A compilation answering 50 questions on monkeypox virus and the current monkeypox outbreak.

The current monkeypox disease (MPX) outbreak constitutes a new threat and challenge for our society. With more than 55,000 confirmed cases in 103 countries, World Health Organization declared the ongoing MPX outbreak a Public Health Emergency of International Concern (PHEIC) on July 23, 2022. The current MPX outbreak is the largest, most widespread, and most serious since the diagnosis of the first case of MPX in 1970 in the Democratic Republic of the Congo (DRC), a country where MPX is an endemic disease. Throughout history, there have only been sporadic and self-limiting outbreaks of MPX outside Africa, with a total of 58 cases described from 2003 to 2021. This figure contrasts with the current outbreak of 2022, in which more than 55,000 cases have been confirmed in just 4 months. MPX is, in most cases, self-limiting; however, severe clinical manifestations and complications have been reported. Complications are usually related to the extent of virus exposure and patient health status, generally affecting children, pregnant women, and immunocompromised patients. The expansive nature of the current outbreak leaves many questions that the scientific community should investigate and answer in order to understand this phenomenon better and prevent new threats in the future. In this review, 50 questions regarding monkeypox virus (MPXV) and the current MPX outbreak were answered in order to provide the most updated scientific information and to explore the potential causes and consequences of this new health threat.

Monkeypox outbreak in Spain: clinical and epidemiological findings in a prospective cross-sectional study of 185 cases.

BACKGROUND: Since May 2022, a new outbreak of monkeypox has been reported in several countries, including Spain. The clinical and epidemiological characteristics of the cases in this outbreak may differ from those in earlier reports. OBJECTIVES: To document the clinical and epidemiological characteristics of cases of monkeypox in the current outbreak. METHODS: We conducted a prospective cross-sectional study in multiple medical facilities in Spain to describe the cases of monkeypox in the 2022 outbreak. RESULTS: In total, 185 patients were included. Most cases started with primarily localized homogeneous papules, not pustules, in the probable area of inoculation, which could be cutaneous or mucous, including single lesions. Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common lesions included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Four patients were hospitalized, none died. Smallpox vaccination and well-controlled HIV disease were not associated with markers of severity. Contact during sex is the most likely mechanism of transmission. In this outbreak, cases have been described in men who have sex with men and are strongly associated with high-risk sexual behaviours. Seventy-six per cent of the patients had other sexually transmitted diseases upon screening. CONCLUSIONS: The clinical findings in this outbreak differ from previous findings and highly suggest contact transmission and initiation at the entry site. The characterization of the epidemiology of this outbreak has implications for control. What is already known about this topic? Monkeypox eruption is described as consisting of pustules. The roles of HIV and previous smallpox vaccination in the prognosis are unknown. The transmission route was initially described as respiratory droplets and was later suggested to be via sexual contact. What does this study add? Initial lesions at the probable inoculation area were homogeneous and papular (pseudopustules). Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common signs included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Well-controlled HIV and previous smallpox vaccination were not associated with severity. No patient died. The data support the hypothesis of transmission via contact during sex. Although this might change, the outbreak is currently limited mostly to men who have sex with men, with high-risk factors for sexually transmitted diseases.

Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022.

A monkeypox (MPX) outbreak has expanded worldwide since May 2022. We tested 147 clinical samples collected at different time points from 12 patients by real-time PCR. MPX DNA was detected in saliva from all cases, sometimes with high viral loads. Other samples were frequently positive: rectal swab (11/12 cases), nasopharyngeal swab (10/12 cases), semen (7/9 cases), urine (9/12 cases) and faeces (8/12 cases). These results improve knowledge on virus shedding and the possible role of bodily fluids in disease transmission.

First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain.

Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.

SARS-CoV-2, COVID-19, skin and immunology - What do we know so far?

The pandemic condition coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2-positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial, and maculopapular eruptions and livedo, necrosis, and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors, and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical, and histologic features of virus- and drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.

Maculopapular eruptions associated to COVID-19: A subanalysis of the COVID-Piel study.

A previous study has defined the maculopapular subtype of manifestations of COVID-19. The objective of our study was to describe and classify maculopapular eruptions associated with COVI-19. We carried out a subanalysis of the maculopapular cases found in the previous cross-sectional study. Using a consensus, we defined seven clinical patterns. We described patient demographics, the therapy received by the patient and the characteristics of each pattern. Consensus lead to the description of seven major maculopapular patterns: morbilliform (45.5%), other maculopapular (20.0%), purpuric (14.2%), erythema multiforme-like (9.7%), pytiriasis rosea-like (5.7%), erythema elevatum diutinum-like (2.3%), and perifollicular (2.3%). In most cases, maculopapular eruptions were coincident (61.9%) or subsequent (34.1%) to the onset of other COVID-19 manifestations. The most frequent were cough (76%), dyspnea (72%), fever (88%), and astenia (62%). Hospital admission due to pneumonia was frequent (61%). Drug intake was frequent (78%). Laboratory alterations associated with maculo-papular eruptions were high C-reactive protein, high D-Dimer, lymphopenia, high ferritin, high LDH, and high IL-6. The main limitation of our study was the impossibility to define the cause-effect relationship of each pattern. In conclusion, we provide a description of the cutaneous maculopapular manifestations associated with COVID-19. The cutaneous manifestations of COVID-19 are wide-ranging and can mimic other dermatoses.

Changing plasma cytokine, chemokine and growth factor profiles upon differing malaria transmission intensities.

BACKGROUND: Malaria epidemiological and immunological data suggest that parasite tolerance wanes in the absence of continuous exposure to the parasite, potentially enhancing pathogenesis. The expansion of control interventions and elimination campaigns raises the necessity to better understand the host factors leading to susceptibility or tolerance that are affected by rapid changes in malaria transmission intensity (MTI). Mediators of cellular immune responses are responsible for the symptoms and pathological alterations during disease and are expected to change rapidly upon malaria exposure or cessation. METHODS: The plasma concentrations of 30 cytokine, chemokine and growth factors in individuals of all ages from a malaria endemic area of southern Mozambique were compared between 2 years of different MTI: 2010 (lower, n = 234) and 2013 (higher, n = 143). The effect of the year on the correlations between cytokines, chemokines and growth factors and IgGs to Plasmodium falciparum (markers of exposure) was explored. The effects of age, sex, neighbourhood and parasitaemia on analyte levels and their interactions with year were also assessed. RESULTS: An inverse correlation of several cellular immune mediators with malarial antibodies in 2013, and a lack of correlation or even a positive correlation in 2010 were observed. Most cytokines, chemokines and growth factors, regardless of their immune function, had higher concentrations in 2010 compared with 2013 in P. falciparum-infected and uninfected subjects. Age and neighbourhood showed an effect on analyte concentrations. CONCLUSIONS: The results show a different regulation of the cellular immune response in 2010 vs 2013 which could be related to a loss of immune-tolerance after a decline in MTI in 2010 and previous years, and a rapid re-establishment of tolerance as a consequence of more continuous exposure as MTI began increasing in 2012. Cellular immune mediators warrant further investigation as possible surrogates of MTI-associated host susceptibility or tolerance.

Patients With Systemic Lupus Erythematosus Show an Increased Arterial Stiffness That is Predicted by IgM Anti-ß2 -Glycoprotein I and Small Dense High-Density Lipoprotein Particles.

OBJECTIVE: To investigate the metabolic and immunologic factors associated with the presence of central arterial stiffness as measured by the augmentation index (AIx). METHODS: We conducted a cross-sectional study of 69 female patients with systemic lupus erythematosus (SLE) compared with a control group of 34 healthy women. The anthropometrical variables, the vascular studies, and the analytic data were obtained the same day. The AIx was assessed by peripheral arterial tonometry. The analysis of lipoprotein populations was performed using nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Arterial stiffness was increased in patients with SLE compared with control subjects (mean ± SD 20.30 ± 21.54% versus 10.84 ± 11.51%; P = 0.0021). Values for the AIx were correlated with the Framingham risk score (r = 0.481, P < 0.001), carotid intima-media thickness (r = 0.503, P < 0.001), systolic blood pressure (r = 0.270, P < 0.001), and age (r = 0.365, P < 0.001). Patients receiving antimalarial drugs had a lower AIx (mean ± SD 11.74 ± 11.28% versus 24.97 ± 20.63%; P = 0.024). The AIx was correlated with the atherogenic lipoproteins analyzed by NMR. The immunologic variables associated with the AIx were C4 (r = 0.259, P = 0.046) and IgM anti-ß2 -glycoprotein I (IgM anti-ß2 GPI) (r = 0.284, P = 0.284). In the multivariate analysis, age (ß = 0.347, 95% confidence interval [95% CI] 0.020-0.669, P = 0.035), IgM ß2 GPI (ß = 0.321, 95% CI 0.024-0.618, P = 0.035) and small dense high-density lipoprotein (HDL) particles (ß = 1.288, 95% CI 0.246-2.329, P = 0.017) predicted the AIx. CONCLUSION: SLE patients had increased arterial stiffness compared with healthy control subjects. Arterial stiffness was decreased in patients treated with antimalarial drugs. Age, IgM ß2 GPI, and the number of small dense HDL particles predicted the AIx.

Anti-tumour necrosis factor-induced visceral and cutaneous leishmaniasis: case report and review of the literature.

BACKGROUND: Leishmaniasis is a chronic protozoan disease in which organisms are found within phagolysosomes of the mononuclear phagocyte system. There are three major forms: cutaneous, mucocutaneous and visceral. We report the first case of visceral leishmaniasis with cutaneous involvement in a patient with rheumatoid arthritis treated with the anti-tumour necrosis factor (anti-TNF) adalimumab. OBJECTIVE: To highlight cutaneous leishmaniasis as the first indicator of a kala-azar disease in a patient treated with anti-TNF and to review the literature on leishmaniasis in the context of anti-TNF therapy. CASE REPORT: A 59-year-old woman presented with a crusted plaque on the right elbow 34 months after the initiation of adalimumab. A cutaneous biopsy showed intracellular amastigotes. No Leishmania parasites were observed in a bone marrow aspirate, but laboratory tests showed anaemia and impaired liver function, abdominal ultrasonography showed hepatomegaly, and ELISA serology was strongly positive for Leishmania antibodies in serum and urine. Adalimumab was withdrawn and treatment combining intralesional pentavalent antimonials and liposomal amphotericin was started. Eight weeks later, the leishmaniasis had resolved. CONCLUSION: A skin biopsy disclosing leishmaniasis should prompt tests to rule out visceral leishmaniasis, especially in an area such as the Mediterranean where the prevalence of latent Leishmania infection is high.

Acute severe methotrexate toxicity in patients with psoriasis: a case series and discussion.

BACKGROUND: Methotrexate (MTX) is considered a relatively safe drug when prescribed at low-dose regimens not exceeding 25 mg/week. Severe acute toxicity is rare and presents with mucositis, cutaneous ulceration and pancytopenia. Most cases occur as the result of inadvertent overdosing due to erroneously taking the drug daily. However, concomitant factors such as older age, co-medication and renal failure may increase the drug's toxicity. CASE REPORTS: We report four consecutive cases of acute MTX toxicity in patients with psoriasis vulgaris. In three patients, MTX was erroneously taken daily for 2-4 weeks. All three patients recovered following MTX withdrawal and intensive treatment. The fourth patient was taking 7.5 mg weekly MTX as prescribed, but had concomitant factors and died. CONCLUSION: Although low-dose MTX appears to be a safe medication, acute MTX toxicity can be a life-threatening emergency. Greater awareness of possible MTX toxicity is still needed for its prevention, early diagnosis and management.

Una Experiencia de Investigación, Formación e Intervención con Hombres Penados por Violencia contra la Mujer en la Universidad de Valencia: Programa Contexto / A Research, Training and Intervention Experience at University of Valencia with Men Convicted of Violence Against Women: Programa Contexto

Resumen. En España, a partir de la entrada en vigor de la Ley Orgánica 1/2004 de Medidas de Protección Integral contra la Violencia de Género, los programas de intervención para maltratadores se han convertido en un recurso necesario para el cumplimiento de las suspensiones de condena condicionadas, en casos de violencia de género. El objetivo de este artículo es presentar el trabajo realizado desde el Programa Contexto (Universidad de Valencia) en el ámbito de la investigación, formación e intervención con penados por violencia de género. En primer lugar, se describen las principales características y líneas directrices de la intervención en el Programa junto con la estructura y fases de la misma. En segundo lugar, se detalla el proceso de formación establecido para los colaboradores en el programa y las actividades de formación desarrolladas por parte de los miembros del equipo. Por último, se presentan las principales líneas de investigación que están orientando el trabajo del equipo que forma parte del Programa Contexto, así como algunos resultados preliminares (AU)

Abstract. In Spain, after the coming into force of Organic Law 1/2004 (Integral Protection Measures against Gender Violence) intervention programs for perpetrators of domestic violence have become necessary for the application of conditional suspended sentences in cases of gender violence. The aim of this paper is to present the work done in the Programa Contexto (University of Valencia) in the field of research, training and intervention in those convicted of domestic violence. Firstly, we describe the main characteristics and guidelines for intervention in the program, in conjunction with its structure and different phases. Secondly, the training process provided for volunteers on the program is described, and the training activities developed by the team members. Finally, we present the main lines of research that are guiding the work of the team that is part of Programa Contexto and the preliminary results (AU)