus based on early outbreak reports
- Reviewed
- 18 Oct 2026 · GMJ
What this guideline says
GMJ summary
This provisional technical note from the Pan American Health Organization provides practical guidance for health professionals to recognise, diagnose and differentiate monkeypox from other conditions during the 2022 multi-country outbreak. The document addresses the atypical presentation of cases in non-endemic regions, where the majority of affected persons are men who have sex with men, with initial symptoms often presenting as anogenital rash rather than the classic systemic onset.
The guidance emphasises that monkeypox is a self-limiting viral infection characterised by fever, adenopathies and an evolving rash (macules to papules, vesicles, pustules and crusts over 3 to 7 days), with an incubation period of 7 to 14 days (range 5 to 21 days). Transmission occurs through close contact with lesions, respiratory secretions, bodily fluids and contaminated objects. The document provides detailed photographic references for clinical diagnosis and differential diagnosis from herpes simplex, syphilis, chickenpox, impetigo and hand-foot-and-mouth disease, noting that co-infections with sexually transmitted infections have been reported and should not rule out monkeypox.
Management is symptomatic and supportive, with appropriate wound care to prevent secondary bacterial infections and assessment for sexually transmitted co-infections. Infection prevention and control measures require contact and droplet precautions, with patients isolated until lesion crusts detach (7 to 14 days after onset).
Key points
For clinicians — doses and thresholds as stated in the guideline
- Incubation period: 7 to 14 days, with a range of 5 to 21 days
- Classic prodromal symptoms: fever, weakness, headache, sometimes cough and pharyngeal pain, and adenopathies
- Mucocutaneous lesions evolve from macules to papules, vesicles, pustules and crusts over 3 to 7 days; lesions remain infective until crust detachment at 7 to 14 days
- In the 2022 outbreak, initial presentation often includes oral lesions, anogenital lesions and adenopathies, with lesions at different stages observed simultaneously (atypical)
- Skin lesions typically appear 1 to 3 days after fever and adenopathies in classic presentation
- Isolation with contact and droplet precautions required for suspected cases in health facilities
- Treatment is symptomatic and supportive; assess for sexually transmitted co-infections, particularly syphilis
- Differential diagnosis includes herpes simplex, primary or secondary syphilis, chickenpox, impetigo and hand-foot-and-mouth disease; co-infection with other sexually transmitted infections does not rule out monkeypox
Differential Diagnosis of Monkeypox Lesions
Table extracted from the guideline
| Disease | Clinical Features |
|---|---|
| Herpes simplex | Very painful polycyclic lesions that evolve to crust, usually in people with a history of herpes |
| Primary syphilis | Firm, painless chancre with a clean base |
| Secondary syphilis | Roseola or disseminated papules that affect the palms and the soles of the feet |
| Chickenpox | Starts on the upper back as asynchronous papules that evolve into vesicles and scabs |
| Impetigo | Meliceric (yellowish) crusts, sometimes with blisters, caused by bacterial infection |
| Hand-mouth-foot disease | Common in childhood but can occur in adults; caused by enteroviruses; fever and lesions on mucosa, mouth, palms and buttocks |
Source: Pan American Health Organization, Guidance on Clinical Suspicion and Differential Diagnosis of Monkeypox. Reproduced in summary form.
From the guideline
Verbatim
“diagnosis of an infection such as syphilis or lymphogranuloma venereum should not rule out infection with the monkeypox virus”
Editor’s perspective
Why this matters for Georgia and the region
Prof. Giorgi Pkhakadze, MD, MPH, PhD
Editor-in-Chief, Georgian Medical Journal · Chair, Public Health Institute of Georgia · WHO consultant, health and migration
As we have seen with COVID-19, emerging infectious diseases do not respect borders, and Georgia's position as a regional transport hub makes clinical preparedness for monkeypox essential even in the absence of endemic transmission. This PAHO guidance is particularly valuable because it addresses the atypical presentations seen in the 2022 outbreak, which differ substantially from textbook descriptions—I would emphasise to Georgian clinicians the importance of maintaining high clinical suspicion for anogenital lesions in sexually active adults, particularly men who have sex with men, and the critical point that sexually transmitted co-infections do not exclude monkeypox. The main implementation challenge for Georgia will be ensuring that frontline providers in sexual health services, HIV clinics and emergency departments have access to rapid orthopoxvirus PCR diagnostic capacity, as clinical diagnosis alone is insufficient and our laboratory network would require technical support and quality assurance for this specialised testing.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 18 Oct 2026
Applicability
Georgia and the South Caucasus
For Georgia and the South Caucasus region, this guidance is relevant for strengthening surveillance and clinical recognition of monkeypox in the context of international travel and potential importation from affected regions. National programmes would need to consider adaptation of case definitions for local surveillance systems, training of primary care providers and sexual health clinic staff in recognition of atypical presentations, establishment of laboratory diagnostic capacity for orthopoxvirus PCR testing, and development of infection prevention and control protocols for healthcare facilities. Given Georgia’s position as a transit corridor and the presence of mobile populations, preparedness for identification and management of imported cases would be prudent, particularly in urban centres with international connectivity and within services providing care for key populations at higher risk during the 2022 outbreak.
Questions this guideline answers
Quick answers
What is the incubation period for monkeypox?
The incubation period is 7 to 14 days, although it can range from 5 to 21 days.
How is monkeypox transmitted?
Transmission occurs from person to person through close contact with lesions, respiratory secretions and bodily fluids from symptomatic people, and through objects that have had contact with crusts or bodily fluids.
When are monkeypox lesions no longer infectious?
Lesions are infective until the detachment of the crust, which happens at 7 to 14 days after onset. Patients should remain isolated with contact and droplet precautions until this time.
How does the 2022 outbreak presentation differ from classic monkeypox?
In this outbreak, many cases present with anogenital rash as the first manifestation without systematically spreading to other body parts, pustules may appear before constitutional symptoms like fever, and lesions at different stages of development are observed simultaneously, all atypical of the classic form.
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- Issuer
- Pan American Health Organization
- Type
- Procedures, manuals, guidelines
- Edition
- Provisional technical note, June 2022
- Status
- Current
- Published
- 2022-01-01
- Scope
- Clinical suspicion, differential diagnosis and initial management of monkeypox
- Audience
- Health professionals, especially in primary health care services, sexually transmitted infection clinics, specialized units providing care for people living with HIV, and emergency services
- Licence
- CC BY-NC-SA 3.0 IGO
- Evidence
- Expert consensus based on early outbreak reports
- Record history
- Created 18 Oct 2026 · updated 18 Oct 2026 · next check Apr 2027
Pan American Health Organization. Guidance on Clinical Suspicion and Differential Diagnosis of Monkeypox. Provisional technical note, June 2022. Washington, D.C.: PAHO; 2022. (PAHO/PHE/IMS/22-0011).GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.
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