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One Health Resource Center

Disclosures: Hoet is employed by Bavarian Nordic. Please see the study for all other authors’ relevant financial disclosures.
May 21, 2022
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Waning smallpox immunity ‘established the landscape’ for monkeypox resurgence

Disclosures: Hoet is employed by Bavarian Nordic. Please see the study for all other authors’ relevant financial disclosures.
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Waning population immunity against smallpox — a result of discontinued vaccination campaigns for the now-eradicated disease — “has established the landscape for the resurgence of monkeypox,” researchers said.

They came to that conclusion after systematically reviewing dozens of studies and other documents for data on the evolution of monkeypox epidemiology over the past 50 years, which revealed that cases have been increasing since routine smallpox vaccination ceased.

Monkeypox_Micro_CDC
A high percentage of monkeypox cases occur among people unvaccinated for smallpox. Source: CDC.

Their findings were published in February in PLoS Neglected Tropical Diseases, months before a growing number of monkeypox cases were reported in the United States and several other countries.

“Based on initial literature review, we thought there was an increase of number of cases of monkeypox, which was not systematically reported at that moment,” Bernard Hoet, MD, vice president of medical strategy at Bavarian Nordic, told Healio. “We thus thought it would be of use to document this formally.”

Bernard Hoet

Hoet and colleagues conducted a systematic review of 48 peer-reviewed studies and 18 gray literature sources, looking primarily at the number of cases of monkeypox, age at presentation, mortality and geographical spread.

Overall, the number of human monkeypox cases has been on the rise since the 1970s, they found, most dramatically in the Democratic Republic of the Congo (DRC). The median age at of patients with monkeypox increased from 4 years in the 1970s to 21 years between 2010 and 2019.

Overall, 8.7% of patients with monkeypox died — 10.6% (95% CI, 8.4%-13.3%) of those infected with the Central African clade of the virus and 3.6% (95% CI, 1.7%-6.8%) infected with the West African clade, which has been implicated in the recent cases.

The researchers noted that smallpox vaccination provides some cross-protection against monkeypox. A licensed vaccine that protects against monkeypox and smallpox — Bavarian Nordic’s Jynneos — was approved by the FDA in 2019 for adults aged 18 years or older in the U.S. The company said in 2020 that the U.S. had ordered millions of doses of the vaccine for the national stockpile.

According to Hoet and colleagues, 21 articles reviewed by the researchers reported smallpox vaccination status. Eleven of them described outbreaks from 10 different countries that included 49 patients with monkeypox — none of whom were vaccinated. In the other 10 articles, which reported data from outbreaks in the DRC and U.S., the proportion of monkeypox cases with a history of prior smallpox vaccination ranged from 4% to 21%. They noted that the highest percentage of vaccinated cases (21%) was found in the U.S. outbreak in 2003 that was linked to imported prairie dogs.

“Monkeypox is not a benign disease,” Hoet said. “This should be taken into account for the preparedness plans of authorities. We have a disease potential which seems to be materializing at the moment for which we have an option. It should raise the attention of health agencies to be prepared.”