Confusion between Mpox (formerly Monkeypox) and Chickenpox is common because both diseases involve a distinctive rash. Mpox is caused by the Monkeypox virus, while Chickenpox is caused by the Varicella-zoster virus (VZV). Having had Chickenpox does not protect against contracting Mpox because the viruses belong to entirely separate and unrelated families, resulting in a lack of cross-immunity.
The Critical Difference Between Viral Families
Prior Chickenpox infection offers no immunity to Mpox due to the vast genetic distance between the viruses. Chickenpox is caused by the Varicella-zoster virus, which belongs to the Herpesviridae family. This family consists of large DNA viruses known for their ability to remain latent in the body after the initial infection, potentially reactivating years later as Shingles.
Mpox is caused by the Monkeypox virus, classified under the Orthopoxvirus genus within the Poxviridae family. Orthopoxviruses are genetically distinct from Herpesviruses, meaning the antibodies the body creates to neutralize VZV do not recognize the Mpox virus. Immune memory cells developed after a Chickenpox infection are highly specific to the VZV structure and cannot effectively neutralize the structurally different Orthopoxvirus. This biological separation ensures susceptibility to Mpox regardless of Chickenpox history.
Key Symptom and Transmission Distinctions
While both infections cause a rash, the progression and accompanying symptoms offer important distinctions. Mpox infection often begins with flu-like prodromal symptoms, including fever, headache, muscle aches, and notably, swollen lymph nodes (lymphadenopathy). This lymph node swelling is a distinctive feature that is not typically observed with Chickenpox.
Mpox lesions are deep-seated, painful, and develop uniformly, meaning all lesions are at the same stage (e.g., all pustules) across the body. These firm lesions can take two to four weeks to fully resolve. Chickenpox lesions, conversely, are typically superficial, itchy, thin-walled blisters that appear in successive crops, resulting in lesions at various stages of healing simultaneously.
Transmission methods also vary significantly. Chickenpox is highly contagious, primarily spreading through airborne respiratory droplets and direct contact with blister fluid. Mpox is much less contagious, primarily spreading through close, often prolonged skin-to-skin contact, direct contact with the rash or body fluids, or respiratory secretions during extended face-to-face proximity.
The Smallpox Vaccine and Cross-Protection
Although Chickenpox does not confer immunity, a related vaccine provides protection against Mpox. The Smallpox vaccine uses the Vaccinia virus, which targets the Orthopoxvirus family—the same genus as the Mpox virus. This close genetic relationship means the immune response generated by the Smallpox vaccine is cross-protective.
Historical data from the 1980s suggested that the traditional Smallpox vaccine provided an estimated 85% cross-protection against Mpox infection. Today, newer-generation Smallpox vaccines like JYNNEOS are used for pre-exposure or post-exposure prophylaxis in people at high risk. Studies indicate this vaccine offers significant protection, highlighting the strong biological link between the Smallpox and Mpox viruses.