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BACKGROUND: The COVID-19 pandemic put healthcare professionals, including residents (postgraduate trainees of health professions), under intense physical and psychological stress, hence at risk for mental disorders. We evaluated the prevalence of mental disorders among healthcare residents during the pandemic. METHODS: From July to September 2020, residents in medicine and other healthcare specialties in Brazil were recruited. The participants completed electronic forms with validated questionnaires (DASS-21, PHQ-9, BRCS) to screen for depression, anxiety, and stress, and to evaluate resilience. Data on potential predisposing factors for mental disorders were also collected. Descriptive statistics, chi-squared, students t, correlation and logistic regression models were applied. The study received ethical approval, and all participants provided informed consent. RESULTS: We included 1313 participants (51.3% medical; 48.7% nonmedical) from 135 Brazilian hospitals; mean (SD) age: 27.8 (4.4) years; 78.2% females; 59.3% white race. Of all participants, 51.3%, 53.4% and 52.6% presented symptoms consistent with depression, anxiety, and stress, respectively; 61.9% showed low resilience. Nonmedical residents exhibited higher anxiety compared to medical residents (DASS-21 anxiety score, mean difference: 2.26; 95% CI: 1.15-3.37; p < 0.001). In multivariate analyses, having any pre-existent, nonpsychiatric chronic disease was associated with higher prevalence of symptoms indicative of depression (odds ratio, OR: 2.05; 95% CI: 1.47-2.85, on DASS-21 | OR: 2.26; 95% CI: 1.59-3.20, on PHQ-9), anxiety (OR: 2.07; 95% CI: 1.51-2.83, on DASS-21), and stress (OR: 1.53; 95% CI: 1.12-2.09, on DASS-21); other predisposing factors were identified; by contrast, high resilience (BRCS score) was protective against symptoms of depression (OR 0.82; 95% CI: 0.79-0.85, on DASS-21 | OR 0.85; 95% CI: 0.82-0.88, on PHQ-9), anxiety (OR 0.90; 95% CI: 0.87-0.93, on DASS-21), and stress (OR 0.88; 95% CI: 0.85-0.91, on DASS-21); p < 0.05 for all outcomes. CONCLUSIONS: We found a high prevalence of mental disorder symptoms among healthcare residents during COVID-19 pandemic in Brazil. Nonmedical residents exhibited higher levels of anxiety than medical ones. Some predisposing factors for depression, anxiety and stress among residents were identified.
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COVID-19 , Trastornos Mentales , Femenino , Humanos , Adulto , Masculino , COVID-19/epidemiología , Pandemias , Prevalencia , SARS-CoV-2 , Depresión/diagnóstico , Salud Mental , Ansiedad/psicologíaRESUMEN
The Aedes aegypti mosquito significantly impacts public health, with vector control remaining the most efficient means of reducing the number of arboviral disease cases. This study screened the larvicidal and pupicidal activity of common edible plant extracts. Piper nigrum L. (black pepper) extract production was optimized using accelerated solvent extraction (ASE) and validated following regulatory requirements using HPLC-PDA analytical methodology to quantify its major component-piperine. Larvicidal activity was determined for the standardized P. nigrum fruit ethanol extract (LC50 1.1 µg/mL) and piperine standard (LC50 19.0 µg/mL). Furthermore, 9-day residual activity was determined for the extract (4 µg/mL) and piperine (60 µg/mL), with daily piperine quantification. Semi-field trials of solid extract formulations demonstrated 24-day activity against Ae. aegypti larvae. Thus, the standardized P. nigrum extract emerges as a potential candidate for insecticide development to control the arboviral vector.
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Aedes , Insecticidas , Piper nigrum , Animales , Insecticidas/farmacología , Extractos Vegetales/farmacología , Mosquitos Vectores , Larva , Hojas de la PlantaRESUMEN
Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone (folP1), rifampin (rpoB), and ofloxacin resistance (gyrA) was performed. During the referral period, 63,520 active leprosy patients were registered in Brazil, and 1,183 fulfilled the inclusion criteria for molecular AMR investigation. In total, only 16 (1.4%) patients had genetic polymorphisms associated with AMR. Of these, 8 (50%) had cases of leprosy relapse, 7 (43.8%) had cases of suspected therapeutic failure with standard treatment, and 1 (6.2%) was a case of new leprosy presentation. M. leprae strains with AMR-associated mutations were found for all three genes screened. Isolates from two patients showed simultaneous resistance to dapsone and rifampin, indicating multidrug resistance (MDR). No significant relationship between clinical variables and the presence of AMR was identified. Our study revealed a low frequency of AMR in Brazil. Isolates were resistant mainly to dapsone, and a very low number of isolates were resistant to rifampin, the main bactericidal agent for leprosy, or presented MDR, reinforcing the importance of the standard World Health Organization multidrug therapy. The greater frequency of AMR among relapsed patients supports the need to constantly monitor this group.
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Leprostáticos , Lepra , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Brasil/epidemiología , Estudios Transversales , Dapsona/uso terapéutico , Farmacorresistencia Bacteriana/genética , Quimioterapia Combinada , Humanos , Leprostáticos/farmacología , Leprostáticos/uso terapéutico , Lepra/tratamiento farmacológico , Lepra/epidemiología , Lepra/microbiología , Pruebas de Sensibilidad Microbiana , Mycobacterium leprae/genética , Recurrencia , Rifampin/farmacología , Rifampin/uso terapéuticoRESUMEN
BACKGROUND: Recently developed immunosuppressive drugs, especially TNF antagonists, may enhance the risk of granulomatous infections, including leprosy. We aimed to evaluate the leprosy detection rate in patients under immunosuppression due to rheumatological, dermatological and gastroenterological diseases. METHODS: We performed a systematic review of the literature by searching the PubMed, EMBASE, LILACS, Web of Science and Scielo databases through 2018. No date or language restrictions were applied. We included all articles that reported the occurrence of leprosy in patients under medication-induced immunosuppression. RESULTS: The search strategy resulted in 15,103 articles; finally, 20 articles were included, with 4 reporting longitudinal designs. The detection rate of leprosy ranged from 0.13 to 116.18 per 100,000 patients/year in the USA and Brazil, respectively. In the meta-analysis, the detection rate of cases of leprosy per 100,000 immunosuppressed patients with rheumatic diseases was 84 (detection rate = 0.00084; 95% CI = 0.0000-0.00266; I2 = 0%, p = 0.55). CONCLUSION: Our analysis showed that leprosy was relatively frequently detected in medication-induced immunosuppressed patients suffering from rheumatological diseases, and further studies are needed. The lack of an active search for leprosy in the included articles precluded more precise conclusions. TRIAL REGISTRATION: This review is registered in PROSPERO with the registry number CRD42018116275 .
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Enfermedades Gastrointestinales/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Lepra/diagnóstico , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades Gastrointestinales/patología , Humanos , Inmunosupresores/efectos adversos , Lepra/etiología , Estudios Longitudinales , Enfermedades Reumáticas/patología , Enfermedades de la Piel/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Since the novel coronavirus disease outbreak, over 179.7 million people have been infected by SARS-CoV-2 worldwide, including the population living in dengue-endemic regions, particularly Latin America and Southeast Asia, raising concern about the impact of possible co-infections. METHODS: Thirteen SARS-CoV-2/DENV co-infection cases reported in Midwestern Brazil between April and September of 2020 are described. Information was gathered from hospital medical records regarding the most relevant clinical and laboratory findings, diagnostic process, therapeutic interventions, together with clinician-assessed outcomes and follow-up. RESULTS: Of the 13 cases, seven patients presented Acute Undifferentiated Febrile Syndrome and six had pre-existing co-morbidities, such as diabetes, hypertension and hypopituitarism. Two patients were pregnant. The most common symptoms and clinical signs reported at first evaluation were myalgia, fever and dyspnea. In six cases, the initial diagnosis was dengue fever, which delayed the diagnosis of concomitant infections. The most frequently applied therapeutic interventions were antibiotics and analgesics. In total, four patients were hospitalized. None of them were transferred to the intensive care unit or died. Clinical improvement was verified in all patients after a maximum of 21 days. CONCLUSIONS: The cases reported here highlight the challenges in differential diagnosis and the importance of considering concomitant infections, especially to improve clinical management and possible prevention measures. Failure to consider a SARS-CoV-2/DENV co-infection may impact both individual and community levels, especially in endemic areas.
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COVID-19 , Coinfección , Brasil/epidemiología , Coinfección/epidemiología , Brotes de Enfermedades , Femenino , Humanos , Embarazo , SARS-CoV-2RESUMEN
The precise diagnosis of American tegumentary leishmaniasis (ATL) is an essential task due to the disease's associated morbidity. A noninvasive, extremely sensitive, and highly specific exam is critical, particularly for mucosal leishmaniasis (ML), in which a low parasite quantity is expected. We aimed to compare the diagnostic accuracy of swab and biopsy sample analysis using SYBR Green- and TaqMan-based real-time PCR (qPCR) assays with that of a composite reference standard consisting of the Montenegro skin test, serology, histopathology, smears, culture, and conventional PCR. In total, 55 patients with ATL (ML, 18 patients; cutaneous leishmaniasis [CL], 37 patients) and 36 patients without ATL were studied. qPCR analysis of swabs was more accurate when using SYBR Green (87.88%; 95% confidence interval [CI], 77.86 to 93.73 patients) than when using TaqMan (78.79%; 95% CI, 67.49 to 86.92%) (P = 0.031). SYBR Green (84.72%; 95% CI, 74.68 to 91.25%) was also more accurate than TaqMan (73.61%; 95% CI, 62.42 to 82.41%) for biopsy samples (P = 0.008). All qPCR methods were 100% specific. Swabs and biopsy specimens had similar sensitivity when using the same chemistry (P = 0.125 for SYBR Green and P = 0.625 for TaqMan). Moreover, qPCR achieved better performance than most existing techniques used for the diagnosis of ATL and also detected the Leishmania parasite in a greater proportion of patients than the associated histopathology, smear, culture, and conventional PCR techniques did. Swabs therefore represent a useful diagnostic tool because they not only are noninvasive but also can achieve an accuracy similar to that of biopsy samples. The high accuracy of SYBR Green-based qPCR may also reduce the requirement for associated parasitological tests for ATL diagnosis.
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Enfermedades Endémicas , Leishmania braziliensis/aislamiento & purificación , Leishmaniasis Mucocutánea/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto , Anciano , Benzotiazoles , Biopsia , Diaminas , Femenino , Humanos , Leishmaniasis Mucocutánea/epidemiología , Masculino , Persona de Mediana Edad , Compuestos Orgánicos , Estudios Prospectivos , Quinolinas , Sensibilidad y Especificidad , Coloración y EtiquetadoRESUMEN
The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of a gold standard. An accurate diagnosis is essential because of the high toxicity of the medications for the disease. This study aimed to assess the ability of polymerase chain reaction (PCR) to identify MCL and to compare these results with clinical research recently published by the authors. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement was performed using comprehensive search criteria and communication with the authors. A meta-analysis considering the estimates of the univariate and bivariate models was performed. Specificity near 100% was common among the papers. The primary reason for accuracy differences was sensitivity. The meta-analysis, which was only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59; 0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The search for measures that could increase the sensitivity of PCR should be encouraged. The quality of the collected material and the optimisation of the amplification of genetic material should be prioritised.
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ADN Protozoario/aislamiento & purificación , Leishmaniasis Mucocutánea/diagnóstico , Reacción en Cadena de la Polimerasa/normas , Biopsia , Ensayos Clínicos como Asunto , Intervalos de Confianza , Humanos , Leishmaniasis Mucocutánea/sangre , Leishmaniasis Mucocutánea/orina , Investigación Cualitativa , Curva ROC , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: To analyse the temporal trends and spatiotemporal distribution of leprosy relapse in Brazil from 2001 to 2021. METHODS: An ecological study with a temporal trend approach and space-time analysis of leprosy relapse in Brazil was carried out with data from the Notifiable Diseases Information System. RESULTS: A total of 31 334 patients who experienced leprosy relapse were identified. The number of recurrent cases tended to increase throughout the study period, and this increase was significant among females and in almost all age groups, except for those <15, 50-59 and ≥70 y. Several clusters of high- and low-risk patients were identified across all regions with a heterogeneous distribution. CONCLUSIONS: The burden of relapse showed an increasing trend in some groups and was distributed in all regions.
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Lepra , Recurrencia , Análisis Espacio-Temporal , Humanos , Brasil/epidemiología , Femenino , Lepra/epidemiología , Masculino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Niño , Preescolar , LactanteRESUMEN
Brazil has the second largest number of leprosy cases (a disease with a significant burden) in the world. Despite global and local efforts to eliminate this public health problem, inadequate or late diagnosis contribute to perpetuate its transmission, especially among household contacts. Tests such as the rapid IgM antibody detection (RT) and real-time polymerase chain reaction (RT-PCR) were developed to overcome the challenges of early diagnosis of leprosy. This study aimed to analyze the cost-effectiveness of a new diagnostic algorithm recommended by the Brazilian government to diagnose leprosy in household contacts of confirmed leprosy cases, which includes the RT and RT-PCR tests. A decision tree model was constructed and the perspective of the Brazilian Unified National Health System (SUS) and a 1-year time horizon were adopted. Only direct medical costs related to diagnostic tests were included. Effectiveness was measured as the number of avoided undiagnosed leprosy cases. Different scenarios were analyzed. The sequential use of RT, slit-skin smear (SSS) microscopy, and RT-PCR as recommended by the Brazilian Ministry of Health was compared to a base case (isolated SSS microscopy), yielding an incremental cost-effectiveness ratio of USD 616.46 per avoided undiagnosed leprosy case. Univariate sensitivity analysis showed that the prevalence of leprosy among household contacts was the variable that influenced the model the most. This is the first economic model to analyze a diagnostic algorithm of leprosy. Results may aid managers to define policies and strategies to eradicate leprosy in Brazil.
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Análisis de Costo-Efectividad , Lepra , Humanos , Brasil/epidemiología , Algoritmos , Comercio , Lepra/diagnóstico , Lepra/epidemiologíaRESUMEN
BACKGROUND: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. OBJECTIVE: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. METHODS: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. RESULTS: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01â1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29â3.08; p = 0.002) were associated with treatment interruption. STUDY LIMITATIONS: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. CONCLUSIONS: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.
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Interleucina-6 , Psoriasis , Humanos , Estudios de Cohortes , Calidad de Vida , Interrupción del Tratamiento , Psoriasis/patología , BiomarcadoresRESUMEN
Introduction: The present study aimed to evaluate leprosy cure and relapse rates as primary outcomes related to two additional strategies for leprosy treatment: clofazimine for paucibacillary (PB) leprosy patients and clarithromycin for patients with rifampicin-resistant leprosy. Methods: We conducted two systematic reviews (protocols CRD42022308272 and CRD42022308260). We searched the PubMed, EMBASE, Web of Science, Scopus, LILACS, Virtual Health Library and Cochrane Library databases, registers of clinical trial databases and gray literature. We included clinical trials evaluating the addition of clofazimine to PB leprosy treatment and the use of clarithromycin for treating patients with rifampicin-resistant leprosy. Risk of bias (RoB) in randomized clinical trials was assessed by the RoB 2 tool and that in non-randomized clinical trials was assessed by the ROBINS-I tool; and the certainty of the evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. A meta-analysis of dichotomous outcomes was performed. Results: For clofazimine, four studies were included. Cure and relapse rates were not different with the addition of clofazimine to PB leprosy treatment and demonstrated very low certainty of evidence. For clarithromycin, six studies were included. Considerable heterogeneity resulted from the difference between comparators, and studies showed no difference in the assessed outcomes with the addition of clarithromycin to rifampicin-resistant leprosy treatment. Mild adverse events were reported for both drugs but did not significantly impact treatment. Discussion: The effectiveness of both drugs still needs to be determined. Adding clofazimine to PB leprosy treatment may reduce the repercussions of an incorrect operational classification with no apparent relevant side effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308272; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308260, identifier: CRD42022308272; CRD42022308260.
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Leprosy is an infectious and contagious disease of slow evolution, triggered by Mycobacterium leprae. Arthritis is its third most common manifestation, after cutaneous and peripheral nerve involvement. Since musculoskeletal symptoms may be the initial presentation of the disease, it is important for health professionals to recognize its rheumatic manifestations for early diagnosis and appropriate treatment, especially in endemic areas. In addition, cases of leprosy have increased globally, notably in patients undergoing treatment with TNF-α blockers and due to the increase in migration and travel of people from developing countries to developed countries. This review proposes to discuss the main scenarios of mimicry of different rheumatic diseases by leprosy, as well as the role of immunosuppressive drugs used in rheumatology practice in the treatment of reactional states and in the risk of developing the infection.
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BACKGROUND: The success of tungiasis treatment is highly dependent on adequate environmental control. METHODS: This is a real-world observational cohort study designed to monitor the effectiveness of topical dimethicone together with a One Health approach for the control of tungiasis in the Sanumás communities, Amazon rainforest, Brazil. We followed up on 562 indigenous people and 81 domestic dogs for 1.5 years in a 3-month interval. A new molecular method for large-scale soil evaluation was also tested. The control of tungiasis was independently conducted by the Brazilian Ministry of Health and comprised topical dimethicone application (NYDA®) for humans, single-dose oral afoxolaner for dogs, and in-house soil fumigation with fipronil. The main outcome was the occurrence of tungiasis after the use of topical dimethicone together with the One Health approach. RESULTS: A total of 49 of the 562 indigenous people had active tungiasis at enrollment (8.72%). Only three cases of tungiasis resulted in active lesions after the use of topical dimethicone together with the One Health approach, with two cases of recurrence. From the 6-month follow-up and after, soil infestation was not detected. CONCLUSIONS: We conclude that the use of NYDA® together with animal and environmental interventions are effective measures for the control of tungiasis.
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Background: SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection. Methods: We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content. Results: A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001. Conclusion: This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.
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BACKGROUND: Tungiasis is a disease associated with extreme poverty. We aimed to evaluate the prevalence of tungiasis in six different settlements of the Sanumás indigenous community in a remote area in the Auaris region, Yanomami territory, Brazil. METHODS: We conducted an observational study to detect clinical and epidemiological factors associated with tungiasis using a cross-sectional strategy and multivariate logistic regression. Soil analysis was performed by visual and microscopic methods. RESULTS: We examined 555 persons, 45 of whom had active tungiasis; 18 cases were classified as mild, 16 as moderate and 11 as severe. The disease was significantly more prevalent in children than in adults (odds ratio (OR) 15.77; 95% confidence interval (CI) = 5.34-67.91; p < 0.001). Soil infestation was significantly related to the occurrence of human tungiasis (OR = 12.29; 95% CI = 3.75-45.88). The sex and GPS location of the houses were not related to the occurrence of tungiasis. CONCLUSIONS: We conclude that tungiasis is an important problem in the Sanumás community, especially for children. We suggest that interruption of the off-host transmission cycle, together with regular treatment [human and animal interventions], must be prioritized to achieve control of tungiasis in indigenous populations.
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Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.
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COVID-19 , Mujeres Embarazadas , Humanos , Embarazo , Femenino , Interleucina-17 , COVID-19/terapia , Interleucina-6 , Estudios Transversales , SARS-CoV-2 , Citocinas , Quimiocinas , Resultado del EmbarazoRESUMEN
Congenital dermatofibrosarcoma protuberans (DFSP) is a rare dermal and subcutaneous neoplasm of low-grade malignant behavior that is characterized by a low frequency of metastases with locally invasive growth. Its occurrence at birth and during childhood is rare. We present a case of a patient who was born with a light brown macule on his right buttock that was misdiagnosed as localized scleroderma. The lesion progressed into reddish atrophic plaques and nodules extending to the iliac region and the gluteal fold. At 5 years of age, a diagnosis of congenital DFSP was made based on clinical and immunohistochemical characteristics (CD34 positivity and spindle cell proliferation). Although there was a delay in diagnosis, a 3-step excision was proposed with a final step of Mohs micrographic surgery (MMS).
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Dermatofibrosarcoma/diagnóstico , Errores Diagnósticos , Neoplasias Cutáneas/diagnóstico , Preescolar , Dermatofibrosarcoma/congénito , Dermatofibrosarcoma/cirugía , Humanos , Inmunohistoquímica , Masculino , Neoplasias Cutáneas/congénito , Neoplasias Cutáneas/cirugíaRESUMEN
Patients with leprosy may experience a chronic and severe type II leprosy reaction (ENL) erythema nodosum leprosum that may not respond to thalidomide and systemic immunosuppressants or may even cause serious adverse events. We here present four patients in whom anti-TNF-α therapy was used with successful results and compare our findings with other published cases. Four patients with chronic and severe ENL who did not respond to, at least, thalidomide and steroids (high doses) were followed up at two reference centers in Brazil. A thorough laboratory investigation was performed to exclude tuberculosis and other diseases before the start of immunobiological medication. Three patients were started on etanercept, and one patient was started on adalimumab. Of all patients, three developed severe adverse events resulting from the use of classical immunosuppressants for ENL (cataracts, deep vein thrombosis, diabetes, and osteoporosis). In all cases, a reduction in the number of ENL and, at least half of the immunosuppressant dose between 6 months and 2 years, were observed. Long-term follow-up of one patient revealed a dramatic reduction in hospital admissions due to ENL, from 12 instances in 1 year (before biologic therapy) to none (after biologic therapy), along with an improvement in condyloma acuminatum. In addition, no direct adverse events were observed with biologics. Treatment with anti-TNF-α therapy may be used as an alternative in patients with chronic and severe ENL who do not respond to traditional treatment (e.g., thalidomide, steroids, and other immunosuppressants). This treatment can help reduce the frequency of ENL, the immunosuppressive burden, and the number of hospital admissions.