Whitni Davidson

Severe Eczema Vaccinatum in a Household Contact of a Smallpox Vaccinee

BACKGROUND We report the first confirmed case of eczema vaccinatum in the United States related to smallpox vaccination since routine vaccination was discontinued in 1972. A 28-month-old child with refractory atopic dermatitis developed eczema vaccinatum after exposure to his father, a member of the US military who had recently received smallpox vaccine. The father had a history of inactive eczema but reportedly reacted normally to the vaccine. The childs mother also developed contact vaccinia infection. METHODS Treatment of the child included vaccinia immune globulin administered intravenously, used for the first time in a pediatric patient; cidofovir, never previously used for human vaccinia infection; and ST-246, an investigational agent being studied for the treatment of orthopoxvirus infection. Serological response to vaccinia virus and viral DNA levels, correlated with clinical events, were utilized to monitor the course of disease and to guide therapy. Burn patient-type management was required, including skin grafts. RESULTS The child was discharged from the hospital after 48 days and has recovered with no apparent systemic sequelae or significant scarring. CONCLUSION This case illustrates the need for careful screening prior to administration of smallpox vaccine and awareness by clinicians of the ongoing vaccination program and the potential risk for severe adverse events related to vaccinia virus.

Spectrum of Infection and Risk Factors for Human Monkeypox, United States, 2003

Infection is associated with proximity to virus-infected animals and their excretions and secretions.

Effective Antiviral Treatment of Systemic Orthopoxvirus Disease: ST-246 Treatment of Prairie Dogs Infected with Monkeypox Virus

ABSTRACT Smallpox preparedness research has led to development of antiviral therapies for treatment of serious orthopoxvirus infections. Monkeypox virus is an emerging, zoonotic orthopoxvirus which can cause severe and transmissible disease in humans, generating concerns for public health. Monkeypox virus infection results in a systemic, febrile-rash illness closely resembling smallpox. Currently, there are no small-molecule antiviral therapeutics approved to treat orthopoxvirus infections of humans. The prairie dog, using monkeypox virus as a challenge virus, has provided a valuable nonhuman animal model in which monkeypox virus infection closely resembles human systemic orthopoxvirus illness. Here, we assess the efficacy of the antiorthopoxvirus compound ST-246 in prairie dogs against a monkeypox virus challenge of 65 times the 50% lethal dose (LD50). Animals were infected intranasally and administered ST-246 for 14 days, beginning on days 0, 3, or after rash onset. Swab and blood samples were collected every 2 days and analyzed for presence of viral DNA by real-time PCR and for viable virus by tissue culture. Seventy-five percent of infected animals that received vehicle alone succumbed to infection. One hundred percent of animals that received ST-246 survived challenge, and animals that received treatment before symptom onset remained largely asymptomatic. Viable virus and viral DNA were undetected or at greatly reduced levels in animals that began treatment on 0 or 3 days postinfection, compared to control animals or animals treated post-rash onset. Animals treated after rash onset manifested illness, but all recovered. Our results indicate that ST-246 can be used therapeutically, following onset of rash illness, to treat systemic orthopoxvirus infections.

Progressive vaccinia: case description and laboratory-guided therapy with vaccinia immune globulin, ST-246 and CMX001

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.

Human Monkeypox Outbreak Caused by Novel Virus Belonging to Congo Basin Clade, Sudan, 2005

TOC Summary: This virus should be considered endemic to the wetland areas of Bentiu, Unity State, Sudan.

Diagnosis of Bovine-Associated Parapoxvirus Infections in Humans: Molecular and Epidemiological Evidence

Orf virus, pseudocowpox virus and bovine papular stomatitis virus, are parapoxviruses, associated with domestic ruminants, which are capable of causing cutaneous infections in humans. Owing to virtually identical appearances in humans, clinical differentiation of these viruses is difficult. We discuss three recent occurrences of parapoxvirus infection, involving contact with domestic bovine and use a combination of molecular and epidemiological data in the diagnosis. These cases underscore the utility of modern diagnostic tools, along with species‐specific contact information in acquiring a definitive diagnosis, in the case of suspected parapoxvirus infection.

Phylogenetic and ecologic perspectives of a monkeypox outbreak, southern Sudan, 2005.

Identification of human monkeypox cases during 2005 in southern Sudan (now South Sudan) raised several questions about the natural history of monkeypox virus (MPXV) in Africa. The outbreak area, characterized by seasonally dry riverine grasslands, is not identified as environmentally suitable for MPXV transmission. We examined possible origins of this outbreak by performing phylogenetic analysis of genome sequences of MPXV isolates from the outbreak in Sudan and from differing localities. We also compared the environmental suitability of study localities for monkeypox transmission. Phylogenetically, the viruses isolated from Sudan outbreak specimens belong to a clade identified in the Congo Basin. This finding, added to the political instability of the area during the time of the outbreak, supports the hypothesis of importation by infected animals or humans entering Sudan from the Congo Basin, and person-to-person transmission of virus, rather than transmission of indigenous virus from infected animals to humans.

Detection and Molecular Characterization of Zoonotic Poxviruses Circulating in the Amazon Region of Colombia, 2014

During 2014, cutaneous lesions were reported in dairy cattle and farmworkers in the Amazon Region of western Colombia. Samples from 6 patients were analyzed by serologic and PCR testing, and results demonstrated the presence of vaccinia virus and pseudocowpox virus. These findings highlight the need for increased poxvirus surveillance in Colombia.

Transmission of Atypical Varicella-Zoster Virus Infections Involving Palm and Sole Manifestations in an Area with Monkeypox Endemicity

During a suspected monkeypox outbreak in the Republic of Congo, we documented transmission of varicella-zoster virus (VZV) infection with palm and sole manifestations among 5 family members. Genotyping results confirmed the VZV strain European E2, a genotype not previously reported in Africa. VZV with palm and sole involvement should be considered when differentiating a monkeypox diagnosis.

Novel Poxvirus in Big Brown Bats, Northwestern United States

A wildlife hospital and rehabilitation center in northwestern United States received several big brown bats with necrosuppurative osteomyelitis in multiple joints. Wing and joint tissues were positive by PCR for poxvirus. Thin-section electron microscopy showed poxvirus particles within A-type inclusions. Phylogenetic comparison supports establishment of a new genus of Poxviridae.