What is the differential diagnosis and treatment approach for a patient presenting with rash, fever, and swollen lymph nodes, with a history of travel to endemic areas or contact with macaque monkeys, suspected of having either monkeypox or herpes B (Herpes simplex virus type B)?

Monkeypox vs Herpes B: Differential Diagnosis and Management

If you suspect either monkeypox or herpes B virus infection based on exposure history, immediately isolate the patient and initiate empiric antiviral therapy while awaiting confirmatory testing, as both infections carry significant morbidity and mortality risk.

Critical Distinguishing Features

Exposure History (Most Important Differentiator)

Monkeypox:

• Contact with infected prairie dogs, exotic animals, or humans with confirmed infection 1
• Travel to endemic areas in Africa (particularly Central and West Africa) 2, 3
• Recent sexual contact or close physical contact with infected individuals 2
• Exposure at child care centers or pet stores with infected animals 1

Herpes B:

• Definitive exposure: Bite, scratch, or mucous membrane contact with macaque monkeys (especially rhesus macaques) 1, 4
• Occupational exposure in laboratory personnel, veterinarians, or animal caretakers working with macaques 1, 4
• Contact with monkey saliva, tissues, or tissue fluids 4
• Possible (though rare) airborne transmission in clinical settings 4

Clinical Presentation Differences

Monkeypox:

• Prominent lymphadenopathy (swollen lymph nodes) - this is the key distinguishing feature from smallpox and other pox viruses 2, 3
• Fever, headache, fatigue, myalgia preceding rash by 1-3 days 2, 3
• Disseminated painful rash that may be predominantly anogenital in recent outbreaks 2
• Rash progresses through stages: macules → papules → vesicles → pustules → crusts 2, 3
• Incubation period: 5-21 days (typically 7-14 days) 5
• Usually self-limiting in immunocompetent hosts 2

Herpes B:

• Rapidly progressive fatal meningoencephalitis - this is the defining feature 1, 4
• Mild or absent oral lesions at bite/scratch site initially 1
• Vesicular lesions may appear at exposure site 4
• Neurological symptoms develop rapidly: altered mental status, ascending paralysis, encephalitis 4
• High mortality rate (approaching 70-80% if untreated) 4
• Incubation period: typically 2 days to 5 weeks 4

Diagnostic Algorithm

Immediate Actions (Within Hours)

1. Isolate patient immediately - both infections require source isolation with gloves, gown, and mask 1
2. Document exact exposure details:
   • Specific animal species involved 1
   • Date and nature of contact (bite, scratch, mucous membrane exposure) 1, 4
   • Geographic location and travel dates 1

Laboratory Testing

For Monkeypox:

• PCR testing of lesion material (swabs of exudate or crusts) is confirmatory 5
• Real-time or conventional PCR for orthopoxvirus, followed by monkeypox-specific PCR 5
• Genetic sequencing to identify clade (Clade IIb responsible for 2022 outbreak) 2
• Warning to laboratory: Notify lab of suspected monkeypox to ensure proper biosafety handling 1

For Herpes B:

• Serological testing is difficult and unreliable for acute diagnosis 1, 6
• PCR of vesicular fluid or CSF if neurological symptoms present 6
• High herpes B prevalence in macaques makes monkey testing challenging 1
• Cross-reactivity with HSV complicates serological diagnosis 6

Supporting Laboratory Tests

Monkeypox:

• CBC typically shows normal or mildly elevated WBC 5
• No specific laboratory abnormalities required for diagnosis 5

Herpes B:

• CSF analysis if neurological symptoms present (pleocytosis, elevated protein) 4
• MRI brain may show encephalitic changes 4

Treatment Approach

Monkeypox Treatment

Mild to Moderate Disease:

• Supportive care with symptom management 2, 3
• Isolation until all lesions have crusted and separated 2

Severe Disease or High-Risk Patients (Immunocompromised, Pregnant):

• Tecovirimat (TPOXX) 600 mg PO twice daily for 14 days (if ≥40 kg body weight) 7, 2
• Brincidofovir as alternative antiviral 2
• No cross-resistance between tecovirimat and brincidofovir 7

Herpes B Treatment

ANY suspected exposure requires immediate aggressive treatment:

• Immediate wound cleansing for 15 minutes with soap/water or povidone-iodine 4
• Start empiric antiviral therapy immediately - do not wait for confirmatory testing 4
• Acyclovir 800 mg PO 5 times daily OR valacyclovir 1000 mg PO 3 times daily 4
• Continue for minimum 14 days, longer if neurological symptoms develop 4
• If neurological symptoms present: IV acyclovir 10-15 mg/kg every 8 hours 4

Post-Exposure Prophylaxis

Monkeypox:

• JYNNEOS vaccine (modified vaccinia Ankara) preferred for post-exposure prophylaxis 2
• Administer within 4 days of exposure for optimal prevention, up to 14 days for disease attenuation 2
• ACAM2000 vaccine alternative but has more adverse effects 2

Herpes B:

• Prophylactic antiviral therapy for ALL macaque exposures involving bites, scratches, or mucous membrane contact 4
• Valacyclovir 1000 mg PO 3 times daily for 14 days 4

Critical Pitfalls to Avoid

1. Never dismiss the absence of recalled tick or animal bite - patients often do not remember or recognize exposure 1
2. Never delay treatment waiting for laboratory confirmation - both infections require immediate empiric therapy 8, 4
3. Never assume monkeypox is the diagnosis without considering herpes B in anyone with macaque exposure - herpes B has much higher mortality 1, 4
4. Never fail to warn laboratory personnel - both are biosafety hazards requiring special handling 1
5. Never use fluoroquinolones alone for suspected herpes B - they are ineffective against herpesvirus 4

Notification Requirements

Both infections are notifiable diseases requiring immediate reporting to local health protection units 1:

• Monkeypox: statutory notification required 1
• Herpes B: report as viral encephalitis 1