Guidance for the identification of bony lesions related to smallpox.

OBJECTIVE: This research aimed to address the underrepresentation of smallpox (osteomyelitis variolosa) in palaeopathology, providing a synthesis of published literature and presenting guidance for the identification of osteomyelitis variolosa in non-adult and adult skeletal remains. MATERIALS AND METHODS: Literature regarding smallpox and published reports of individuals with osteomyelitis variolosa were synthesised and critiqued to produce clear diagnostic criteria for the identification of smallpox osteologically. RESULTS: Associated osteological changes begin in non-adults, where skeletal morphology is rapidly changing. Characteristic lesions associated with non-adult osteomyelitis variolosa include inflammation and destructive remodelling of long-bone joints and metaphyses. Where childhood infection was survived, residual osteomyelitis variolosa lesions should also be visible in adults in the osteoarchaeological record. CONCLUSIONS: Despite long-term clinical recognition, only limited osteological and archaeological evidence of osteomyelitis variolosa has yet emerged. With improved diagnostic criteria, osteomyelitis variolosa may be more frequently identified. SIGNIFICANCE: This is the first synthesis of osteomyelitis variolosa encompassing both clinical and palaeopathological literature, providing detailed guidance for the identification of osteomyelitis variolosa in skeletal remains. It will lead to the increased identification of smallpox osteologically. LIMITATIONS: Differential diagnoses should always be considered. The archaeological longevity of smallpox, and the potential for archaeological VARV to cause clinically recognised smallpox, is currently unknown. Characteristic bone changes in the archaeological record may be other, extinct human-infecting-orthopoxviruses. SUGGESTIONS FOR FURTHER RESEARCH: Further consideration of the implications of age of smallpox contraction on bony pathology: whether epiphyses are affected differently due to state of fusion. Reassessment of individuals previously identified with smallpox-consistent lesions, but otherwise diagnosed.

Neurologic Complications of Smallpox and Monkeypox: A Review.

Importance: Orthopox viruses include smallpox virus, a once feared but now eradicated virus, as well as monkeypox virus. Monkeypox is an emerging virus initially isolated in 1958, previously unrecognized outside sub-Saharan Africa until a worldwide outbreak in May 2022. It is important to review known neurologic consequences of both these viruses, as complications of smallpox may be relevant to monkeypox, though complications of monkeypox may be rarer and perhaps less severe. Observations: This was a literature review of the known neurologic complications of smallpox, which include encephalitis, transverse myelitis, and acute disseminated encephalomyelitis among others; historical complications of smallpox vaccination, including postvaccinal encephalomyelitis; and the known neurologic complications of monkeypox, which include headaches and mood disturbances, as well as rare presentations of encephalitis, transverse myelitis, and seizures. Of concern is the possibility of viral persistence and systemic complications in immunocompromised individuals. Also provided were considerations for diagnosis, current treatment, and prevention of monkeypox. Conclusions and Relevance: Monkeypox should be considered in high-risk populations who present with neurologic syndromes. Diagnosis may require serology and polymerase chain reaction testing of blood and spinal fluid. Antiviral therapy should be initiated early in the course of the illness.

Myopericarditis Associated With Smallpox Vaccination Among US Army Personnel - Fort Hood, Texas, 2018.

OBJECTIVE: In March 2018, the US Department of Defense (DOD) added the smallpox vaccination, using ACAM2000, to its routine immunizations, increasing the number of persons receiving the vaccine. The following month, Fort Hood reported a cluster of 5 myopericarditis cases. The Centers for Disease Control and Prevention and the DOD launched an investigation. METHODS: The investigation consisted of a review of medical records, establishment of case definitions, causality assessment, patient interviews, and active surveillance. A 2-sided exact rate ratio test was used to compare myopericarditis incidence rates. RESULTS: This investigation identified 4 cases of probable myopericarditis and 1 case of suspected myopericarditis. No alternative etiology was identified as a cause. No additional cases were identified. There was no statistically significant difference in incidence rates between the observed cluster (5.23 per 1000 vaccinated individuals, 95% CI: 1.7-12.2) and the ACAM2000 clinical trial outcomes for symptomatic persons, which was 2.29 per 1000 vaccinated individuals (95% CI: 0.3-8.3). CONCLUSIONS: Vaccination with ACAM2000 is the presumptive cause of this cluster. Caution should be exercised before considering vaccination campaigns for smallpox given the clinical morbidity and costs incurred by a case of myopericarditis. Risk of myopericarditis should be carefully weighed with risk of exposure to smallpox.

Acute Late-Stage Myocarditis in the Crab-Eating Macaque Model of Hemorrhagic Smallpox.

Hemorrhagic smallpox, caused by variola virus (VARV), was a rare but nearly 100% lethal human disease manifestation. Hemorrhagic smallpox is frequently characterized by secondary bacterial infection, coagulopathy, and myocardial and subendocardial hemorrhages. Previous experiments have demonstrated that intravenous (IV) cowpox virus (CPXV) exposure of macaques mimics human hemorrhagic smallpox. The goal of this experiment was to further understand the onset, nature, and severity of cardiac pathology and how it may contribute to disease. The findings support an acute late-stage myocarditis with lymphohistiocytic infiltrates in the CPXV model of hemorrhagic smallpox.

Vitiligo iridis and glaucoma: a rare sequelae of small pox.

PURPOSE: Vitiligo iridis refers to focal areas of iris atrophy as sequelae of small pox infection. We report a series of patients with unilateral vitiligo iridis, some of whom presented with secondary open-angle glaucoma. METHODS: Three patients with vitiligo iridis underwent a comprehensive ophthalmic examination including intraocular pressure (IOP) measurement, slit lamp biomicroscopy, gonioscopy, and fundus evaluation. Patients' facial features were also documented and photographed. RESULTS: All patients were in their sixth decade. Two out the three had elevated IOP (52 mm Hg and 36 mm Hg) in the same eye as vitiligo iridis, at initial presentation. Gonioscopy showed patchy iris hyperpigmentation and fundus evaluation showed glaucomatous optic disc changes in the involved eye. One patient responded favourably to topical antiglaucoma medications, whereas the other was taken up for combined phacoemulsification-trabeculectomy with good results. The third patient had normal IOP in the involved eye. All three patients gave a history of small pox in childhood and had pitted facial scars typical of previous small pox infection. CONCLUSIONS: Vitiligo iridis may be associated with the secondary glaucoma as a long-term sequelae of small pox. It may be prudent to periodically follow-up such patients for development of raised IOP in the future.

Risk of inflammatory bowel disease following Bacille Calmette-Guérin and smallpox vaccination: a population-based Danish case-cohort study.

BACKGROUND: Childhood immunology has been suggested to play a role in development of inflammatory bowel disease (IBD) based on the studies of childhood vaccinations, infections, and treatment with antibiotics. Bacille Calmette-Guérin (BCG) and smallpox vaccinations were gradually phased-out in Denmark for children born between 1965 and 1976, hence allowing the study of subsequent risk of Crohn's disease and ulcerative colitis in a unique prospective design. METHODS: The Copenhagen School Health Records Register contains detailed documentation of vaccination. Among the background cohort of individuals born between 1965 and 1976 (N = 47,622), cases with Crohn's disease (n = 218) and ulcerative colitis (n = 256) were identified through linkage to the Danish National Patient Registry. The vaccination status of the cases was compared with that of a subcohort (n = 5741) of the background cohort and analyzed in a case-cohort design. RESULTS: No difference in risk of IBD was observed between individuals vaccinated and unvaccinated with BCG (hazard ratio = 0.95; 95% confidence interval, 0.75-1.19) or smallpox vaccine (hazard ratio = 1.01; 95% confidence interval, 0.77-1.32). This was also the case for Crohn's disease and ulcerative colitis separately. However, BCG given before 4 months of age may decrease the risk of IBD (hazard ratio = 0.43; 95% confidence interval, 0.20-0.93). CONCLUSIONS: This prospective long-term case-cohort study shows that BCG and smallpox vaccination do not cause IBD later in life. These findings are important for the etiological understanding of IBD and of clinical importance because BCG is still one of the most commonly used childhood vaccinations, smallpox vaccine has been reintroduced in the U.S. military, and both vaccines may be used as vectors in new vaccines.

Sequelae of osteomyelitis variolosa: a case report.

Osteomyelitis variolosa is an osteoarticular complication of small pox infection. We are presenting a case of osteomyelitis variolosa, who presented to us with fracture of ankle on the involved side with other orthopedic sequelae of small pox infection, which he contracted during his childhood period. We have discussed the distinguishing clinical and radiological features of osteomyilitis variolosa.

La viruela y su impacto social: sí o no a la destrucción del virus / No disponible

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Cowpox virus infection of cynomolgus macaques as a model of hemorrhagic smallpox.

Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease within 12 days post-inoculation in two independent experiments. Clinical observations and hematological and histopathological findings support hemorrhagic disease. Cowpox virus replicated to high levels in blood (8.0-9.0 log(10) gene copies/mL) and tissues including lymph nodes, thymus, spleen, bone marrow, and lungs. This unique model of hemorrhagic orthopoxvirus infection provides an accessible means to further study orthopoxvirus pathogenesis and to identify virus-specific and nonspecific therapies. Such studies will serve to complement the existing nonhuman primate models of more classical poxviral disease.

Modification of running Y-V plasty to correct bilateral nostril stenosis with a circular, linear contracture.

Acquired nostril stenosis usually develops from scar contracture due to trauma or infection. The purpose of surgical repair is to emulate the lobule-columella-ala complex, anatomically reconstruct adequate nostrils and maintain long-term patency. A linear scar contracture may be released by a Y-to-V advancement technique, as part of a running Y-V plasty procedure. Nostril stenosis with a circular, linear contracture involving the columella, ala and nostril sill is difficult to correct satisfactorily by W-plasty or Z-plasty alone. We used running Y-V plasty with six triangular flaps of the Y on each external and internal surface in two cases of bilateral nostril stenosis after smallpox, a method that provides one largest external flap for the nostril sill, two external flaps for the ala and the columella each and one external flap for the soft triangle. This technique was easily designed and achieved adequate release and coverage without the use of additional local flaps, and yielded reconstructed nostrils of sufficient size. The running Y-V plasty technique is feasible for correction of nostril stenosis with linear contracture involving the entire nostril rim.

Remaining questions about clinical variola major.

After the recent summary of World Health Organization-authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate.

Osteomyelitis variolosa.

We present a patient with osteomyelitis variolosa in both elbow joints with short middle fingers-sequelae of smallpox. Both elbow joints showed sclerosis of bones around elbow joint, enlargement of olecranon process of ulna, and head of radius with intact joint space. Hands showed shortening of both middle fingers following dactylitis leading to short metacarpals. The purpose of this report is to remind those who seldom see one of the most important and easily recognized complications of smallpox.

[Recovery from blindness following smallpox or measles: Dutch miracle stories, 14th-18th century]. / Genezing van blindheid na pokken of mazelen: Nederlandse mirakelverhalen, 14e-18e eeuw.

Over recent decades, stories of miracles dating from 1380-1726 have been transcribed and are now generally available. These texts only contain a limited amount of medical information. This article closely examines the stories of being cured of blindness after being infected by smallpox or measles. Most of these stories concern children. Eleven of a total of 1700 stories that took place during the above-mentioned period of time concern this type of miracle. The article examines the possible relationship between these miracles and a lack of vitamin A.

Osteomyelitis variolosa: a report of two cases.

We present 2 patients with osteomyelitis variolosa in both elbow joints--sequelae of smallpox. The condyles were elongated and the central portions of the distal humeri were absorbed and the elbow joints were unstable. One of the patients sustained a closed fracture of the distal humerus. The fracture united uneventfully following stabilisation and bone grafting. At the 13-year follow-up, the patient had satisfactory elbow function.