PIIS1473309923004929.pdf

Articles Mpox in people with past infection or a complete vaccination course: a global case series Aniruddha Hazra, Jason Zucker, Elizabeth Bell, John Fl...

Articles Mpox in people with past infection or a complete vaccination course: a global case series Aniruddha Hazra, Jason Zucker, Elizabeth Bell, John Flores, Leanna Gordon, Oriol Mitjà, Clara Suñer, Adrien Lemaignen, Simon Jamard, Silvia Nozza, Achyuta V Nori, Edgar Pérez-Barragán, Juan Carlos Rodríguez-Aldama, Jose Louis Blanco, Constance Delaugerre, Dan Turner, Irene Fuertes, Viviana Leiro, Sharon L Walmsley, Chloe M Orkin, on behalf of SHARE-NET writing group* Summary Background Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has Lancet Infect Dis 2024; predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially 24: 57–64 from precursors originating from the 2017–18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via Published Online September 4, 2023 previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters https://doi.org/10.1016/ were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe S1473-3099(23)00492-9 the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve See Comment page 6 the understanding of this disease in the setting of previous immunity. *Members of SHARE-NET writing group are listed in the Methods In this global case series, international collaborators from nine countries provided data on individuals with appendix (pp 2–3) PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. Section of Infectious Diseases We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received and Global Health, University of Chicago Medicine, Chicago, before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report IL, USA (A Hazra MD, E Bell MD, spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, J Flores MD); Howard Brown clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox Health, Chicago, IL, USA severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were (A Hazra, L Gordon DO); Division of Infectious Diseases, descriptive. Columbia University Irving Medical Center, New York, NY, Findings We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox USA (J Zucker MD); Skin reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Neglected Tropical Diseases and Sexually Transmitted Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection Infections section, Fight and infection after vaccination. The median age of individuals was 36 years (IQR 30–45; range 21–58). Those with Infectious Diseases natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than Foundation, Hospital Germans with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and Trias i Pujol, Badalona, Spain (O Mitjà PhD, C Suñer PhD); minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial Department of Infectious superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a Diseases, University Hospital of necrotising neck lesion. Tours, Tours, France (A Lemaignen MD, S Jamard MD); Vita-Salute Interpretation The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other San Raffaele University, published cohorts during the 2022 outbreak—predominantly young, sexually active gay and bisexual men who have Infectious Diseases Unit, sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less San Raffaele Scientific Institute, Milan, Italy clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these (S Nozza MD); Guy’s and individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia St Thomas’ NHS Foundation requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against Trust, London, UK mpox infection. However, in this small series both disease duration and severity appear to be reduced. (A V Nori MD); Clinica Especializada Condesa Iztapalapa, Mexico City, Mexico Funding None. (E Pérez-Barragán MD, J C Rodríguez-Aldama MD); Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC Infectious Diseases Department, Hospital Clínic de license. Barcelona, Barcelona University, Barcelona, Spain Introduction sexually active gay, bisexual, and other men who have sex (Prof J L Blanco PhD); Service de Since May, 2022, more than 87 000 cases of human mpox with men; transmissions have been associated with skin- Virologie, Hôpital Saint-Louis, AP–HP, Université Paris Cité, (formerly known as monkeypox) have been reported in to-skin and bodily fluid contact because human monkeypox Paris, France 111 countries, leading to WHO declaring mpox a Public virus (hMPXV) has been isolated from seminal, rectal, (Prof C Delaugerre PhD); Crusaid Health Emergency of International Concern (PHEIC) in and vaginal secretions.3,4 Infections in cisgender and Kobler AIDS Center, Tel-Aviv July, 2022.1,2 Unlike previously described outbreaks in transgender women have also been described.5 Sourasky Medical Center, Sackler Faculty of Medicine, historically affected countries, transmissions in the current With respect to other orthopoxviruses, infection with Tel-Aviv University, Tel-Aviv, multi country outbreak have predominantly affected the variola virus is known to confer lifelong immunity www.thelancet.com/infection Vol 24 January 2024 57  Articles Israel (D Turner MD); Dermatology Department, Research in context Hospital Clinic, Barcelona, Spain (I Fuertes PhD); Evidence before this study the severity scores documented earlier in the 2022 outbreak, Dermatology Department, Since May, 2022, mpox (formerly known as monkeypox), the infections we described scored lower and were less Hospital Muñiz, Buenos Aires, a disease caused by the orthopoxvirus human monkeypox virus extensive. When clinical features of a cases’ repeat infections Argentina (V Leiro MD); (hMPXV), has caused outbreaks in 111 countries. Clade IIb, were compared with their first infections, these were also University Health Network, University of Toronto, Toronto, newly identified during the 2022 outbreak, has originated from milder in severity. This assessment was based on reduction in ON, Canada subclade IIa but differs substantially both phylogenetically and mucosal involvement, confluence of lesions, analgesia (Prof S L Walmsley MD); Blizard clinically. Unlike previously epidemiological descriptions in requirement, and bacterial superinfection. Additionally, there Institute and SHARE Collaborative, Queen Mary historically affected countries, sexual networks of gay and were fewer hospitalisations than in several large case series University of London, London, bisexual men who have sex with men have been already published. We also described one individual who UK (Prof C M Orkin MD); disproportionately affected during the current global outbreak. received a complete vaccination course who went on to have a Department of Infection and hMPXV has been isolated in semen as well as rectal and vaginal first infection 4 days later and a presumed second infection Immunity, Barts Health NHS Trust, London, UK secretions and has shown to be replication-competent in the 266 days later following a documented mpox exposure. (Prof C M Orkin) anorectum. Clear evidence of asymptomatic rectal carriage as Implications of all the available evidence Correspondence to: well as case-pair data showing infectivity 4 days before Our findings support the consideration that neither natural Prof Chloe M Orkin, Blizard symptom onset further strengthens the argument that mpox Institute and SHARE immunity from an initial mpox infection nor post-vaccination behaves as a sexually transmitted infection in the conventional Collaborative, Queen Mary immunity are completely protective against the Clade IIb virus. sense. Some cases of repeat infections and infections after University of London, However, the immunity from both appears to be of benefit in London E1 2AT, UK vaccination were reported in early 2023 in Europe and the terms of limiting the most severe disease. Clinicians should be [email protected] Americas. Additionally, one case of phylogenetically confirmed aware that previous infection and vaccination do not preclude See Online for appendix reinfection has been described in detail. Taken together these mpox infection and they should maintain vigilance in making findings warrant careful evaluation of the interplay between the diagnosis when clinical suspicion exists. Our small series natural immunity and vaccine-induced immunity and reinforces the importance of vaccination and supports the reinfection with Clade IIb hMPXV. We searched PubMed for the recommendations that all people vulnerable to hMPXV terms “monkeypox, mpox AND (reinfection)” from infection should be prioritised for preventive mpox vaccination. May 11, 2022, to June 18, 2023. Publications were This approach requires vaccines to be globally available in the predominantly letters, perspectives, case reports, and public countries historically affected by mpox and newly affected health agency reports. So far, case series of people with countries that still have no such access. Our study also reinfection or infection post-vaccination have not come from reinforces that there is still much to learn about immunity with more than a single centre or city and none have used a respect to the Clade IIb virus and ongoing phylogenetic, standardised severity scoring system to compare illness. immunological, case-control, and randomised trial research is Added value of this study urgently needed. These efforts will need to include the This mpox case series is the largest and only series to describe collection of samples for virus isolation and sequencing to both reinfections and infections after a complete vaccine distinguish reinfection from relapse. There is also a need to course of Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN). bolster public health surveillance so that cases of suspected Notably, both natural and post-vaccination immunity is relapse, reinfection, and breakthrough infection should be considered lifelong in smallpox. Similarly, in Clade I and IIa notified to the relevant public health agencies to further inform mpox infections, reinfections, and post-vaccine infections have policies and guidelines. How to safely protect not been clearly described. We characterised 37 people with immunosuppressed people, including people with advanced either reinfection after a previous infection in 2022, or an HIV disease, through vaccination is also a highly relevant area infection at least 14 days after a correctly administered for research and for policy makers. complete course of MVA-BN since May, 2022. Compared with and the vaccinia virus vaccine is more than 95% effective Clade IIb virus is also unclear. During the multicountry in preventing smallpox infection.6 Data from the outbreak, several case reports have been published multicountry outbreak have shown that hMPXV describing possible mpox reinfection.10–14 Although not stimulates a robust immune response; this finding all infections have been confirmed through viral culture suggests that the benefit of vaccination within a year of or phylogenetic sequencing, resolution of symptoms infection might be limited.7 Cases of non-Clade IIb with interim negative mpox testing has been described mpox infections after childhood smallpox vaccination in all cases. This finding is more clinically consistent have been described previously.8,9 So, the durability the with reinfection than relapse; however, the relapse protective immunity from either a previous infection or cannot be completely excluded based on the evidence vaccination is worthy of further study. Furthermore, presented. One case of reinfection has been well any possible role for viral persistence or latency in described 3 months after initial infection in 58 www.thelancet.com/infection Vol 24 January 2024  Articles an un­ vaccinated person with subtype IIb, lineage Methods B.1 virus on both occasions based on whole-genome Study design sequencing.10 There is also evidence of other clades In response to new mpox case clusters disproportionately currently in circulation, raising further concerns affecting people with presumed immunity, academic regarding re­infection.15 researchers within the London-based Sexual Health and Pre-exposure and post-exposure vaccination pro­ HIV All East Research (SHARE) Collaborative (London, grammes have been a crucial part of the mpox response UK) renewed the international collaboration, SHARE- in North America and Europe. ACAM2000 (Sanofi Net, co-led by the Section of Infectious Diseases and Pasteur Biologics), a second-generation, replication- Global Health at the University of Chicago (Chicago, IL, competent, single-dose smallpox vaccine and Modified USA). Researchers globally in locations with high Vaccinia Ankara Vaccine-Bavarian Nordic (MVA-BN; also known as IMVANEX, IMVAMUNE, or JYNNEOS), Total number of Mpox case after Mpox case after a third-generation, non-replicating, two-dose smallpox individuals* (n=37) past infection (n=8) vaccination (n=30) vaccine have been authorised for prevention of mpox in WHO region adults with MVA-BN predominantly being used Region of the Americas 21/37 (57%) 5/8 (63%) 17/30 (57%) currently. Although the effectiveness of ACAM2000 in European region 16/37 (43%) 3/8 (37%) 13/30 (43%) preventing mpox has not been established, multiple Age, years 36 (30–45); 21–58 35 (31–37); 27–48 37 (30–45); 21–58 studies have confirmed some degree of immunogenicity and a single study showed protection against mpox Gender using its first-generation precursor, Dryvax (Wyeth Cisgender male 37/37 (100%) 8/8 (100%) 30/30 (100%) Laboratories).16,17 Throughout the current outbreak, Sexual orientation effectiveness of MVA-BN has been studied largely Gay 36/37 (97%) 8/8 (100%) 29/30 (97%) through observational cohorts in real time and evidence Bisexual 1/37 (3%) 0/8 1/30 (3%) of infection after vaccination has been reported.18–24 Race and ethnicity More recently, discrete geographical mpox case clusters White 28/37 (76%) 5/8 (63%) 24/30 (80%) have been identified with 55–60% of infections Hispanic or Latinx 4/37 (11%) 3/8 (37%) 1/30 (3%) occurring in people with previous infection or Asian 3/37 (8%) 0/8 3/30 (10%) vaccination.25,26 Complete vaccin­ation with two doses of Black 2/37 (5%) 0/8 2/30 (7%) MVA-BN administered sub­cutaneously or intradermally Sexual partners in the past 30 days 28 days apart was found to have an adjusted vaccine Multiple male partners 32/37 (86%) 6/8 (75%) 27/30 (90%) effectiveness of 86–89% in multiple observational Single male partner 4/37 (11%) 2/8 (25%) 2/30 (7%) cohorts.20,21 Although the duration of vaccine efficacy Multiple male and female partners 1/37 (3%) 0/8 1/30 (3%) remains unclear, these data have noted potentially less Type of sex in the past 30 days severe illness in mpox infection among vaccinated Oral and anal 34/37 (92%) 6/8 (75%) 29/30 (97%) individuals.27 However, these findings have been Anal only 2/37 (5%) 2/8 (25%) 0/30 somewhat contradicted by a large case-control study, Vaginal, oral, and anal 1/37 (3%) 0/8 1/30 (3%) which adjusted for health-seeking behaviour, vaccination Condomless sex in the past 30 days status, and calendar time, showing significantly lower Yes 35/37 (95%) 6/8 (75%) 30/30 (100%) estimated adjusted vaccine effective­ness rates of 35·8% Not known 2/37 (5%) 2/8 (25%) 0/30 after administration of one dose of MVA-BN and Participation in injection drug use for chemsex 66% after two doses.19 No 32/37 (87%) 7/8 (88%) 26/30 (87%) While data around vaccine efficacy are growing, little Yes 3/37 (8%) 1/8 (12%) 2/30 (7%) is known about the demographics and clinical manifest­ Not known 2/37 (5%) 0/8 2/30 (7%) ations of such breakthrough cases. Based on existing HIV status at most recent mpox diagnosis data, we hypothesised that mpox cases after past Negative 29/37 (78%) 3/8 (37%) 27/30 (90%) infection or vaccination, or both, might differ from Positive 8/37 (22%) 5/8 (63%) 3/30 (10%) cases with no past immunity already described in the PrEP use in individuals not living with HIV literature. While WHO declared an end to the PHEIC Yes 24/29 (83%) 3/3 (100%) 22/27 (81%) for mpox in May, 2023, sustained transmission of No 5/29 (17%) 0/3 5/27 (19%) Clade IIb virus has been established in humans, so the CD4 profile of individuals with HIV risk of resurgence remains a real public health threat. CD4 cell count at most recent mpox 555 (363–979) 452 (296–852) 925 (662–1244) Building on the SHARE-Net international clinical diagnosis, cells per mm³ network established at the beginning of the global CD4:CD8 ratio at most recent mpox 0·70 (0·25–1·20) 0·32 (0·25–0·55) 1·05 (0·80–1·53) mpox outbreak, we aim to report on mpox infections in diagnosis a cohort from nine countries after previous infection or CD4 nadir 355 (212–527) 212 (100–300) 527 (435–743) vaccination, and to describe the epidemiology and (Table 1 continues on next page) clinical presentations of these cases. www.thelancet.com/infection Vol 24 January 2024 59  Articles vaccination status or cases with partial immunisation or Total number of Mpox case after Mpox case after individuals* (n=37) past infection (n=8) vaccination (n=30) any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). (Continued from previous page) Last viral load of those with HIV, RNA copies per mL Data collection