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P-1312. MPox Seroprevalence and Seroincidence among People who Inject Drugs in the Mexico-U.S. Border Region

Abstract Background We assessed seroprevalence and seroincidence against orthopoxvirus (OPXV) among people who inject drugs (PWID) in the U.S./Mexico border region during the COVID-19 pandemic. Methods Between 09/21-11/23, PWID who lived in either San Diego (SD; N=129) or Tijuana (TJ; N=343) underwent a baseline and follow-up visit involving interviewer-administered surveys and venipuncture. Sera were batch tested at the U.S. Center for Disease Control and Prevention using an OPXV generic IgG ELISA using JYNNEOS® vaccine as the viral antigen. Optical densities (OD) ≥0.1 were conservatively considered seropositive. Mpox seroprevalence was assessed after excluding known sources of anti-OPXV antibodies Results Of 472 participants enrolled, median age was 45 (IQR:38-53), 72.9% were male (3.2% of whom reported sex with men), 11.3% had HIV and 25.8% were unhoused. Although no symptoms consistent with Mpox were reported during the study, 50 (10.6%) had seropositive results at baseline, follow-up or both. Baseline OPXV seroprevalence was 19.4% in SD and 3.2% in TJ, and Mpox seroincidence was 8.97 (95%CI:4.09-13.85) per 100 person-years in TJ vs. 1.81 (95%CI: 0.00-5.35) in SD, with a median of 5.8 months of follow-up (IQR: 4.53 – 6.31 months). Excluding participants who reported Mpox vaccination (N=3), smallpox vaccination (N=73), or those born prior to 1971 who could have received smallpox vaccination (N=140), likely Mpox seroprevalence was 7.8% (23/296), with 13/23 seronegative at baseline but seropositive at follow-up. Of these 13 seroconveters, 5 were female of whom 2 were HIV+. Conclusion These preliminary data suggest a undetected Mpox circulation in the Mexico-U.S. border region between 2022 and 2023 and that asymptomatic or mildly symptomatic Mpox infection may be more common than previously recognized. Although the clinical implications of these findings remain unclear, expansion of Mpox vaccination to PWID may be warranted. Disclosures David Smith, MD, MAS, Bayer: Advisor/Consultant|Gilead: Advisor/Consultant|Model Medicines: Advisor/Consultant|Red Queen Therapuetics: Advisor/Consultant

Effectiveness of historical smallpox vaccination against mpox clade II in men in Denmark, France, the Netherlands and Spain, 2022.

BackgroundIn 2022, a global monkeypox virus (MPXV) clade II epidemic occurred mainly among men who have sex with men. Until early 1980s, European smallpox vaccination programmes were part of worldwide smallpox eradication efforts. Having received smallpox vaccine > 20 years ago may provide some cross-protection against MPXV.AimTo assess the effectiveness of historical smallpox vaccination against laboratory-confirmed mpox in 2022 in Europe.MethodsEuropean countries with sufficient data on case vaccination status and historical smallpox vaccination coverage were included. We selected mpox cases born in these countries during the height of the national smallpox vaccination campaigns (latest 1971), male, with date of onset before 1 August 2022. We estimated vaccine effectiveness (VE) and corresponding 95% CI for each country using logistic regression as per the Farrington screening method. We calculated a pooled estimate using a random effects model.ResultsIn Denmark, France, the Netherlands and Spain, historical smallpox vaccination coverage was high (80-90%) until the end of the 1960s. VE estimates varied widely (40-80%, I2 = 82%), possibly reflecting different booster strategies. The pooled VE estimate was 70% (95% CI: 23-89%).ConclusionOur findings suggest residual cross-protection by historical smallpox vaccination against mpox caused by MPXV clade II in men with high uncertainty and heterogeneity. Individuals at high-risk of exposure should be offered mpox vaccination, following national recommendations, regardless of prior smallpox vaccine history, until further evidence becomes available. There is an urgent need to conduct similar studies in sub-Saharan countries currently affected by the MPXV clade I outbreak.

Sexual orientation was associated with intention to be vaccinated with a smallpox vaccine against mpox: A cross-sectional preliminary survey in Japan

This survey aimed to assess the prevalence of intention to receive smallpox vaccine against mpox and its relationship with sexual orientation in Japan. A cross-sectional online survey was conducted in September-October 2022, with 12,900 assigned males and 13,413 assigned females participating. Modified Poisson regression analyses were performed to determine the relationship between vaccine willingness and sexual orientation, adjusting for socioeconomics, trust in government, COVID-19 vaccination status, and frequency of brothel visits. Vaccine willingness was higher in homosexual respondents than heterosexual counterparts, with proportions of 23.1 % among assigned males and 13.4 % among assigned females. Homosexual orientation was significantly associated with vaccine willingness, with prevalence ratios of 1.37 (95 % CI: 1.23–1.54) among assigned males and 1.34 (95 % CI: 1.13–1.59) among assigned females. These findings highlight the need for targeted vaccine promotion campaigns and ongoing monitoring of attitudes towards mpox and vaccine compliance in high-risk groups.

Clinical and Epidemiological Findings from Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo During 2011-2015.

Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of polymerase chain reaction-confirmed cases by sex and age. We report 1057 confirmed cases. The average annual incidence was 14.1 per 100 000 (95% confidence interval, 13.3-15.0). The incidence was higher in male patients (incidence rate ratio comparing males to females, 1.21; 95% confidence interval, 1.07-1.37), except among those 20-29 years old (0.70; .51-.95). Females aged 20-29 years also reported a high frequency of exposures (26.2%) to people with monkeypox-like symptoms.The highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37.5%). The incidence was lower among those presumed to have received smallpox vaccination than among those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow sociocultural norms.

IMVAMUNE® and ACAM2000® Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model.

The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today’s populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 104 pfu (2× LD50) or 106 pfu (170× LD50) and vaccinated the animals with IMVAMUNE® or ACAM2000® either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD50, but not the 170× LD5 challenge. In the 2× LD50 challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE®, but ACAM2000® was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented.

Asymptomatic Orthopoxvirus Circulation in Humans in the Wake of a Monkeypox Outbreak among Chimpanzees in Cameroon.

.Monkeypox virus is a zoonotic Orthopoxvirus (OPXV) that causes smallpox-like illness in humans. In Cameroon, human monkeypox cases were confirmed in 2018, and outbreaks in captive chimpanzees occurred in 2014 and 2016. We investigated the OPXV serological status among staff at a primate sanctuary (where the 2016 chimpanzee outbreak occurred) and residents from nearby villages, and describe contact with possible monkeypox reservoirs. We focused specifically on Gambian rats (Cricetomys spp.) because they are recognized possible reservoirs and because contact with Gambian rats was common enough to render sufficient statistical power. We collected one 5-mL whole blood specimen from each participant to perform a generic anti-OPXV ELISA test for IgG and IgM antibodies and administered a questionnaire about prior symptoms of monkeypox-like illness and contact with possible reservoirs. Our results showed evidence of OPXV exposures (IgG positive, 6.3%; IgM positive, 1.6%) among some of those too young to have received smallpox vaccination (born after 1980, n = 63). No participants reported prior symptoms consistent with monkeypox. After adjusting for education level, participants who frequently visited the forest were more likely to have recently eaten Gambian rats (OR: 3.36, 95% CI: 1.91–5.92, P < 0.001) and primate sanctuary staff were less likely to have touched or sold Gambian rats (OR: 0.23, 95% CI: 0.19–0.28, P < 0.001). The asymptomatic or undetected circulation of OPXVs in humans in Cameroon is likely, and contact with monkeypox reservoirs is common, raising the need for continued surveillance for human and animal disease.

Phase-out of smallpox vaccination and the female/male HIV-1 prevalence ratio: an ecological study from Guinea-Bissau

ObjectiveIn Guinea-Bissau, West Africa, we observed that having a smallpox vaccination scar was associated with lower HIV-1 prevalence, more strongly for women than men. If this represents a causal effect,...

Position on reproductive donors and smallpox vaccine: a committee opinion

Although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, the Society for Assisted Reproductive Technology (SART) and the American Society for Reproductive Medicine (ASRM) accordingly recommend that assisted reproductive technology (ART) practitioners consider deferring individuals who are planning on donating gametes for reproductive use (reproductive donors) who have recently received smallpox vaccine or contracted symptomatic vaccinia virus infection through close contact with a vaccine recipient (until after the vaccine or infectious scab has spontaneously separated). Good donor practice further suggests that reproductive donors who are not in good health, including those with recent complications from smallpox vaccine, should be similarly deferred. This document replaces the previous document of the same name last published in 2012 (Fertil Steril 2012;98:e1-e2).

Polyfunctional T Cell and Neutralizing Antibody Responses to ACAM2000&amp;lt;sup&amp;gt;TM&amp;lt;/sup&amp;gt; Smallpox Vaccine Immunization in Primary-Vaccinated Individuals

Smallpox eradication was successful via prophylactic administration of live attenuated vaccinia virus. As a result of the discontinuation of the smallpox immunization program, many individuals are now susceptible to smallpox virus infection should it be used as a biological weapon. Presently, only individuals at high risk for exposure are required to receive smallpox vaccine, such as laboratory personnel that handle variola/vaccinia virus. This study endeavored to investigate a one-year period of vaccinia virus-specific T cell responses using polychromatic flow cytometry and neutralizing (Nt) antibody responses using plaque reduction neutralization test (PRNT) in individuals receiving primary immunization (n = 5) with ACAM2000TM smallpox vaccine. Functional and phenotypic profiles of vaccinia virus-specific T cell responses were characterized. Each single functional measurement {CD107a/b expression, production of interferon g (IFN-g), macrophage inflammatory protein 1b (MIP-1b), interleukin 2 (IL-2), and tumor necrosis factor a (TNF-a)} demonstrated that vaccinia virus-specific CD8+ T cells were functional at least one time point after vaccination (p ≤ 0.05). However, vaccinia virus-specific CD4+ T cells were functional only for MIP-1b production (p ≤ 0.05). Vaccinia virus-specific CD8+ T cells induced in these individuals showed increased polyfunctionality in at least 2 phenotypes relative to pre-vaccination (p ≤ 0.05). Although only three of five individuals (60%) showed positive Nt antibody (titer ≥ 20) at first month after vaccination, all five individuals (100%) demonstrated Nt antibody at 2 months, post-immunization. Interestingly, all vaccinees could retain the Nt antibody for 6 months after primary vaccination. In conclusion, ACAM2000TM smallpox vaccine induced both polyfunctional T cell-and Nt antibody-responses in primary immunized individuals.

Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed

The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy.

Smallpox vaccine, ACAM2000: Sites and duration of viral shedding and effect of povidone iodine on scarification site shedding and immune response

The U.S. Department of Defense vaccinates personnel deployed to high-risk areas with the vaccinia virus (VACV)-based smallpox vaccine. Autoinoculations and secondary and tertiary transmissions due to VACV shedding from the vaccination site continue to occur despite education of vaccinees on the risks of such infections. The objectives of this study were to investigate, in naïve smallpox vaccinees, (a) whether the vaccination site can remain contagious after the scab separates and (b) whether the application of povidone iodine ointment (PIO) to the vaccination site inactivates VACV without affecting the immune response. These objectives were tested in 60 individuals scheduled to receive smallpox vaccine. Thirty individuals (control) did not receive PIO; 30 subjects (treatment) received PIO starting on post-vaccination day 7. Counter to current dogma, this study showed that VACV continues to shed from the vaccination site after the scab separates. Overall viral shedding levels in the PIO group were significantly lower than those in the control group (p=0.0045), and PIO significantly reduced the duration of viral shedding (median duration 14.5 days and 21 days in the PIO and control groups, respectively; p=0.0444). At least 10% of control subjects continued to shed VACV at day 28, and 3.4% continued to shed the virus at day 42. PIO reduced the proportion of subjects shedding virus from the vaccination site from day 8 until days 21–23 compared with control subjects. Groups did not differ significantly in the proportion of subjects mounting an immune response, as measured by neutralizing antibodies, IgM, IgG, and interferon-gamma enzyme-linked immunospot assay. When applied to the vaccination site starting on day 7, PIO reduced viral shedding without altering the immune response. The use of PIO in addition to a semipermeable dressing may reduce the rates of autoinoculation and contact transmission originating from the vaccination site in smallpox-vaccinated individuals.

Impact of infection or vaccination on pre-existing serological memory

Once established, serum antibody responses against a specific pathogen may last a lifetime. We describe a cohort of four subjects who received smallpox vaccination, and a single subject who received multiple vaccinations, with antibody levels to unrelated antigens monitored for 1-3 years. These immunizations provided the opportunity to determine if infection/vaccination and the resulting toll-like receptor stimulation would alter antigen-specific serological memory to other antigens, including bacterial toxins (tetanus, diphtheria, and pertussis) and viruses (yellow fever virus, measles, mumps, rubella, Epstein-Barr virus, and varicella-zoster virus). Our results indicate that serum IgG levels are remarkably stable and infection or vaccination are unlikely to increase or decrease pre-existing antigen-specific antibody responses.

Position on donors and smallpox vaccine: a committee opinion

Although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, SART/ASRM accordingly recommends that ART practitioners consider deferring donors who have recently received smallpox vaccine or contracted symptomatic vaccinia virus infection through close contact with a vaccine recipient (until after the vaccine or infectious scab has spontaneously separated). Good donor practice further suggests that donors who are not in good health, including those with recent complications from smallpox vaccine, should be similarly deferred. (This document was reviewed by the ASRM Practice Committee in 2011).

INCIDENCE OF MYOCARDITIS/PERICARDITIS FOLLOWING SMALLPOX VERSUS INFLUENZA VACCINATION

Over 2 million U.S. servicemembers have received smallpox vaccination (SPX) since December 2002. There is limited data on the incidence of clinical myocarditis/pericarditis (MP) following SPX and potential subclinical myocarditis has not been well defined. To determine the incidence of clinical and

Smallpox vaccination and all-cause infectious disease hospitalization: a Danish register-based cohort study

There is growing evidence from observational studies and randomized trials in low-income countries that vaccinations have non-specific effects. Administration of live vaccines reduces overall child morbidity and mortality, presumably due to protection against non-targeted infections. In Denmark, the live vaccine against smallpox was phased out in the 1970s due to the eradication of smallpox. We used the phasing-out period to investigate the effect of smallpox vaccination on the risk of hospitalization for infections. From the Copenhagen School Health Records Register, a cohort of 4048 individuals was sampled, of whom 3559 had information about receiving or not receiving smallpox vaccination. Infectious disease hospitalizations were identified in the Danish National Patient Register. During 87,228 person-years of follow-up, 1440 infectious disease hospitalizations occurred. Smallpox-vaccinated individuals had a reduced risk of all-cause infectious disease hospitalization compared with smallpox-unvaccinated individuals [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.72-0.98]. The reduced risk of hospitalizations was seen for most subgroups of infectious diseases. The effect may have been most pronounced after early smallpox vaccination (vaccination age <3.5 years: HR 0.81; 95% CI 0.69-0.95; vaccination age ≥ 3.5 years: HR 0.91 95% CI 0.76-1.10). Among the smallpox-vaccinated, the risk of infectious disease hospitalization increased 6% with each 1-year increase in vaccination age (HR 1.06; 95% CI 1.02-1.10). Smallpox vaccination is associated with a reduced risk of infectious disease hospitalization in a high-income setting.

Society for Assisted Reproductive Technology position statement on donor suitability of recipients of smallpox vaccine (vaccinia virus)

Although there is presently no definitive evidence linking vaccinia virus transmission through reproductive cells, SART/ASRM accordingly recommends that ART practitioners consider deferring donors who have recently received smallpox vaccine or contracted symptomatic vaccinia virus infection through close contact with a vaccine recipient (until after the vaccine or infectious scab has spontaneously separated). Good donor practice further suggests that donors who are not in good health, including those with recent complications from smallpox vaccine, should be similarly deferred.

Evaluation of preterm births and birth defects in liveborn infants of US military women who received smallpox vaccine

Women serving in the US military have some unique occupational exposures, including exposure to vaccinations that are rarely required in civilian professions. When vaccinations are inadvertently given during pregnancy, such exposures raise special concerns. These analyses address health outcomes, particularly preterm births and birth defects, among infants who appear to have been exposed to maternal smallpox vaccination in pregnancy. This retrospective cohort study included 31,420 infants born to active-duty military women during 2003-2004. We used Department of Defense databases to define maternal vaccination and infant health outcomes. Multivariable regression models were developed to describe associations between maternal smallpox vaccination and preterm births and birth defects in liveborn infants. There were 7,735 infants identified as born to women ever vaccinated against smallpox, and 672 infants born to women vaccinated in the first trimester of pregnancy. In multivariable modeling, maternal smallpox vaccination in pregnancy was not associated with preterm or extreme preterm delivery. Maternal smallpox vaccination in the first trimester of pregnancy was not significantly associated with overall birth defects (OR 1.40; 95% CI: 0.94, 2.07), or any of seven specific defects individually modeled. Results may be reassuring that smallpox vaccine, when inadvertently administered to pregnant women, is not associated with preterm delivery or birth defects in liveborn infants.

Severe Eczema Vaccinatum in a Household Contact of a Smallpox Vaccinee

We report the first confirmed case of eczema vaccinatum in the United States related to smallpox vaccination since routine vaccination was discontinued in 1972. A 28-month-old child with refractory atopic dermatitis developed eczema vaccinatum after exposure to his father, a member of the US military who had recently received smallpox vaccine. The father had a history of inactive eczema but reportedly reacted normally to the vaccine. The child's mother also developed contact vaccinia infection. Treatment of the child included vaccinia immune globulin administered intravenously, used for the first time in a pediatric patient; cidofovir, never previously used for human vaccinia infection; and ST-246, an investigational agent being studied for the treatment of orthopoxvirus infection. Serological response to vaccinia virus and viral DNA levels, correlated with clinical events, were utilized to monitor the course of disease and to guide therapy. Burn patient-type management was required, including skin grafts. The child was discharged from the hospital after 48 days and has recovered with no apparent systemic sequelae or significant scarring. This case illustrates the need for careful screening prior to administration of smallpox vaccine and awareness by clinicians of the ongoing vaccination program and the potential risk for severe adverse events related to vaccinia virus.

The Smallpox Vaccine Injury Compensation Program

In January 2003, the Secretary of the US Department of Health and Human Services (DHHS) announced that certain individuals should receive smallpox vaccine or other countermeasures to be prepared to serve the civilian population in the event of a smallpox bioterrorism event. In April 2003, Congress passed and the President signed the Smallpox Emergency Personnel Protection Act of 2003. This act created the Smallpox Vaccine Injury Compensation Program to provide medical and lost employment income coverage as a payer of last resort to persons who sustain a covered medical injury as a direct result of receiving smallpox vaccination voluntarily under a DHHS-approved smallpox emergency response plan. As of September 2006, 62 persons had requested benefits, of whom 19 had been determined to be medically eligible, 27 were denied benefits, and 16 submitted the request after the legislatively defined filing deadline.

US Military Smallpox Vaccination Program: Occupational Impact of Immunizations on Aircrew in Air Mobility Command, US Air Force

President George W. Bush announced a national smallpox vaccination program (SVP) on December 13, 2002, for military personnel, civilian healthcare workers, and "first responders." The program was intended to protect these individuals against exposure to weaponized smallpox. The US Air Force (USAF) began implementation of the SVP on January 7, 2003. To determine if the SVP affected USAF personnel readiness, and, based on these results, to determine the overall safety of a large-scale SVP. A retrospective cohort study of duty-restriction rates measured by duties not to include flying (DNIFs) of C-17 aircrews in the USAF Air Mobility Command (AMC). Data from January 2002 to May 2002 (prevaccination) and January 2003 to May 2003 (vaccination) were compiled by month from three of the 11 AMC bases. Total DNIFs associated with or attributed to the smallpox vaccine were recorded. In addition, total 2003 DNIFs in 1662 study subjects (678 [40.8%] of whom received smallpox vaccination) were recorded and compared with total 2002 DNIFs in 1602 control subjects before SVP implementation. Differences in monthly DNIF rates were calculated using the one-tailed paired t test. In the 678 subjects who received smallpox vaccination, 13 vaccine-related DNIFs (1.9%) occurred. Differences in DNIF rates were statistically significant (P<.05) during 2 months at one AMC base. However, the SVP did not increase overall DNIF rates in the SVP study period. With DNIF status as a health marker, the SVP did not impose operational constraints or adversely affect aircrew preparedness in the USAF AMC. The authors suggest that a similar SVP with comparable screening measures would indicate the overall safety of the vaccine.