Investigation of an mpox outbreak affecting many vaccinated persons in Chicago, IL-March 2023-June 2023.

BACKGROUND: After months of few mpox cases, an increased number of cases were reported in Chicago during May 2023; predominantly among fully vaccinated patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination. METHODS: We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics, mpox vaccine status, and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered vaccine associated with breakthrough infections. RESULTS: During March 18-June 27, 2023, we identified 49 mpox cases; 57% of these mpox patients were fully vaccinated (FV). FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3, IQR=1-4) versus not fully vaccinated (NFV) patients (1, IQR=1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period. CONCLUSIONS: Our investigation indicated cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

Ecchymotic Plaques on the Scalp of a Man in His 80s.

A man in his 80s had a 4-week history of progressive weakness and fatigue, with associated development of purple bruiselike lesions on his head. What is your diagnosis?

Novel Treatment of a Vaccinia Virus Infection from an Occupational Needlestick - San Diego, California, 2019.

Vaccinia virus (VACV) is an orthopoxvirus used in smallpox vaccines, as a vector for novel cancer treatments, and for experimental vaccine research (1). The Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for laboratory workers who handle replication-competent VACV (1). For bioterrorism preparedness, the U.S. government stockpiles tecovirimat, the first Food and Drug Administration-approved antiviral for treatment of smallpox (caused by variola virus and globally eradicated in 1980*,†) (2). Tecovirimat has activity against other orthopoxviruses and can be administered under a CDC investigational new drug protocol. CDC was notified about an unvaccinated laboratory worker with a needlestick exposure to VACV, who developed a lesion on her left index finger. CDC and partners performed laboratory confirmation, contacted the study sponsor to identify the VACV strain, and provided oversight for the first case of laboratory-acquired VACV treated with tecovirimat plus intravenous vaccinia immunoglobulin (VIGIV). This investigation highlights 1) the misconception among laboratory workers about the virulence of VACV strains; 2) the importance of providing laboratorians with pathogen information and postexposure procedures; and 3) that although tecovirimat can be used to treat VACV infections, its therapeutic benefit remains unclear.

Experimental studies on performance of ventilators stored in the Strategic National Stockpile.

BACKGROUND: The Center for Devices and Radiological Health, Food and Drug Administration (FDA) launched a collaborative initiative with Centers for Disease Control and Prevention (CDC) to gain a better understanding of ventilators that are used during national emergencies. This initiative was intended to test reliability of ventilator devices stored long term in the CDC Strategic National Stockpile (SNS) and also used by the Department of Defense. These ventilators are intended to be used by trained operators to provide ventilatory support to adult and pediatric populations under diverse environmental conditions. The authors evaluated device performance and possible effects of long-term storage. METHODS: Three SNS ventilator models: Impact Uni-Vent 754 Eagle™, Covidien (Puritan Bennett) LP10, and CareFusion LTV 1200 were used in this study. A total of 36 ventilators, 12 per model, were evaluated for performance in simulated adult populations using a test lung. The parameters evaluated included battery charge status and capability, battery longevity, positive end expiratory pressure consistency, device performance on AC and DC (battery) power, and device durability testing. RESULTS: The out-of-the-box run time was equal to or higher than the manufacturer's specifications for fully charged batteries for all ventilators except 58 percent of the Impact 754 ventilators. No significant ventilator performance issues were observed in terms of tidal volume consistency, proximal pressure, oxygen consumption, and a 2000-hour run test in LP10 models. CONCLUSIONS: These findings provide information about the long-term storage of ventilators that have regular maintenance, and their ability to perform reliably during a public health emergency.

Planning Considerations for State, Local, Tribal, and Territorial Partners to Receive Medical Countermeasures From CDC's Strategic National Stockpile During a Public Health Emergency.

The Centers for Disease Control and Prevention's Strategic National Stockpile is a national repository of potentially life-saving medical countermeasures including pharmaceuticals and medical supplies for use in a public health emergency severe enough to cause local, regional, and state supplies to run out. Several planning considerations can assist state, local, tribal, and territorial jurisdictions in preparing to receive, distribute, dispense, and administer medical countermeasures from the Strategic National Stockpile. These considerations include, but are not limited to, issues surrounding regulatory requirements, controlled substances, cold chain management, and ancillary supply needs. Multiple aspects to consider for each of these functions are discussed here to assist partners in their planning efforts.

Polypharmacy and sun exposure: Implications for mitochondrial DNA deletions in skin.

Most somatic cells contain many copies of mitochondrial DNA (mtDNA). Because of both the high copy number and the lack of repair mechanisms available to mtDNA, damage to it largely goes unrepaired, and can accumulate over time. Large scale deletions are a recognised type of damage sustained by mtDNA as a consequence of exposure to the ultraviolet light in sunlight. A group of patients were identified as having abnormally high levels of either a 4977 base pair deletion (mtDNA4977) or 3895 base pair deletion (mtDNA3895), in mtDNA from sun exposed skin or skin suspected to be a non-melanoma skin cancer, but not in their non-sun exposed skin biopsies. In three of the four cases, skin cancer was ruled out due to histological testing. Additional factors from these patients' medical histories were studied, and it was noted that they shared diagnoses for multiple pathologies common to an older population, and that they were being treated with the same or related pharmaceuticals, including some that had been known to cause dermal side effects. Investigation into the biochemistry underlying the symptoms, the effects of sun exposure and side effects of the prescribed pharmaceuticals revealed a possible synergistic relationship leading to the localised high levels of mtDNA deletions.

Case Report of Calciphylaxis Secondary to Calcium and Vitamin D3 Supplementation.

BACKGROUND: Calciphylaxis is a rare disorder that is very unusual outside the setting of end-stage kidney disease. CASE SUMMARY: A 64-year-old woman with normal renal function presented with painful leg ulcers. She had previously received 300 000 IU of vitamin D3 followed by daily calcium and vitamin D3 supplementation. A skin biopsy was consistent with calciphylaxis, and she was treated with sodium thiosulphate infusions and wound debridement. CONCLUSION: Calcium and vitamin D3 supplements are widely prescribed. We report a case of calciphylaxis triggered by calcium and vitamin D3 supplementation in a patient with none of the typical risk factors. Our patient had an excellent response to treatment with sodium thiosulphate.

Mitochondrial DNA deletion percentage in sun exposed and non sun exposed skin.

The percentages of mitochondrial genomes carrying the mtDNA3895 and the mtDNA4977 (common) deletion were quantified in sun exposed and non sun exposed skin biopsies, for five cohorts of patients varying either in sun exposure profile, age or skin cancer status. Non-melanoma skin cancer diagnoses are rising in Ireland and worldwide [12] but most risk prediction is based on subjective visual estimations of sun exposure history. A quantitative objective test for pre-neoplastic markers may result in better adherence to sun protective behaviours. Mitochondrial DNA (mtDNA) is known to be subject to the loss of a significant proportion of specific sections of genetic code due to exposure to ultraviolet light in sunlight. Although one such deletion has been deemed more sensitive, another, called the mtDNA4977 or common deletion, has proved to be a more useful indicator of possible risk in this study. Quantitative molecular analysis was carried out to determine the percentage of genomes carrying the deletion using non sun exposed and sun exposed skin biopsies in cohorts of patients with high or low sun exposure profiles and two high exposure groups undergoing treatment for NMSC. Results indicate that mtDNA deletions correlate to sun exposure; in groups with high sun exposure habits a significant increase in deletion number in exposed over non sun exposed skin occurred. An increase in deletion percentage was also seen in older cohorts compared to the younger group. The mtDNA3895 deletion was detected in small amounts in exposed skin of many patients, the mtDNA4977 common deletion, although present to some extent in non sun exposed skin, is suggested to be the more reliable and easily detected marker. In all cohorts except the younger group with relatively lower sun exposure, the mtDNA4977 deletion was more frequent in sun exposed skin samples compared to non-sun exposed skin.

Artificial White Light vs Daylight Photodynamic Therapy for Actinic Keratoses: A Randomized Clinical Trial.

IMPORTANCE: Daylight photodynamic therapy using topical methyl 5-aminolevulinic acid (MAL) for actinic keratoses (AKs) is as effective as conventional photodynamic therapy but has the advantage of being almost pain free. Daylight photodynamic therapy, however, requires dry and warm weather conditions. OBJECTIVE: To establish if topical MAL photodynamic therapy using a white light light-emitting diode (LED) lamp is as effective and well-tolerated as daylight photodynamic therapy for the treatment of AKs. DESIGN, SETTING, AND PARTICIPANTS: Overall, 22 men with significant photodamage and a high number of AKs were enrolled in this prospective, randomized, single-blind study, employing a split-scalp design, comparing the effectiveness and adverse effects of daylight photodynamic therapy and artificial white light (AWL) LED photodynamic therapy for the treatment of AKs on the forehead and scalp. Organ transplant recipients were excluded. Patients were treated and evaluated at an academic tertiary referral dermatology center. Treatment lasted from April 2014 to July 2014 and follow-up visits occurred for 9 months posttreatment. INTERVENTIONS: Two symmetrical treatment fields were defined and AKs counted, mapped, and photographed at baseline, 1, 3, 6, and 9 months. Patients had half of their scalp treated with daylight photodynamic therapy and the other half treated with AWL photodynamic therapy 1 week apart and randomly allocated. MAL was applied, and treatment commenced 30 minutes later and lasted 2 hours. Irradiance, illuminance, and light spectra measurements were performed. The integrated dose in J/cm2 was measured. The effective light dose, weighted to the absorption spectrum for protoporphyrin IX, was calculated. MAIN OUTCOMES AND MEASURES: The primary end point was the reduction in total AK count per treatment field. Secondary end points included adverse effects and patient satisfaction. RESULTS: We enrolled 22 men with a median age of 72 years (range, 47-85 years) at baseline, the total (median of AKs per field) were 469 (20.5) for the DPDT group and 496 (20.5) for the AWLPDT group (P = .34). The median number and percentage of reduction in AKs per field were 12 and 62.3% for DPDT and 14 and 67.7% for AWLPDT at 1 month (P = .21 and P = .13, respectively). There was no significant difference in the reduction percentage of AKs for either treatment at 1, 3, and 6 months. At 9 months, the median number and percentage of reduction in AKs per field was 9.0 and 48.4% for DPDT and 12.0 and 64.4% for AWLPDT (P = .13 and P = .05, respectively). Pain was reported by 14 patients with DPDT and 16 patients with AWLPDT (median maximum score [out of 100], 4 vs 6; P = .51). Moderate erythema was reported by 9 patients after DPDT and 14 patients after AWLPDT. On a scale of 0 (intolerable) to 10 (very tolerable) patients rated DPDT as 9.5 and AWLPDT as 9 (P = .37). CONCLUSIONS AND RELEVANCE: Photodynamic therapy using an AWL source was as effective and well-tolerated as daylight photodynamic therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02520700.

Contact allergy in cheilitis.

BACKGROUND: Recalcitrant non-actinic cheilitis may indicate contact allergy. OBJECTIVES: This study aimed to determine the prevalence of allergic contact cheilitis (ACC) in patients with non-actinic cheilitis and to identify the most relevant allergens. METHODS: We used an institutional database to identify patients with non-actinic cheilitis who underwent patch testing between January 1, 2001, and August 31, 2011, and conducted a retrospective review of patch test results in these patients. Additional data were obtained from institutional electronic medical records. RESULTS: Ninety-one patients (70 [77%] female; mean age: 51 years) were included in the study. Almost half (41 [45%]) had a final diagnosis of ACC. Patch testing was performed in line with universally accepted methods, with application on day 1, allergen removal and an initial reading on day 3, and the final reading on day 5. The allergens of most significance were fragrance mix, Myroxylon pereirae resin, dodecyl gallate, octyl gallate, and benzoic acid. Nickel was the most relevant metal allergen. CONCLUSIONS: Contact allergy is an important consideration in recalcitrant cheilitis. Fragrances, antioxidants, and preservatives dominated the list of relevant allergens in our patients. Nickel and gold were among the top 10 allergens. Almost half (45%) of these patients had a final diagnosis of ACC. Patch testing beyond the oral complete series should be undertaken in any investigation of non-actinic cheilitis.

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident.

Role of cytokines and chemokines in itch.

Cytokines classically are secreted "messenger" proteins that modulate cellular function of immune cells. Chemokines attract immune cells to the site where they exert various functions in inflammation, autoimmunity or cancer. Increasing evidence is emerging that cytokines or chemokines can act as "neuro-modulators" by activating high-affinity receptors on peripheral or central neurons, microglia cells or Schwann cells. Very recently, cytokines have been shown to act as pruritogens in rodents and humans, while a role of chemokines in itch has thus far been only demonstrated in mice. Upon stimulation, cytokines are released by skin or immune cells and form a "bridge of communication" between the immune and nervous system. For some cytokines such as IL-31 and TSLP, the evidence for this role is strong in rodents. For cytokines such as IL-4, there is some convincing evidence, while for cytokines such as oncostatin M, IL-2, IL-6, IL-8 and IL-13, direct evidence is currently limited. Current clinical trials support the idea that cytokines and chemokines and their receptors or signalling pathways are promising targets for the future therapy of certain subtypes of itch.

Photoaggravated disorders.

Photoaggravated skin disorders are diseases that occur without UV radiation but are sometimes or frequently exacerbated by UV radiation. In conditions, such as lupus erythematosus, photoaggravation occurs in a majority of patients, whereas in conditions, such as psoriasis and atopic dermatitis, only a subset of patients demonstrate photoaggravation. Polymorphous light eruption is a common photodermatosis in all skin types, making it important to differentiate photoaggravation of an underlying disorder, such as lupus erythematosus, from superimposed polymorphous light eruption. Disease-specific treatments should be instituted where possible. A key component of management of photoaggravated conditions is photoprotection with behavioral change, UV-protective clothing, and broad-spectrum sunscreen.

Photosensitizing medications and photocarcinogenesis.

Photosensitivity is an exaggerated or abnormal response to ultraviolet (UV) or visible light exposure. Many current medications are known photosensitizers; however, the effects of the sensitization can be subclinical and go unnoticed by the person affected. While some of these drugs are used for short and defined periods, others are used indefinitely for the treatment of chronic disease. The question of whether either of these practices translates into an increased risk of skin cancer is an important one. Numerous medications have real, distinct and well-elucidated mechanisms that potentiate the development of skin cancer, while with some medications the mechanism for the observed carcinogenesis remains unclear. In this article we will discuss the clinical, mechanistic and epidemiological evidence supporting photochemical genotoxicity and carcinogenesis.