The changing epidemiology of human monkeypox - a potential threat? A systematic review

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010-2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades - Central African 10.6% (95% CI: 8.4% - 13.3%) vs. West African 3.6% (95% CI: 1.7% - 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

553 Myocarditis after COVID-19 vaccination—a case series

Myocarditis has been recognized as a rare complication of SARS-CoV-2 infection even in the absence of lung involvement and recent histological findings suggest that COVID-19-related myocardial damage may differ from other typical lymphocytic myocarditis associated with other viruses and could be possibly linked to diffuse infiltration of monocytes and macrophage leading to microvascular dysfunction and cell necrosis. SARS-CoV-2 vaccines have been well tolerated and associated with decreasing burden of disease in areas with high vaccination rates. Minor side-effects have been frequently described, mainly after second dose. Here, we report our findings in four male patients consistent with acute myocarditis at our Institutional Hospital; all four had recently received a second-dose mRNA vaccine. All presented with acute chest pain associated with biomarker evidence of myocardial injury and were hospitalized. None of them had a previous history of SARS-CoV2 infection. All of them showed markedly abnormal EKG findings with diffuse ST segment elevation and laboratory tests revealed elevated high-sensitivity (hs) troponin T levels and C-reactive protein with no peripheral eosinophilia. All patients underwent nasopharyngeal swabbing and the specimens were tested for common respiratory viruses by RT-PCR and resulted all negative. All patients underwent CMR scan during hospitalization. The hospital course was benign for all patients without evidence of arrhythmias or heart failure, in all cases we performed a conservative treatment with nonsteroidal anti-inflammatory drugs and colchicine with progressive normalization of troponin levels before discharge. Our cases presented features of acute myocarditis with a temporal association with the mRNA Covid-19 vaccination, in absence of other apparent causes (in fact none had viral prodromes) nor COVID-19 infection in the prior year. Several reports in the past months had suggested a possible association between the mRNA Covid-19 and myocarditis, most of the cases presenting in young males, after the second dose and with a favourable course. Thus, given the potential risk of cardiac involvement after SARS-CoV-2 infection even in younger adults, the risk-benefit decisions favours vaccination for population immunity. Despite this, the potential mechanisms of SARS-CoV-2 vaccine-related myocarditis seem different from the previously described eosinophilic myocarditis after smallpox vaccination remain unclear and vaccine adverse event reporting remains of high importance. Figure 1 shows one acute MRI scan with STIR, T2-map and LGE in short-axis and apical four-chamber view.

Vaccinia Virus: From Crude Smallpox Vaccines to Elaborate Viral Vector Vaccine Design

Various vaccinia virus (VACV) strains were applied during the smallpox vaccination campaign to eradicate the variola virus worldwide. After the eradication of smallpox, VACV gained popularity as a viral vector thanks to increasing innovations in genetic engineering and vaccine technology. Some VACV strains have been extensively used to develop vaccine candidates against various diseases. Modified vaccinia virus Ankara (MVA) is a VACV vaccine strain that offers several advantages for the development of recombinant vaccine candidates. In addition to various host-restriction genes, MVA lacks several immunomodulatory genes of which some have proven to be quite efficient in skewing the immune response in an unfavorable way to control infection in the host. Studies to manipulate these genes aim to optimize the immunogenicity and safety of MVA-based viral vector vaccine candidates. Here we summarize the history and further work with VACV as a vaccine and present in detail the genetic manipulations within the MVA genome to improve its immunogenicity and safety as a viral vector vaccine.

Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and enhance immunity

Interactions between pathogens, host microbiota and the immune system influence many physiological and pathological processes. In the 20 th century, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox but how VACV interacts with the microbiota and whether this influences the efficacy of vaccination are largely unknown. Here we report that intradermal vaccination with VACV induces a large increase in the number of commensal bacteria in infected tissue, which enhance recruitment of inflammatory cells, promote tissue damage and increase immunity. Treatment of vaccinated specific-pathogen-free (SPF) mice with antibiotic, or infection of genetically-matched germ-free (GF) animals caused smaller lesions without alteration in virus titre. Tissue damage correlated with enhanced neutrophil and T cell infiltration and levels of pro-inflammatory tissue cytokines and chemokines. One month after vaccination, GF mice had reduced VACV-neutralising antibodies compared to SPF mice; while numbers of VACV-specific CD8 + T cells were equal in all groups of animals. Thus, skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV. This observation has implications for dermal vaccination with live vaccines.

War of conscience: antivaccination and the battle for medical freedom during World War I

The nineteenth century British antivaccination movement attracted popular and parliamentary support and ultimately saw the 1853 law which had made smallpox vaccination compulsory nullified by the 1898 ‘conscientious objector’ clause. In keeping with popular public health discourse of the time, the movement had employed rhetoric associated with sanitary science and liberalism. In the early twentieth century new discoveries in bacteriology were fuelling advances in vaccination and the medical establishment was increasingly pushing for public health to move towards more interventionist medical approaches. With the onset of war in 1914, the medical establishment hoped to persuade the government to introduce compulsory typhoid inoculation for soldiers. This article analyses antivaccination literature, mainstream newspapers and medical press along with parliamentary debates to examine how the British antivaccination movement engaged with this new threat of compulsion by expanding the rhetoric of ‘conscience’ and emphasising medical freedom while also asserting scientific critique concerning the effectiveness of vaccines and the new laboratory based diagnostic practices. In spite of ‘conscience’ fitting well with an emerging public health discourse of individual subjectivity, the mainstream press ridiculed the idea of working-class soldiers having a conscience, coalescing around the idea that ‘conscientious objection’ be reserved for spiritual, philosophical and educated men who objected to military service. Moreover, in spite of engaging in reasoned scientific critique, parliament and press consorted in the demarcation of scientific knowledge as exclusive to medical scientists, reflecting a growing allegiance between the state and the medical establishment during the war. Any scientific arguments critical of medical orthodoxy were subjugated, labelled as ‘crank’ or ‘faddist’ as well as unpatriotic. The antivaccination narratives around conscience contributed to or were part of an evolving discourse on consent and ethics in medicine. Potential parallels are drawn with current and likely future debates around vaccination and counterhegemonic scientific approaches.