Preventing monkeypox outbreaks: Focus on diagnosis, care, treatment, and vaccination

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TL;DR

This narrative review examines the 2022 global monkeypox (Mpox) outbreak, focusing on diagnosis, treatment, care, and vaccination strategies. The paper highlights that while Mpox is generally self-limiting, severe cases occur in immunocompromised individuals, pregnant women, and children, and that smallpox vaccines provide cross-protection. The authors emphasize the urgent need for more research on antiviral therapies (tecovirimat, brincidofovir) and next-generation vaccines to control the rapid spread of Mpox in non-endemic countries.

Full summary

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**Background:** Monkeypox (Mpox), caused by the Orthopoxvirus monkeypox virus (MPXV), was first identified in humans in 1970. After decades of sporadic outbreaks in Central and West Africa, a large global outbreak began in May 2022, with over 100 cases reported across more than 100 countries. The paper notes that the annual incidence rate in the Democratic Republic of the Congo rose from 0.63 per 10,000 to 5.53 per 10,000. Two main strains exist: the Central African strain (more severe) and the West African strain (milder, lower human-to-human transmission). The virus has a double-stranded DNA genome (197 KB) encoding ~190 proteins and infects a wide range of mammals and rodents.

**Methods:** This is a narrative review. The authors synthesized published literature on Mpox diagnosis, treatment, care, and vaccination. They reference multiple clinical trials (NCT05559099, NCT05534984, NCT05534165 for tecovirimat; NCT02977715, NCT05512949, NCT05562323 for vaccines) and epidemiological studies.

**Key Results:** - Diagnosis: Real-time PCR of skin lesion samples is the preferred diagnostic method. Saliva samples contained MPX DNA in all 12 patients tested in one study. Rectal swabs (11/12) and nasopharyngeal swabs (10/12) also showed high detection rates. Lymphadenopathy is a key clinical sign distinguishing Mpox from chickenpox. - Treatment: No antiviral has received final FDA approval for Mpox. Tecovirimat (oral capsule or IV) inhibits the p37 protein, preventing virion egress. Three ongoing phase 2/3 trials are evaluating tecovirimat (NCT05559099, 450 participants; NCT05534984, 530 participants; NCT05534165, 120 participants). Brincidofovir (oral, lipid-conjugated cidofovir) was approved for smallpox in the USA as of June 2021 and has shown efficacy against orthopoxviruses. Cidofovir has nephrotoxicity concerns. Vaccinia Immune Globulin Intravenous (VIGIV) is recommended for severe T-cell immunodeficiency but has no proven benefit for Mpox. - Care: Supportive care (fluid/electrolyte balance, nutrition, antipyretics, secondary infection management) is the mainstay. Orthopoxviruses remain infectious on inanimate surfaces for up to 42 days. Effective disinfectants include 70% ethanol (≤1 min), 0.2% peracetic acid (≤10 min), and sodium hypochlorite (0.25–2.5%; 1 min). Human-to-human transmission occurs via respiratory droplets, direct contact with skin lesions, fomites, and possibly sexual contact (virus detected in semen). - Vaccination: Smallpox vaccination provides cross-protection (up to 85% reduction in severe disease among exposed family members). However, 1 in 5 confirmed Mpox patients in a US outbreak had prior smallpox vaccination. Live attenuated vaccines (Dryvax, MVA/IMVAMUNE/JYNNEOS, LC16m8) are being studied. MVA is immunogenic for >2.5 years but requires cold chain storage; LC16m8 is freeze-dried and does not. DNA-based vaccines targeting immunogens L1R, A27L, A33R, and B5R have shown protection in nonhuman primates. Three vaccine trials are listed: IMVAMUNE (phase 3, 1600 participants, CDC), JYNNEOS (phase 2, 210 participants, NIAID), and MoVIHvax (cohort, 100 participants, including HIV-positive individuals).

**Clinical Implications:** The 2022 outbreak demonstrates that Mpox is no longer a rare zoonosis but a rapidly spreading global threat, particularly among men who have sex with men. Early diagnosis via PCR of skin lesions is critical for containment. While tecovirimat and brincidofovir offer promise, their efficacy in Mpox patients remains under investigation. Vaccination strategies must balance the risks of live attenuated vaccines in immunocompromised populations against the need for protection. The waning of smallpox vaccine-induced immunity in younger populations is a key driver of the current outbreak. The authors call for accelerated research into next-generation vaccines (DNA-based, subunit) and antiviral therapies to prepare for future outbreaks and potential bioterrorism.