In August 2022, in response to a global mpox outbreak, the World Health Organization recommended the Vaccinia vaccination for at-risk people.
Case study.
We describe a case of a HIV-negative bisexual man who developed a symptomatic mpox infection 13weeks after completing a two-dose course of subcutaneous third-generation modified vaccinia Ankara vaccines. The case likely acquired his mpox infection in the USA; was diagnosed in Aotearoa, New Zealand; and was followed-up in Australia, as he was actively travelling during his infection.
This case highlights the importance of maintaining clinical suspicion for mpox in people who present with consistent symptoms, even if they are fully vaccinated. Also, as he travelled around Aotearoa, New Zealand, and Australia during his infection, this case highlights how public health authorities and clinicians can cooperate across jurisdictional boundaries to support cases and minimise the risk of onward transmission.

BACKGROUND The emergence of the monkeypox virus (mpox) is causing a large-scale re-administration of vaccinia-based vaccines. Many physicians have not been exposed to the rare, but implicit, complications, revealing a glaring need for updated evidence and re-examination. We present a case of a Human Immunodeficiency Virus (HIV)-positive male patient who presented to the Emergency Department (ED) with vaccinia symptoms several days after receiving the JYNNEOS vaccine. CASE REPORT A 45-year-old man with a past medical history of well-controlled HIV presented to the ED for 5 days of nocturnal diaphoresis, chills, intermittent arthralgia, and myalgia that began shortly after receiving the JYNNEOS vaccine. The patient reported an intermittent fever of 101°F (38.3°C) but denied cough, chest pain, and dyspnea, and had otherwise normal vital signs. Serum lab test results were significant for elevated leukocytosis of 13.4 and CRP of 7.0, but were otherwise normal. The patient reported complete resolution of his symptoms after a 14-day follow-up via phone call. CONCLUSIONS Mpox is unfortunately spreading across the globe; therefore, many treatments and vaccines are being studied to address the outbreak. The latest generation of vaccines employ an attenuated vaccinia virus and are separated into replicating and non-replicating categories, and while generally safer than previous variola vaccines, they still are associated with rare complications and adverse effects. Generally, vaccinia symptoms are mild and self-resolving. Treatment is largely supportive and most patients can be discharged following general serum lab work-up and cardiopulmonary assessment.

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Camelpox virus is the causative agent of Camelpox, a highly contagious disease of camels. A high passage Camelpox virus strain has previously been reported to contain several genes which more closely resemble Vaccinia, a virus species with no known natural host, encompassing various strains that show high inter-strain genomic variation. In this study, we demonstrate that yet another high passage, live attenuated vaccine, comprising a different strain of Camelpox virus, contains genomic sequences that match a differing strain of Vaccinia virus. These results are discussed in the context of hypotheses put forward to explain the unknown origins of Vaccinia virus, suggesting further studies to elucidate evolutionary trajectories of Orthopoxviruses through passaging.

Emerging and understudied pathogens often lack information that most commonly used analytical tools require, such as negative controls or baseline data; thus, new analytical strategies are needed to analyze transmission patterns and drivers of disease emergence. Zoonotic infections with Vaccinia virus (VACV) were first reported in Brazil in 1999, VACV is an emerging zoonotic Orthopoxvirus, which primarily infects dairy cattle and farmers in close contact with infected cows. Prospective studies of emerging pathogens could provide critical data that would inform public health planning and response to outbreaks. By using the location of 87-recorded outbreaks and publicly available bioclimatic data, we demonstrate one such approach. Using an ecological niche model (ENM) algorithm, we identify the environmental conditions under which VACV outbreaks have occurred, and determine additional locations in two affected countries that may be susceptible to transmission. Further, we show how suitability for the virus responds to different levels of various environmental factors and highlight the most important factors in determining its transmission.
A literature review was performed and the geospatial coordinates of 87 molecularly confirmed VACV outbreaks in Brazil were identified. An ENM was generated using MaxENT software by combining principal component analysis results of 19 bioclim spatial layers, and 25 randomly selected subsets of the original list of 87 outbreaks.
The final ENM predicted all areas where Brazilian outbreaks occurred, one out of five of the Colombian outbreak regions and identified new regions within Brazil that are suitable for transmission based on bioclimatic factors. Further, the most important factors in determining transmission suitability are precipitation of the wettest quarter, annual precipitation, mean temperature of the coldest quarter and mean diurnal range.
The analyses here provide a means by which to study patterns of an emerging infectious disease and identify regions that are potentially suitable for its transmission, in spite of the paucity of high-quality critical data. Policy and methods for the control of infectious diseases often use a reactionary model, addressing diseases only after significant impact on human health has ensued. The methodology used in the present work allows the identification of areas where disease is likely to appear, which could be used for directed intervention.

When vaccinations with vaccinia against smallpox and Bacillus Calmette-Guérin (BCG) against tuberculosis were phased out in some high-income countries around 1980, the impact on overall mortality was not examined. Recent studies from low-income countries have suggested that these vaccines are associated with mortality reductions, not explained by specific disease protection. We examined whether vaccinia and BCG administered in childhood were associated with long-term mortality reductions in a high-income population.
In this case-cohort study, we followed 47 622 schoolchildren from Copenhagen, Denmark, born 1965 to 1976, from their first health examination to 2010. This cohort experienced the phase-out of vaccinia and BCG vaccination programmes.
A sub-cohort of 5 316 individuals (699 excluded) was followed for 164 450 person-years (0.2% were lost to follow-up), and 401 deaths due to natural causes (841 deaths in total) occurred in the full cohort. Compared with individuals who had not received vaccinia or BCG, those who had received both vaccinia and BCG had an adjusted hazard ratio (aHR) of 0.54 [95% confidence interval (CI): 0.36-0.81] for mortality due to natural causes of death; those who only received BCG had an aHR of 0.58 (95% CI: 0.39-0.85). Vaccinia and BCG were not associated with any protection against deaths by accidents, suicide or murder, the combined aHR being 0.94 (95% CI: 0.62-1.42).
Vaccinia and BCG vaccinations were associated with better long-term survival, which was not explained by specific protection. Vaccines with beneficial non-specific effects may reduce overall mortality even after the target diseases are eradicated.

Vaccinia virus (VACV), the etiological agent of an exanthematic disease, has been associated with several bovine outbreaks in Brazil since the end of the global vaccination campaign against smallpox. It was previously believed that the vaccine virus used for the WHO global campaign had adapted to an unknown wild reservoir and was sporadically re-emerging in outbreaks in cattle and milkers. At present, it is known that Brazilian VACV is phylogenetically different from the vaccinia virus vaccinal strain, but its origin remains unknown. This study assessed the seroprevalence of orthopoxviruses in domestic and wild animals and farmers from 47 farms in three cities in the southwest region of the state of São Paulo with or without official reports of outbreaks in cattle or humans. Our data indicate a low seroprevalence of antibodies in wild animals and raise interesting questions about the real potential of wild rodents and marsupials as VACV reservoirs, suggesting other routes through which VACV can be spread.

Progressive vaccinia (PV) is a rare but potentially lethal complication that develops in smallpox vaccine recipients with severely impaired cellular immunity. We describe a patient with PV who required treatment with vaccinia immune globulin and who received 2 investigational agents, ST-246 and CMX001. We describe the various molecular, pharmacokinetic, and immunologic studies that provided guidance to escalate and then successfully discontinue therapy. Despite development of resistance to ST-246 during treatment, the patient had resolution of PV. This case demonstrates the need for continued development of novel anti-orthopoxvirus pharmaceuticals and the importance of both intensive and timely clinical and laboratory support in management of PV.

Vaccinia virus is responsible for a zoonosis that usually affects cattle and human beings in Brazil. The initial clinical signs of the infection are focal red skin areas, fever, and general symptoms similar to those of a cold. Then, pustules and ulcerated lesions surrounded by edema and erythema follow, as well as local lymphadenopathy that can last for weeks. Cure and healing of the lesions occur over several weeks, leaving a typical scar in the skin of people and animals affected. The infection definitive diagnosis is made through morphological characterization of the virus by use of electron microscopy, followed by PCR for specific viral genes. Since 1963, circulating orthopoxviruses in infectious outbreaks in several regions of Brazil have been reported. Later, the etiological agent of those infections was characterized as samples of Vaccinia virus. In addition, the widespread use of those viruses in research laboratories and mass vaccination of militaries have contributed to increase the cases of those infections worldwide. Thus, several epidemiological and clinical studies are required, as well as studies of viral immunology, public health, and economic impact, because little is known about those Vaccinia virus outbreaks in Brazil.

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