Childhood Smallpox Research Articles

A seroprevalence study indicates a high proportion of clinically undiagnosed MPXV infections in men who have sex with men in Berlin, Germany

IntroductionDuring the mpox outbreak in 2022, the highest number of cases in Germany were registered in Berlin, almost all of them in men who have sex with men (MSM). However, the frequency of clinically undiagnosed infections is unknown.MethodsA cross-sectional study was conducted among MSM in Berlin, Germany. Participants were recruited from private practices and community-based checkpoints specialised in HIV and STI care for MSM. They were asked to complete an online questionnaire on socio-demographic data, mpox diagnosis, vaccination history and sexual behaviour, and to provide a blood sample for serological analysis. The samples were tested for antibodies against a range of antigens to distinguish between antibodies induced by mpox infection and MVA vaccination, with pre-immune sera from childhood smallpox vaccination as a confounding factor. Associations of behavioural variables with reported and suspected mpox diagnosis as the outcome were tested using univariable and multivariable logistic regression models.ResultsBetween the 11th April and 1st July 2023, 1,119 participants were recruited in eight private practices and two community-based checkpoints in Berlin. All participants provided a blood sample for serological testing. Information for the online questionnaire was provided by 728 participants; core data on age and mpox history for participants who did not provide questionnaire data were provided by the practices for an additional 218 participants. A previous diagnosis of mpox was reported for/by 70 participants (7.4%). Using a conservative and strict case definition, we serologically identified an additional 91 individuals with suspected undiagnosed mpox infection. Individuals with reported or suspected mpox infections reported more condomless anal sex partners in the past 3 months (OR = 5.93; 95% CI 2.10-18.35 for 5–10 partners; OR = 9.53; 95% CI 2.72–37.54 for > 10 partners) and were more likely to report sexual contact with partners diagnosed with mpox (OR = 2.87; 95% CI 1.39–5.84).ConclusionA substantial proportion of mpox infections were clinically undiagnosed. The number of condomless anal sex partners was strongly associated with both confirmed and suspected undiagnosed mpox infection. Therefore, mpox control measures based on clinical diagnosis of mpox are likely to have limited effectiveness in preventing mpox transmission in outbreak situations because many infections remain unrecognised and undiagnosed.

Mpox-specific immune responses elicited by vaccination or infection in people living with HIV.

In the recent mpox outbreak, people living with HIV (PLWH) were at high risk both for contracting infection and for suffering a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PLWH) or smallpox vaccination (n = 17; all PLWH) in a cohort of men who have sex with men. All PLWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. 11/17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both two-dose MVA-vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination mediated cross-reactivity to other orthopox viruses, and the long-lasting durability of childhood smallpox vaccination mediated immune responses including in PLWH.

Epidemiologic and Clinical Features of Mpox in Adults Aged >50 Years - United States, May 2022-May 2023.

During May 2022-May 2023, approximately 30,000 mpox cases were reported in the United States, predominantly among young adult men. Persons aged >50 years might experience more severe mpox disease because of a higher prevalence of comorbidities. Conversely, they could have residual protection from childhood smallpox vaccination against monkeypox virus infection and severe mpox, as has been suggested by investigation of some previous mpox outbreaks. To examine the characteristics of mpox cases among adults aged >50 years, analysts compared mpox epidemiology and clinical outcomes among all adults aged ≥18 years, by age group. Further, outcomes were compared among adults aged >50 years by JYNNEOS vaccination status. During May 10, 2022-May 17, 2023, among 29,984 adults with probable or confirmed mpox reported to CDC, 2,909 (9.7%) were aged >50 years, 96.3% of whom were cisgender men. Compared with adults aged 18-50 years, adults aged >50 years had higher prevalences of immunocompromising conditions (p<0.001) and HIV infection (p<0.001). Among adults with mpox aged >50 years, 27.6% had received JYNNEOS vaccination; this group had lower prevalences of constitutional symptoms (p<0.001), pruritus (p<0.001), and hospitalization (p = 0.002) compared with those who had not received JYNNEOS vaccine. Currently recommended JYNNEOS vaccination among all adults at risk for mpox should be encouraged, irrespective of childhood smallpox vaccination status.

Modified vaccinia Ankara–Bavarian Nordic vaccine against mpox in children

Modified vaccinia Ankara–Bavarian Nordic vaccine against mpox in children

Characteristics of confirmed mpox cases among clinical suspects: A prospective single-centre study in Belgium during the 2022 outbreak

BackgroundThe presentation of mpox clade IIb during the 2022 outbreak overlaps with a range of other diseases. Understanding the factors associated with mpox is important for clinical decision making. MethodsWe described the characteristics of mpox patients who sought care at Belgian sexual health clinic. Furthermore we compared their characteristics to those of patients with a clinical suspicion of mpox but who tested negative on polymerase chain reaction. ResultsBetween May 23 and September 20, 2022, 155 patients were diagnosed with mpox, and 51 patients with suspected symptoms tested negative. All mpox patients self-identified as men and 148/155 (95.5%) as gay or bisexual MSM. Systemic symptoms were present in 116/155 (74.8%) patients. All but 10 patients (145/155, 93.5%) presented with skin lesions. Other manifestations were lymphadenopathy (72/155, 46.5%), proctitis (50/155, 32.3%), urethritis (12/155, 7.7%), tonsillitis (2/155, 1.3%). Complications involved bacterial skin infection (13/155, 8.4%) and penile oedema with or without paraphimosis (4/155, 2.6%). In multivariable logistic regression models, the presence of lymphadenopathy (OR 3.79 95% CI 1.44–11.49), skin lesions (OR 4.35 95% CI 1.15–17.57) and proctitis (OR 9.41 95% CI 2.72–47.07) were associated with the diagnosis of mpox. There were no associations with age, HIV status, childhood smallpox vaccination, number of sexual partners and international travel. ConclusionsThe presence of proctitis, lymphadenopathies and skin lesions should increase clinical suspicion of mpox in patients with compatible symptoms.

Sexual behaviours and clinical course of human monkeypox in Spain

Sexual behaviours and clinical course of human monkeypox in Spain

Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus-Infected Women Despite Immune Reconstitution With Antiretroviral Therapy.

It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections. We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA). There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24-108 years; P = .001). Despite antiretroviral therapy-associated improvement in CD4+ T-cell counts (nadir, <200/μL; >350/μL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.

Reading Memoirs of a Woman of Pleasure against Cleland’s Life and Letters

Our essay documents some of the issues we faced as modern editors of John Cleland’s Memoirs of a Woman of Pleasure (1748–49). We were conscious of the groundbreaking earlier editions of Peter Sabor and Peter Wagner, and also of the particular difficulties posed by editing a text that was both the author’s first literary work and one that he subsequently repudiated. Our edition argues for the continuity of this early text with some of the concerns that become evident in Cleland’s later life and writings. In particular, we explore some of the novel’s many references to the physical health of its characters, such as Fanny’s mild smallpox in childhood, Mr. Norbert’s “flimsy consumptive texture,” and Mr. Crofts’s aggressive sexual impotence. We see these facets of the novel as being consistent with Cleland’s regular concern, evident from his letters, for the health of his friends, and his authorship in 1761 of the Institutes of Health, which details how individual well-being could be promoted by exercise, hygiene, and a good diet.

Immunity from Smallpox Vaccine Persists for Decades: A Longitudinal Study

Purpose The threat of smallpox resulting from bioterrorist action has prompted a reassessment of the level of immunity in current populations. Methods We have examined the magnitude and duration of antiviral antibody immunity conferred by smallpox vaccination in 246 participants of the Baltimore Longitudinal Study of Aging. Of this population, 209 subjects were vaccinated one or more times 13 to 88 years before this evaluation, and stored serum samples were available at various intervals after vaccination. An additional 8 subjects who had documented childhood smallpox infection and 29 subjects with no history of infection or vaccination were included. We quantified the total vaccinia IgG and neutralizing antibody titers in each of these subgroups of participants over time. Results Vaccinated participants maintained antivaccinia IgG and neutralizing antibody titers above 3 natural logs essentially indefinitely. The absolute titer of antivaccinia antibody was only slightly higher after multiple vaccinations. In 97% of the participants, no decrease in vaccinia-specific antibody titers was noted with age over a follow-up period of up to 88 years. Moreover, Baltimore Longitudinal Study of Aging participants who survived active smallpox infections in their youth retained antivaccinia antibody titers that were similar to the levels detected in vaccinated subjects. Conclusion These data suggest that multiple or recent vaccinations are not essential to maintain vaccinia-specific antibody responses in human subjects. Scarce vaccine supplies should be applied first to individuals who have not previously been vaccinated.

Duration of Humoral Immunity to Common Viral and Vaccine Antigens

Amanna IJ, Carlson NE, Slifka MK. N Engl J Med. 2007;357(19):1903–1915 PURPOSE OF THE STUDY. To better define the duration of humoral immunity and the role played by memory B cells. STUDY POPULATION. There were 45 human subjects followed for up to 26 years. These participants were recruited from the Oregon National Primate Research Center. The only inclusion criteria was that subjects had at least 3 serum samples banked for at least 3 years before the study began. The average age at the start and end of the study was 37 and 52 years, respectively. METHODS. Blood samples were drawn at least annually, and serum was banked. Antibody titers were measured to vaccinia, measles, mumps, rubella, varicella-zoster, Epstein-Barr, tetanus, and diphtheria. Each subject gave an average of 14 serum samples over an average of 15.2 years. Also, the investigators measured antigen-specific memory B cells by means of limiting-dilution analysis and compared memory B-cell frequencies to their corresponding serum antibody levels. The majority of subjects had vaccination to smallpox in childhood and had recovered from the other viral diseases such as measles and rubella. RESULTS. The antibody responses to viral antigens were very stable, with estimated half-lives ranging from 50 years for varicella-zoster to &amp;gt;200 years for measles and mumps. Against tetanus and diphtheria, the antibody responses waned more rapidly with half-lives of 11 and 19 years, respectively. The investigators also found that B-cell memory was long-lived, but there was no significant correlation between peripheral memory B-cell numbers and antibody levels for 5 of the 8 antigens. CONCLUSIONS. Serologic memory for multiple antigens is maintained for remarkably sustained periods of time. Also, memory B-cell numbers did not correlate with antibody titers, which suggests that peripheral memory B-cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of immunity. REVIEWER COMMENTS. At the end of the study, the average age of the participants was 52 years. Most had received vaccination to smallpox, but most had also contracted natural measles, mumps, or rubella during childhood. This study population, therefore, does not represent our current population of children with complex schedules of vaccinations. Furthermore, we cannot conclude from this study that vaccination-induced immunity is necessarily as long-lived as natural infection-induced immunity. Nonetheless, this report does give fascinating insight into the “adult” side of immunity to many of the childhood diseases against which we vaccinate. This study also sheds light on possible mechanisms for sustained humoral immunity, which it seems may not entirely depend on regulation by memory B cells.

Monkeypox-Induced Immunity and Failure of Childhood Smallpox Vaccination To Provide Complete Protection

Following the U.S. monkeypox outbreak of 2003, blood specimens and clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to evaluate the role of preexisting (smallpox vaccine-derived) and acquired immunity in susceptibility to monkeypox disease and clinical outcomes. Orthopoxvirus-specific immunoglobulin G (IgG), IgM, CD4, CD8, and B-cell responses were measured at approximately 7 to 14 weeks and 1 year postexposure. Associations between immune responses, smallpox vaccination, and epidemiologic and clinical data were assessed. Participants were categorized into four groups: (i) vaccinated cases, (ii) unvaccinated cases, (iii) vaccinated contacts, and (iv) unvaccinated contacts. Cases, regardless of vaccination status, were positive for orthopoxvirus-specific IgM, IgG, CD4, CD8, and B-cell responses. Antiorthopoxvirus immune responses consistent with infection were observed in some contacts who did not develop monkeypox. Vaccinated contacts maintained low levels of antiorthopoxvirus IgG, CD4, and B-cell responses, with most lacking IgM or CD8 responses. Preexisting immunity, assessed by high antiorthopoxvirus IgG levels and childhood smallpox vaccination, was associated (in a nonsignificant manner) with mild disease. Vaccination failed to provide complete protection against human monkeypox. Previously vaccinated monkeypox cases manifested antiorthopoxvirus IgM and changes in antiorthopoxvirus IgG, CD4, CD8, or B-cell responses as markers of recent infection. Antiorthopoxvirus IgM and CD8 responses occurred most frequently in monkeypox cases (vaccinated and unvaccinated), with IgG, CD4, and memory B-cell responses indicative of vaccine-derived immunity. Immune markers provided evidence of asymptomatic infections in some vaccinated, as well as unvaccinated, individuals.

Smallpox vaccination and risk of allergy and asthma

Background: It has been proposed that childhood vaccinations may influence the development of allergy. Atopy and allergic diseases have increased after routine smallpox vaccination was stopped in the 1970s. Objective: We examined whether administration of smallpox vaccination during childhood was associated with a decreased risk of atopy, allergic rhinitis, and asthma. Methods: The occurrence of atopy, allergic rhinitis, and asthma was studied in nearly 2000 women participating in a national birth cohort study. Detailed information on smallpox vaccination was available from school health records. Atopic status was assessed serologically by a specific response to 11 common inhalant allergens by using serum samples obtained from the women during the period 1997 to 2001. Information on allergic rhinitis and asthma was available from telephone interviews. Results: We found no association between having been vaccinated against smallpox in childhood and risk of atopy or allergic rhinitis. Smallpox vaccination was associated with a slightly decreased risk of asthma. There was no association between age at smallpox vaccination and risk of atopy, allergic rhinitis, or asthma. Adjusting for birth cohort, sibship size, age of the woman's mother at birth, and social class in childhood did not change these results. Conclusion: Our findings do not suggest that childhood vaccination against smallpox, even if given early in life, influences the development of atopy or allergic rhinitis. The association with asthma should be interpreted with caution and needs further study. (J Allergy Clin Immunol 2003;111:1227-31.)

Human cytotoxic T-cell memory: long-lived responses to vaccinia virus.

Peripheral T lymphocytes can be classified into two groups: naive and memory T cells. The focus of this study was to examine the duration of T-cell memory in humans. Vaccinia virus replicates in the cytoplasm of infected cells and is not thought to persist or become latent after the acute phase of infection. We identified long-lived vaccinia virus-specific memory cytotoxic T cells in adults who had been immunized against smallpox as children. Initially, we detected vaccinia virus-specific T cells in peripheral blood mononuclear cells while screening for human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses in HIV-1-seropositive subjects. These individuals had not had contact with vaccinia virus since their primary immunization in early childhood. Several vaccinia virus-specific CD4+ T-cell clones were derived from these donors and characterized. Healthy, HIV-1-seronegative donors who had been immunized against smallpox many (35 to 50) years earlier were also screened for vaccinia virus-specific T-cell immunity. We found significant CD8+ and CD4+ cytotoxic T-cell responses to vaccinia virus after in vitro stimulation, indicating that these memory cells are maintained in vivo for many years. The peripheral blood mononuclear cells of young adults with no history of immunization against smallpox did not develop vaccinia virus-specific T-cell responses after in vitro stimulation. Precursor frequency analysis of the vaccinia virus-specific memory CD4+ T cells from a donor immunized with vaccinia virus 35 years earlier revealed a frequency of 1 in 65,920 CD4+ T cells. We concluded that specific vaccinia virus T-cell immunity can persist for up to 50 years after immunization against smallpox in childhood in the presumed absence of exposure to vaccinia virus.

End of routine smallpox vaccination in childhood.

Editorial Notes1 February 1972End of Routine Smallpox Vaccination in ChildhoodWILLIAM H. FOEGE, M.D., J. MICHAEL LANE, M.D.WILLIAM H. FOEGE, M.D.Search for more papers by this author, J. MICHAEL LANE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-2-324 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn October 1971 the United States Public Health Service recommended the cessation of routine childhood smallpox vaccination. This decision was reached after several years of study and was based on a number of considerations.The World Health Organization's global smallpox eradication program has been highly successful and is expected to reach its objective of a smallpox-free world by 1976. Only eight countries still remain endemic for smallpox, and several of the eight are currently reaching a smallpox-free state.Largely because of the dramatic decrease in smallpox-endemic areas, the likelihood that smallpox will be imported to the United States has decreased... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Center for Disease Control Atlanta, Ga. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe discontinuation of routine smallpox vaccination in the United States, 1960-1976: an unlikely affirmation of biomedical hegemony 1 February 1972Volume 76, Issue 2Page: 324-325KeywordsGlobal healthMedical services Issue Published: 1 February 1972 PDF DownloadLoading ...

The case for continuing "routine" childhood smallpox vaccination in the United States.

The case for continuing "routine" childhood smallpox vaccination in the United States.

The case for abolishing routine childhood smallpox vaccination in the United States.

The case for abolishing routine childhood smallpox vaccination in the United States.

Routine childhood vaccination against smallpox reconsidered.

Abstract The United States can expect 210 deaths caused by smallpox vaccination between now and the end of the century if present policies, emphasizing routine childhood vaccination, persist. The risk of importation of smallpox is extremely low. Only two out of every three importations have resulted in spread, and only eight deaths on the average have occurred in each outbreak. To outweigh the health hazards of routine vaccination, the United States would have to have a smallpox importation nearly every year. The benefits of routine childhood smallpox vaccination no longer outweigh its risks, and consideration should be given to its discontinuance.