National Center for Emerging and Zoonotic Infectious Diseases

Updates from the 2022–2023 U.S. Mpox Outbreak: 

Epidemiology, Vaccine Safety, and Vaccine 

Effectiveness

ACIP Meeting

June 23, 2023

Faisal Syed Minhaj, PharmD, MPH, DABAT

Epidemic Intelligence Service Officer

Poxvirus and Rabies Branch
United States Mpox Case Counts April 2022–June 2023

https://www.cdc.gov/poxvirus/mpox/response/2022/mpx-trends.html
United States Mpox Case Counts January 1–June 6, 2023

Uptick in 

cases in 

Chicago

https://www.cdc.gov/poxvirus/mpox/response/2022/mpx-trends.html
Mpox cases reported to CDC by age and gender May 

2022–June 14, 2023

https://www.cdc.gov/poxvirus/mpox/response/2022/demographics.html

Data were available for 98.9% of cases 

reported to CDC
Mpox cases reported to CDC by race and ethnicity May 

2022–June 14, 2023

56 1050 8859 11782 5289 1894 753 340 196 64 71 42 81 10 Count within columns

https://www.cdc.gov/poxvirus/mpox/response/2022/demographics.html

Subject to reporting 

irregularities

Data were available for 93.7% 

of cases reported to CDC
Chicago Mpox Cases

Increases in mpox 

cases detected 

https://www.chicago.gov/city/en/sites/monkeypox/home/data.html
Cluster of cases in Chicago

▪ From March 18–June 12, Chicago identified 40 laboratory confirmed mpox 

cases

– All males with a median age of 36 years (IQR 23–49)

– 22 (55%) were vaccinated with 2 doses of JYNNEOS or 1-dose of ACAM2000

– 5 (13%) were partially vaccinated (i.e., 1 dose JYNNEOS)

– 13 (33%) were unvaccinated

▪ 11 were living with HIV

– 10 were vaccinated with 2 doses of JYNNEOS or 1 dose of ACAM2000 had 

well controlled HIV

▪ Median time from 2nd dose of JYNNEOS to mpox diagnosis was 8.4 months (IQR 

7.9–8.8 months)

https://www.cdc.gov/mmwr/volumes/72/wr/mm7225a6.htm
Cluster of cases in Chicago

▪ Individuals with 2 doses of JYNNEOS or 1 dose of ACAM2000 had self-limiting 

illness

– Lower prevalence of mucosal lesions

– None were hospitalized

▪ Individuals with 2 doses of JYNNEOS or 1 dose of ACAM2000 had a higher 

number of sexual partners 3 weeks before symptom onset compared to 

partially or unvaccinated

▪ Preliminary sequencing indicates the virus is the same B.1 variant of Clade IIB 

which is the predominant variant of the 2022–2023 outbreak

– There were no mutations that would confer increased pathogenicity

▪ This investigation is ongoing, however no similar clusters are being seen 

elsewhere in the U.S.

https://www.cdc.gov/mmwr/volumes/72/wr/mm7225a6.htm
Epidemiology of Mpox in Less Affected 

Populations
Mpox in Pregnant People in the U.S. 

▪ From May 11, 2022–May 31, 2023, 27 cases of mpox reported to CDC 

occurred in pregnant people

▪ All exposure were through close contact with a person with confirmed 

infection (including sexual or household contact)

▪ Infections occurred in all trimesters of pregnancy

▪ 11 (40.7%) received tecovirimat without adverse events reported

▪ Outcomes

– 3 (11.1%) pregnancy losses at <20 weeks 

– 6 (22.2%) live births

– 18 (66.7%) pregnancies ongoing
Neonatal Transmission and Breastfeeding 

Considerations

▪ Of 6 live births, two neonates developed lesions within one week after 

their mothers became symptomatic.

– Both neonates received oral tecovirimat; one received VIGIV.

– Both neonates responded to treatment and were discharged home.

– One breastfeeding neonate developed face and chest lesions 6 days 

after the mother developed breast lesions.

▪ One woman with isolated ocular lesions continued to breastfeed her 2-

year-old infant without transmission

– Breastmilk tested on two separate occasions was MPXV PCR negative

VIGIV: vaccinia immune globulin intravenous
Mpox in a U.S. Neonate

▪ 12 hours after vaginal delivery, it was learned 

that dad had active mpox and had contact with 

mom prior to delivery

▪ Mom developed lesions 1 day after delivery on 

the abdomen and tested positive for mpox

▪ Baby was given VIGIV as post-exposure 

prophylaxis

▪ At 4 days old, baby developed scalp lesions and 

tested negative for HSV, positive for mpox

▪ Baby was given tecovirimat and discharged at 17 

days old

▪ Full resolution 4 weeks after discharge

Scalp 

lesion, 

4 days old

Scalp 

lesion, 

13 days 

old

Nowalk A, Dunmore E (unpublished) VIGIV: vaccinia immune globulin intravenous
Mpox in a neonate in the United Kingdom

• Nine days before birth, dad developed a 

febrile illness, followed by a rash that 

resolved prior to the baby’s birth

• Four days after birth, a similar rash 

appeared on mom

• Nine days after birth, the infant also 

developed a similar rash and diagnosed 

with both mpox and adenovirus 

• Treated with 14 days of enteral 

tecovirimat and intravenous cidofovir

• Critically ill, requiring 4 weeks in ICU and 

14 days on mechanical ventilation before 

discharged home

Ramnarayan P, Mitting R, N Engl J Med. 2022 Oct 27;387(17):1618-1620. 
Epidemiologic Characteristics of Pediatric Cases in the 

U.S., May 17–September 24, 2022

Characteristic

% by age group, yrs

0–4 5–12 13–17

(n = 16) (n = 12) (n = 55)

Sex

Male 75% 50% 89%

Female 25% 50% 11%

Race or ethnicity

Black, non-Hispanic 44% 42% 49%

Hispanic or Latino 31% 42% 34%

White, non-Hispanic 19% 17% 9%

Asian, non-Hispanic — — 4%

American Indian or Alaska Native, non-Hispanic — — 2%

Native Hawaiian or other Pacific Islander, non-Hispanic 6% — —

Other, non-Hispanic — — 2%

Exposure setting and route

Sexual contact — — 97%

Household contact 93% 100% —

Other 7% — 3%

• <1% of U.S. cases among persons <18 years of age

• Among adolescents, cases predominantly after male-to-male sexual 

contact

• Among younger children, predominantly household contact

Hennessee I. MMWR Morb Mortal Wkly Rep 2022;71:1407–1411. 
MPXV Infections Among 

Children Aged ≤12 Years —

U.S., September 25–

December 31, 2022

▪ Mpox cases in children ≤12 

years are rare

▪ Transmission to children is 

primarily from mpox positive 

caregiver interactions

Nemechek K, MMWR Morb Mortal Wkly Rep 2023;72:633–635.
Healthcare Personnel (HCP) Infections Reported to 

CDC

▪ During investigation of cases where HCP was noted within a case report 

form, the exposure was often outside the workplace

▪ After excluding all other more likely exposures, only 23 (0.08%) cases 

potentially involved HCP exposed at work

▪ HCP infections are very rare
Healthcare Personnel Cases That Consulted CDC (n=6)

▪ Three were sharps injuries while trying to aspirate/unroof lesions

– CDC has since revised its recommendations to discourage unroofing 

lesions

– Globally, this constitutes the majority of HCP infections

▪ Two cases among HCP where improper personal protective equipment was 

worn

▪ One case where the exposure route was unclear
Vaccine: Coverage, Safety and Effectiveness
First and Second Doses of JYNNEOS Vaccine 

Administrations−United States, May, 2022 to May 2023

Overall vaccine coverage

1-dose: 36.7% and 2-dose: 22.7%
Risk for recurrent mpox outbreak lasting >3 months, 

by immunity level — United States, 2023

Pollock ED. MMWR Morb Mortal Wkly Rep 2023;72:568–573.
Cumulative Monkeypox virus infections relative to 

2022, by immunity level — United States, 2023

Pollock ED. MMWR Morb Mortal Wkly Rep 2023;72:568–573.
Cumulative Monkeypox virus infections relative to 

2022, by immunity level — United States, 2023

Pollock ED. MMWR Morb Mortal Wkly Rep 2023;72:568–573.

>50% is needed 

to significantly 

decrease the risk 

of large outbreaks 
JYNNEOS Vaccine Safety Monitoring 

▪ CDC vaccine safety monitoring is ongoing using two surveillance systems:

– Vaccine Adverse Event Reporting System (VAERS)

– Vaccine Safety Datalink (VSD)

▪ V-safe data collection for mpox vaccines was available from November 

2022 through March 21, 2023
JYNNEOS Vaccine Safety Findings Summary

▪ The adverse events most commonly reported to VAERS have been injection 

site symptoms (redness, swelling, pain, itching)

▪ Uncommon, but expected, adverse events that have been reported to 

VAERS include:

– Syncope: 49 reports per million doses administered

– Anaphylaxis: 2 reports per million doses administered

▪ Myocarditis and pericarditis are adverse events of special interest

– Observed rates are consistent with expected background rates
JYNNEOS Vaccine Safety Conclusions

▪ VAERS and VSD data do not suggest an increased risk for myocarditis or 

pericarditis following JYNNEOS, but the possibility of a small risk cannot be 

excluded

▪ The frequencies of local and systemic reactions reported to v-safe after 

mpox vaccine were similar to those reported in clinical trials

▪ No new or unexpected safety concerns have been identified
Epic Cosmos Study: Methods

▪ Data Source: Epic’s electronic health record (EHR) platform, Cosmos, which includes 

records from >173 million patients across the U.S.

▪ Design: Case-control analysis, matched 1:4 based on week of index event, HHS region, 

and gender identity

– Cases: Patients with an mpox diagnosis or positive orthopoxvirus or MPXV laboratory 

result from 8/15 - 11/19/2022

– Controls: Patients with an incident HIV diagnosis or HIV pre-exposure prophylaxis 

(PrEP) prescription from 8/15 - 11/19/2022

▪ Analysis:

– Vaccine effectiveness (VE) estimated using conditional logistic regression

– Adjusted for age, race/ethnicity, social vulnerability index, immunocompromising 

conditions

– Stratified by route of administration and immunocompromised status
Epic Cosmos Case-Control Study: VE for 1-Dose and 2-

Dose JYNNEOS vaccination

https://www.nejm.org/doi/full/10.1056/NEJMoa2215201?query=featured_home

*Adjusted for age, race/ethnicity, social vulnerability index, and immunocompromising conditions.

Cases/controls matched on week of index event, HHS region, gender identity.
Multi-jurisdictional Case-Control Study: Methods

▪ Design: Case-control study

▪ Population: Men who have sex with men; ages 18-49; 12 U.S. jurisdictions

▪ Methods:

– Cases identified from jurisdictions’ probable and confirmed mpox case 

lists

– Controls identified from healthcare settings providing HIV PrEP or 

sexually transmitted infection (STI) clinics

– Demographics, exposure history, and vaccination history collected using 

electronic surveys

– Vaccination status confirmed by state immunization registries

– Analysis: 

– VE estimated using conditional logistic regression

– Adjusted for age, race/ethnicity, immunocompromising conditions

– Stratified by route of administration and immunocompromised status
Multi-jurisdictional Case-Control Study Results: VE for 

1-Dose and 2-Dose JYNNEOS vaccination

https://www.cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w
Multi-jurisdictional Case-Control Study Results: VE for 

1-Dose and 2-Dose JYNNEOS vaccination

https://www.cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w
New York State Case-Control Study: Methods

▪ Design: Case-control study

▪ Data source: Linkage of case surveillance to immunization registry in New York 

State, excluding New York City

▪ Population: males at birth aged ≥18 years

▪ Methods:

▪ Cases: Adult male mpox cases during July 24 – October 31, 2022

▪ Controls: Adult male STI cases (rectal gonorrhea or primary syphilis) during July 

24 – October 31, 2022

▪ Vaccination status obtained from immunization registries

▪ Analysis: Conditional logistic regression model adjusted for week of diagnosis, 

race, age, region within state
New York State Case-Control Study Results: VE for 1-

Dose and 2-Dose JYNNEOS vaccination

*Adjusted for age, race/ethnicity, week of diagnosis, and geographic region

https://www.cdc.gov/mmwr/volumes/72/wr/mm7220a4.htm
VE against mpox ranges from 36%–75% for 1-Dose and

66%–89% for 2-Dose JYNNEOS vaccination
Vaccine effectiveness of JYNNEOS against mpox

▪ JYNNEOS vaccine is effective at reducing risk of mpox disease

▪ Protection provided by both 1 and 2 doses of JYNNEOS vaccine

▪ Highest protection provided by 2 doses, regardless of route of 

administration

▪ Further research needed to evaluate whether immunocompromised status 

modulates VE 

▪ Further research needed to understand the duration of protection
Acknowledgements

▪ Sarah Guagliardo

▪ Andrea McCollum

▪ Agam Rao

▪ Omoshalewa Bamkole

▪ David Yankey

▪ Rosalind Carter

▪ Romeo Galang

▪ Amanda Cohn

▪ Ian Kracalik

▪ Taina Joseph

▪ Anne Kimball

▪ Allie Tuttle

▪ Marie de Perio

▪ David Kuhar

▪ Jonathan Duffy

▪ Emily Faherty

▪ Ian Spicknall

▪ Chris Braden

▪ Varsha Neelam

▪ Andrew Nowalk

▪ Elizabeth Dunmore

▪ Shama Cash-Goldwasser

▪ Mukesh Hamal

▪ Marisa Hast

▪ Rebecca Free

▪ Jim Matthias