Publications by authors named "Ciro Gomes"

60 Publications

Case Report: A Case Series of Immunobiological Therapy (Anti-TNF-α) for Patients With Erythema Nodosum Leprosum.

Front Med (Lausanne) 2022 24;9:879527. Epub 2022 Jun 24.

Dermatologia, Hospital de Doenças Tropicais, Goiânia, Brazil.

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.
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http://dx.doi.org/10.3389/fmed.2022.879527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263440PMC
June 2022

Cerebrospinal fluid analysis of pregnant women at early stages of COVID-19.

Taiwan J Obstet Gynecol 2022 Jul 23;61(4):672-674. Epub 2022 May 23.

Department of Obstetrics and Gynecology, University of Brasília, Brasília, Brazil.

Objective: To determine the presence or absence of SARS-CoV-2 in the cerebrospinal fluid of pregnant women at early stages of COVID-19.

Materials And Methods: We conducted a prospective observational study with pregnant women undergoing cesarean section and real-time polymerase chain reaction to SARS-CoV-2 was performed in the cerebrospinal fluid in the early stages of COVID-19.

Results: Fourteen pregnant women, whose COVID-19 symptoms started between four to 18 days prior to delivery, were included. Eleven of the women reported anosmia, dysgeusia, and headaches and there were two fatal cases. SARS-Cov-2 was not present in the cerebrospinal fluid of these COVID-19 patients with early neurological symptoms, even in severe cases.

Conclusion: Our study suggests that peripheric cell damage and parainfectious phenomena may predominate over direct central nervous system injury in the pathophysiology of COVID-19 related early neurological symptoms on pregnant women.
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http://dx.doi.org/10.1016/j.tjog.2022.03.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124920PMC
July 2022

Hansen's disease and COVID-19 co-infection in Brazil.

Int J Dermatol 2022 Jul 1. Epub 2022 Jul 1.

Programa de Pós-Graduação em Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Brazil.

Background: The implications of COVID-19 co-infection in patients under treatment for Hansen's disease (HD, leprosy) remain uncertain. We aimed to describe clinical characteristics, treatments, and outcomes in patients with HD and COVID-19 in Brazil.

Methods: Cross-sectional study recruiting adult HD patients with PCR-confirmed COVID-19 from five HD treatment centers in Brazil between March 1, 2020, and March 31, 2021. At the time of this study, no patient had received COVID-19 vaccine.

Results: Of 1377 patients under treatment for HD, 70 (5.1%) were diagnosed with COVID-19. Of these, 41 (58.6%) had PCR-confirmed COVID-19, comprising 19 men and 22 women, aged 24-67 (median 45) years. HD was multibacillary in 39/41 patients. Eight patients ceased WHO Multi-Drug Therapy for HD, three for lack of drugs, two because of COVID-19, and three for other reasons. Of the 33 who continued treatment, 26 were on the standard regimen and seven an alternative regimen. Seventeen patients were receiving oral prednisone, including nine patients with type 1 reaction, four with type 2 reaction, three with neuritis, and one with rheumatologic disease. Twelve patients were hospitalized for COVID-19, and six patients died, of whom three had hypertension and one also had type 2 diabetes and obesity.

Conclusions: COVID-19 and Hansen's disease co-infection did not appear to change the clinical picture of either disease in this cross-sectional study. The wider impact of the pandemic on persons affected by HD requires follow-up and monitoring.
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http://dx.doi.org/10.1111/ijd.16319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349626PMC
July 2022

Sensitivity of different DNA extraction methods and PCR to detect resistance in patients with leprosy stratified by the bacilloscopic index.

Braz J Infect Dis 2022 Jun 27;26(4):102381. Epub 2022 Jun 27.

Faculdade de Medicina, Programa de Pós-graduação em Ciências Médicas, Universidade de Brasília, Brasília, DF, Brazil; Universidade de Brasília, Hospital Universitário de Brasília, Brasília, DF, Brazil; Núcleo de Medicina Tropical, Universidade de Brasília, Brasília, DF, Brazil. Electronic address:

Introduction: Antimicrobial resistance in leprosy is an emerging problem, and the quantitative impact of low bacilloscopic indexes (BIs) on the sensitivity of molecular tests is unknown. We aimed to evaluate the sensitivity of gene sequencing for the detection of mutations related to antimicrobial resistance in Mycobacterium leprae in patients with low BIs using an analytical model.

Methods: Patients with leprosy were included and divided into two groups depending on their BIs (≥ 2+ and < 2+). The sensitivities of the two DNA extraction methods were compared after amplifying and sequencing the repetitive element (RLEP), folP1, rpoB and gyrA in M. leprae.

Results: We included 56 patients with leprosy: 35 had BIs less than 2+ (22 had negative slit-skin smear [SSS] results) and 21 patients had BIs greater than or equal to 2+. The sensitivity of the amplification of the RLEP target and the gene sequencing of folP1, rpoB and gyrA was 50 to 70% lower in patients with a BI less than 2+ and was significantly reduced in patients with lower BIs for all targets (p < 0.001). One patient had a mutation in the folP1 gene, and 14 patients had mutations in the gyrA gene, but no mutations related to antimicrobial resistance were found.

Conclusions: We can conclude that the sensitivity of molecular tests is directly related to the BI, but these tests can still detect up to 20% of the targets in patients with BIs < 2+. New strategies to improve the sensitivity for detecting antimicrobial resistance in leprosy patients and reasonable clinical criteria for follow-up and the introduction of alternative treatments must be developed.
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http://dx.doi.org/10.1016/j.bjid.2022.102381DOI Listing
June 2022

Impact of COVID-19 on the mental health of public university hospital workers in Brazil: A cohort-based analysis of 32,691 workers.

PLoS One 2022 16;17(6):e0269318. Epub 2022 Jun 16.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, Brazil.

Background: In early 2020, the COVID-19 pandemic paralyzed the world and exposed the fragility of health systems in the face of mass illness. Health professionals became protagonists, fulfilling their mission at the risk of physical and mental illness. The study aimed to evaluate absenteeism indirectly related to SARS-CoV-2 infection in a large population of health care professionals.

Methods: An observational longitudinal repeated measures study was performed, including workers linked to 40 public university hospitals in Brazil. All causes of absenteeism were analyzed, focusing on those not directly attributed to COVID-19. Results for the same population were compared over two equivalent time intervals: prepandemic and during the pandemic.

Findings: A total of 32,691 workers were included in the study, with health professionals comprising 82.5% of the sample. Comparison of the periods before and during the pandemic showed a 26.6% reduction in work absence for all causes, except for COVID-19 and mental health-related absence. Concerning work absence related to mental health, the odds ratio was 39.0% higher during the pandemic. At the onset of the pandemic, there was an increase in absenteeism (all causes), followed by a progressive reduction until the end of the observation period.

Interpretation: Work absence related to mental illness among health care professionals increased during the COVID-19 pandemic, highlighting the need for health care managers to prioritize and implement support strategies to minimize absenteeism.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269318PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202958PMC
June 2022

No evidence for cardiotoxicity of miltefosine - Reply.

An Bras Dermatol 2022 Jul-Aug;97(4):549-550. Epub 2022 Jun 3.

Faculty of Medicine, Universidade de Brasília, Brasília, DF, Brazil.

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http://dx.doi.org/10.1016/j.abd.2022.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263635PMC
July 2022

Can Leprosy Reaction States Mimic Symptoms of Fibromyalgia? A Cross-Sectional Analytical Study.

Front Med (Lausanne) 2022 25;9:870584. Epub 2022 Apr 25.

Programa de Pós-Graduação em Medicina Tropical, Faculdade de Medicina, Universidade de Brasília, Brasilia, Brazil.

Leprosy causes significant pain in affected patients, especially those experiencing reactional states. Fibromyalgia is characterized by widespread pain and is often accompanied by fatigue. Confusion between the clinical manifestations of fibromyalgia and those of leprosy reactions is possible at the primary care level, the first contact with the health system in most cases. We aimed to determine whether the presence of leprosy reactional states is related to the development of signs and symptoms included in the case definition of fibromyalgia and establish recommendations for obtaining the correct diagnosis. We performed a cross-sectional study in which the main independent variable was the presence of any leprosy reactional state and the primary dependent variable was the diagnosis of fibromyalgia according to the 2016 Revisions of the 2010/2011Fibromyalgia Provisional Criteria of the American College of Rheumatology. Forty-three patients were included in the study. Twenty-eight (65.12%) patients had a type I reactional state, only 1 (2.33%) had an isolated type II reactional state, and 5 (11.63%) had both type I and type II reactional states. Only 2 patients who suffered from cooccurring type I and II reactional states obtained sufficient scores for the diagnosis of fibromyalgia. Although diffuse pain was common in leprosy patients, none of the types of reactional states were associated with a higher frequency of criteria for fibromyalgia. We can conclude that a leprosy reactional state is probably not a risk factor for fibromyalgia but can act as a confounder, as tender points may be similar in both diagnoses. In patients diagnosed with fibromyalgia, leprosy must be considered in the differential diagnosis in endemic regions.
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http://dx.doi.org/10.3389/fmed.2022.870584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082667PMC
April 2022

Antimicrobial Resistance among Leprosy Patients in Brazil: Real-World Data Based on the National Surveillance Plan.

Antimicrob Agents Chemother 2022 05 18;66(5):e0217021. Epub 2022 Apr 18.

Programa de Pós-Graduação em Saúde Coletiva, Faculdade de Medicina, Universidade de Brasília - UnB, Brasília, Brazil.

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 (), rifampin (), and ofloxacin resistance () 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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http://dx.doi.org/10.1128/aac.02170-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112907PMC
May 2022

Standardization of SYBR Green-Based Real-Time PCR Through the Evaluation of Different Thresholds for Different Skin Layers: An Accuracy Study and Track of the Transmission Potential of Multibacillary and Paucibacillary Leprosy Patients.

Front Microbiol 2021 7;12:758222. Epub 2021 Dec 7.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, Brazil.

The development of new molecular techniques is essential for the early diagnosis of leprosy. Studies in the field have failed to elucidate the performance of these tests in clinical practice. We aimed to design a new primer pair for the repetitive element (RLEP) target of and to test the accuracy of SYBR green-based real-time PCR through the evaluation of different thresholds for different skin layers. We also aimed to track the transmission potential of multibacillary and paucibacillary leprosy patients. The validation of our reaction resulted in a quantification limit of 0.03 bacilli. We then conducted a cross-sectional/cohort-based study of diagnostic accuracy. Patients were included, and skin samples were divided into four layers: epidermis, superior dermis, inferior dermis, and hypodermis. We also quantified in nasal swabs of the included patients and compared the results to the number of household contacts also diagnosed with leprosy. One hundred patients with a clinical presentation compatible with leprosy were allocated to the leprosy or control group. Although the parasite load was greater in the superior and inferior dermis, DNA was found in all skin layers. The best sensitivity was observed for the superior dermis using the presence of any quantifiable bacillus DNA as the threshold [sensitivity=59.26% (95% CI=45.97-71.32)]. In the epidermis, setting 1 quantifiable bacillus as the threshold resulted in 100% specificity (95% CI=92.29-100). The number of bacilli found in nasal swabs was not significantly related to the number of household contacts also diagnosed with leprosy. Paucibacillary patients tested positive only for bacillus fragments in nasal swabs but not for the entire bacilli. We can conclude that superficial biopsies might result in sensitivity loss, although different skin sample types will have little influence on the final accuracy. In contrast, threshold changes greatly influence these properties. Paucibacillary patients may not be a relevant source of disease transmission.
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http://dx.doi.org/10.3389/fmicb.2021.758222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753983PMC
December 2021

Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention.

PLoS One 2022 14;17(1):e0262600. Epub 2022 Jan 14.

Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina da Universidade de Brasília (UnB), Brasília, Distrito Federal, Brazil.

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262600PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759688PMC
January 2022

Dramatic secukinumab-mediated improvements in refractory leprosy-related neuritis via the modulation of T helper 1 (Th1) and T helper 17 (Th17) immune pathways.

Rev Soc Bras Med Trop 2021 17;54:e03362021. Epub 2021 Dec 17.

Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, DF, Brasil.

A 39-year-old woman was diagnosed with relapsed multibacillary leprosy and refractory neuritis. Here, we describe an evident loss of therapeutic effectiveness after the third pulse of corticosteroids, which may be attributed to tachyphylaxis and the posterior modulation of interferon- γ (IFN-γ), tumor necrosis factor- α (TNF-α,) interleukin-17A (IL-17A), and IL-12/23p40 after the induction phase of secukinumab. In this case, plasma cytokine analysis showed that secukinumab induced a reduction in IL-17 concomitant with impressive clinical improvements in the patient's neural function. Interestingly, secukinumab induced reductions in cytokines related to Th1 responses and earlier stages of the Th17 response, including IL-23/12.
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http://dx.doi.org/10.1590/0037-8682-0336-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687500PMC
December 2021

The Presence of DNA in the Nasal Mucosa of Cutaneous Leishmaniasis Patients and the Search for Possible Clinical and Immunological Patterns of Disease Progression: A Cross Sectional Study.

Front Cell Infect Microbiol 2021 14;11:744163. Epub 2021 Oct 14.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, Brazil.

is the most important causal agent of American tegumentary leishmaniasis (ATL), and 3 to 5% of patients develop mucosal lesions. The mechanisms related to parasite and host immune interactions and the parasite life cycle that lead to dissemination to the mucosa are poorly understood. We aimed to detect DNA in the nasal mucosa of cutaneous leishmaniasis (CL) patients with early mucous dissemination and to relate those findings to specific inflammatory responses. Nasal swabs were collected from patients with the cutaneous form of ATL. DNA was investigated using TaqMan-based real-time PCR. The levels of serum cytokines (IL-12, IL-6, TNF-α, IL-10, IL-1β and IL-8) were measured by a multiplex cytometric array. A Poisson regression model was used to test prevalence ratios (PRs) and multivariate interactions of clinical and laboratory characteristics. Of the 79 CL patients, 24 (30%) had DNA in the nasal mucosa. In the multivariate model, parasite DNA presence in mucosa was associated with a reduction in IL-12 levels (PR = 0.440; p=0.034), increased IL-6 levels (PR = 1.001; p=0.002) and a higher number of affected body segments (PR = 1.65; p<0.001). In this study, we observed a higher rate of early dissemination to the nasal mucosa than what was previously described. We suggest that an enhanced Th1 profile characterized by higher IL-12 is important for preventing dissemination of to the mucosa. Further evaluation of parasite-related interactions with the host immunological response is necessary to elucidate the dissemination mechanisms of .
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http://dx.doi.org/10.3389/fcimb.2021.744163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551912PMC
November 2021

The efficacy of topical, oral and surgical interventions for the treatment of tungiasis: A systematic review of the literature.

PLoS Negl Trop Dis 2021 08 20;15(8):e0009722. Epub 2021 Aug 20.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, Brazil.

Background: Tungiasis is a neglected disease caused by Tunga penetrans that can be complicated by secondary infections and local tissue destruction. Adequate treatment is important, especially in vulnerable populations; potential treatment options proposed range from surgical extraction to the use of oral and topical medications. We aimed to perform a systematic review to assess the efficacy of topical, oral and surgical interventions for the treatment of tungiasis.

Methodology/principal Findings: The present review is registered in PROSPERO (CRD42021234741). On September 1, 2020, we searched PubMed, EMBASE, Scopus, Web of Science, Science Direct, Scielo and LILACS BVS. We included clinical trials and longitudinal observational studies that evaluated any topical, systemic or mechanical treatment for tungiasis. We used the Revised Cochrane Risk of Bias (RoB) Tool for Randomized Trials for clinical trial analysis. Qualitative and quantitative descriptive syntheses were performed. Our search strategy resulted in 3376 references. Subsequently, 2568 titles/abstracts and 114 full texts were screened. We finally included 19 articles; 9 were classified as clinical trials. Two and 3 articles presented low and some RoB, respectively, according to the tool. Only two articles tested the efficacy of oral medications (niridazole, ivermectin), with discouraging results. Six clinical trials evaluated topical products for the treatment of tungiasis; 2 evaluated dimeticone-based compounds and reported positive results in lesion reduction and cure. None reported significant adverse reactions. Surgical extraction was evaluated only in observational studies.

Conclusions/significance: We conclude that, although surgical extraction is the most commonly used treatment, there is sufficient evidence supporting the use of occlusive agents, especially manufactured dimeticone-based products.
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http://dx.doi.org/10.1371/journal.pntd.0009722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409605PMC
August 2021

SARS-CoV-2/DENV co-infection: a series of cases from the Federal District, Midwestern Brazil.

BMC Infect Dis 2021 Jul 31;21(1):727. Epub 2021 Jul 31.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília - UnB, Brasília, Brazil.

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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http://dx.doi.org/10.1186/s12879-021-06456-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325531PMC
July 2021

Defective Allele of the Neuronal Nitric Oxide Synthase Gene Increases Insulin Resistance During Acute Phase of Myocardial Infarction.

Int J Gen Med 2021 20;14:3669-3676. Epub 2021 Jul 20.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, DF, Brazil.

Background: Glycemic disorders are strong predictors of mortality in ST-elevation myocardial infarction (STEMI) patients, and disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether a defective allele of the neuronal nitric oxide synthase (nNOS) gene () might influence insulin response and blood-glucose balance during the acute phase of STEMI and if post-infarction total plasma-NO levels and vasodilation scores varied across nNOS genotypes.

Methods: Consecutive patients with STEMI (n=354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. In-hospital clinical and blood evaluations were performed at admission and five days after STEMI, with glycemic, insulinemic, and disposition indices assessed at the same times. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day.

Results: Homozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity on day 1 while showing the highest β-cell function and no changes in the circulating NO pool, which is compatible with hyperresponsive β cells counteracting the inherent glucose-resistant state of AA patients. At day 5, glycemic scores had shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a significant yet poor increase in NO bioavailability compared to that among G carriers. All in all, defective homozygotes showed greater insulin resistance at admission that had reversed by 5 days after STEMI. Even so, A carriers developed lower FMD scores compared to G homozygotes after the acute phase.

Conclusion: A defective nNOS allele (and due decline in NO production) seemed to elicit a hyperinsulinemia response to compensate for an insulin-resistant state during the acute phase of STEMI and to be associated with poor endothelial function after the acute phase.
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http://dx.doi.org/10.2147/IJGM.S313661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312503PMC
July 2021

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study.

PLoS Negl Trop Dis 2021 07 28;15(7):e0009635. Epub 2021 Jul 28.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, Brazil.

Background: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19.

Methodology/principal Findings: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19.

Conclusions/significance: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.
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http://dx.doi.org/10.1371/journal.pntd.0009635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351963PMC
July 2021

A Pilot Randomized Clinical Trial: Oral Miltefosine and Pentavalent Antimonials Associated With Pentoxifylline for the Treatment of American Tegumentary Leishmaniasis.

Front Cell Infect Microbiol 2021 1;11:700323. Epub 2021 Jul 1.

Pós-Graduação de Ciências da Saúde da Faculdade de Ciências Saúde, Universidade de Brasília, Brasília, Brazil.

Introduction: American tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a analysis.

Methods: A pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days.

Results: Forty-three patients were included: 25 with ML and 18 with CL caused by . AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058).

Conclusion: In this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.
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http://dx.doi.org/10.3389/fcimb.2021.700323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281031PMC
July 2021

Non-tuberculous cutaneous mycobacterioses.

An Bras Dermatol 2021 Sep-Oct;96(5):527-538. Epub 2021 Jul 16.

Postgraduate Program in Tropical Medicine, Universidade de Brasília, Brasília, DF, Brazil; Postgraduate Program in Medical Sciences, Universidade de Brasília, Brasília, DF, Brazil. Electronic address:

Non-tuberculous mycobacteriosis, previously known as atypical, anonymous, opportunistic, or unclassified mycobacteriosis, refers to pathogenic mycobacterioses other than those caused by Mycobacterium tuberculosis and Mycobacterium leprae. These mycobacteria are known for their environmental distribution, mainly in water and soil. The incidence of non-tuberculous mycobacteriosis has been increasing in all countries and skin infections are being increasingly studied, mainly with the increase in immunosuppressive conditions and the development of new medications that affect immunological function. In the present article, a detailed narrative review of the literature is carried out to study the main non-tuberculous mycobacteriosis that cause diseases of the skin and appendages. The article also aims to present a historical context, followed by epidemiological, microbiological, and clinical characteristics of these diseases. Practical considerations about the diagnosis and treatment of non-tuberculous mycobacteriosis are detailed.
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http://dx.doi.org/10.1016/j.abd.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441525PMC
September 2021

Comparison of cardiotoxicity between N-methyl-glucamine and miltefosine in the treatment of American cutaneous leishmaniasis.

An Bras Dermatol 2021 Jul-Aug;96(4):502-504. Epub 2021 May 15.

Universidade de Brasília, Brasília, DF, Brazil; Hospital Universitário de Brasília, Universidade de Brasília, Brasília, DF, Brazil.

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http://dx.doi.org/10.1016/j.abd.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245708PMC
July 2021

Leprosy detection rate in patients under immunosuppression for the treatment of dermatological, rheumatological, and gastroenterological diseases: a systematic review of the literature and meta-analysis.

BMC Infect Dis 2021 Apr 13;21(1):347. Epub 2021 Apr 13.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília - UnB, Campus Universitário Darcy Ribeiro, Brasília, DF, CEP 70910-900, Brazil.

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; I = 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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http://dx.doi.org/10.1186/s12879-021-06041-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045377PMC
April 2021

Older drivers are at increased risk of fatal crash involvement: Results of a systematic review and meta-analysis.

Arch Gerontol Geriatr 2021 Jul-Aug;95:104414. Epub 2021 Apr 6.

University of Brasilia, Multidisciplinary Center for the Aged, Brasília, DF, Brazil. Electronic address:

Older adults have become a larger part of the driving population, but whether they are at increased risk of being involved in fatal crashes remains unclear.

Methods: We performed a systematic review of studies investigating fatal crash involvement of older vs non-older drivers by searching the following databases: PubMed, Cochrane Library, Embase, LILACS, SciELO, Web of Science, and ProQuest. Studies that used fatal crash involvement rates per distance driven as a measure of frequency were selected for meta-analysis.

Results: We analyzed 14 studies published between 2001 and 2018. Of these, 12 reported a higher rate of fatal crashes involving older drivers than non-older drivers; 9 of them used involvement rates per distance driven, which is considered the most appropriate metric. The meta-analysis revealed high heterogeneity between studies. The meta-regression attributed 40% of the heterogeneity to age (older vs non-older drivers) (p<0.005).

Conclusion: Age appears to be associated with higher driver involvement rates for fatal crashes among older persons.
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http://dx.doi.org/10.1016/j.archger.2021.104414DOI Listing
June 2021

Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection (PROUDEST Trial): Protocol for a Multicenter, Prospective Cohort Study.

JMIR Res Protoc 2021 Apr 20;10(4):e26477. Epub 2021 Apr 20.

Faculty of Medicine, University of Brasília, Brasília - DF, Brazil.

Background: A growing body of evidence suggests that SARS-COV-2 infection during pregnancy may affect maternal-fetal outcomes and possibly result in implications for the long-term development of SARS-CoV-2-exposed children.

Objective: The PROUDEST (Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study) is a multicenter, prospective cohort study designed to elucidate the repercussions of COVID-19 for the global health of mothers and their children.

Methods: The PROUDEST trial comprises 2 prospective, sequential substudies. The PREGNANT substudy will clinically assess the effects of SARS-CoV-2 infection on pregnancy, childbirth, and puerperium from a mechanistic standpoint to elucidate the pregnancy-related inflammatory and immunological phenomena underlying COVID-19. Pregnant women aged 18-40 years who have been exposed (proven with laboratory tests) to SARS-CoV-2 (group A; n=300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B; n=300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study that will assess the offspring of women who enrolled in the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children's growth, neurodevelopment, and metabolism from birth up to 5 years of age. It includes two comparison groups; group A (exposed; n=300) comprises children born from SARS-CoV-2-exposed pregnancies, and group B (controls; n=300) comprises children born from nonexposed mothers.

Results: Recruitment began in July 2020, and as of January 2021, 260 pregnant women who were infected with SARS-CoV-2 during pregnancy and 160 newborns have been included in the study. Data analysis is scheduled to start after all data are collected.

Conclusions: Upon completion of the study, we expect to have comprehensive data that will provide a better understanding of the effects of SARS-CoV-2 infection and related inflammatory and immunological processes on pregnancy, puerperium, and infancy. Our findings will inform clinical decisions regarding the care of SARS-CoV-2-exposed mothers and children and support the development of evidence-based public health policies.

Trial Registration: Brazilian Register of Clinical Trials RBR65QXS2; https://ensaiosclinicos.gov.br/rg/RBR-65qxs2.

International Registered Report Identifier (irrid): DERR1-10.2196/26477.
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http://dx.doi.org/10.2196/26477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059788PMC
April 2021

Molecular and Cellular Biomarkers of COVID-19 Prognosis: Protocol for the Prospective Cohort TARGET Study.

JMIR Res Protoc 2021 Mar 4;10(3):e24211. Epub 2021 Mar 4.

Programa de Pós-graduação em Ciências Médicas da Faculdade de Medicina, University of Brasília, Brasilia, Brazil.

Background: Since the beginning of the COVID-19 pandemic, the world's attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths.

Objective: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19.

Methods: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction-confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care.

Results: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase.

Conclusions: This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008).

Trial Registration: Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk.

International Registered Report Identifier (irrid): DERR1-10.2196/24211.
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http://dx.doi.org/10.2196/24211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935398PMC
March 2021

A systematic review and meta-analysis of studies on the diagnostic accuracy and screening of tests to detect antimicrobial resistance in leprosy.

Diagn Microbiol Infect Dis 2021 May 27;100(1):115325. Epub 2021 Jan 27.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília - UnB, Brasília, Brazil; Programa de Pós-Graduação em Medicina Tropical, Núcleo de Medicina Tropical, Universidade de Brasília - UnB, Brasília, Brazil. Electronic address:

Although multidrug therapy is considered an effective treatment for leprosy, antimicrobial resistance is a serious concern. We performed a systematic review of studies on the diagnostic accuracy and screening of tests for antimicrobial resistance in leprosy. This review was registered in PROSPERO (CRD42020177958). In April 2020, we searched for studies in the PubMed, EMBASE, Web of Science, Scopus, Scielo, and LILACS databases. A random effects regression model was used for the meta-analysis. We included 129 studies. Molecular tests for dapsone resistance had a sensitivity of 78.8% (95% confidence interval [CI] = 65.6-87.9) and a specificity of 97.0% (95% CI = 94.0-98.6). Molecular tests for rifampicin resistance had a sensitivity and specificity of 88.7% (95% CI = 80.0-93.9) and 97.3% (95% CI = 94.3-98.8), respectively. Molecular tests for ofloxacin resistance had a sensitivity and specificity of 80.9% (95% CI = 60.1-92.3) and 96.1% (95% CI = 90.2-98.5), respectively. In recent decades, no increase in the resistance proportion was detected. However, the growing number of resistant cases is still a clinical concern.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115325DOI Listing
May 2021

Mental Health and Burnout Syndrome Among Postgraduate Students in Medical and Multidisciplinary Residencies During the COVID-19 Pandemic in Brazil: Protocol for a Prospective Cohort Study.

JMIR Res Protoc 2021 Jan 19;10(1):e24298. Epub 2021 Jan 19.

Universidade de Brasília - UnB, Brasília, Brazil.

Background: The COVID-19 pandemic has led to high levels of physical, psychological, and social stress among health care professionals, including postgraduate students in medical and multidisciplinary residencies. This stress is associated with the intense fear of occupational exposure to SARS-CoV-2, the virus known to cause COVID-19. These professionals are at risk of developing physical and mental illnesses not only due to the infection but also due to prolonged exposure to multidimensional stress and continued work overload.

Objective: This study aims to evaluate the prevalence of symptoms suggestive of mental disorders and burnout syndrome and determine the risk factors for burnout among postgraduate students in medical and multidisciplinary residencies in Brazil during the COVID-19 pandemic.

Methods: For this prospective cohort study with parallel groups, participants were recruited between July and September 2020 to achieve a sample size of at least 1144 participants. Research instruments such as Depression, Anxiety, and Stress Scale; Patient Health Questionnaire; Brief Resilient Coping Scale; and Oldenburg Burnout Inventory will be used to collect data. Data will be collected in 2 waves: the first wave will include data related to sample characterization and psychosocial evaluation, and the second wave will be launched 12 weeks later and will include an evaluation of the incidence of burnout as well as correlations with the potential predictive factors collected in the first wave. Additionally, we will collect data regarding participants' withdrawal from work.

Results: The recruitment took place from July 29 to September 5, 2020. Data analyses for this phase is already in progress. The second phase of the study is also in progress. The final data collection began on December 1, 2020, and it will be completed by December 31, 2020.

Conclusions: We believe the findings of this study will help evaluate the impact of the COVID-19 pandemic on the mental health conditions of health professionals in Brazil as well as contribute to the planning and implementation of appropriate measures that can alleviate these mental health challenges.

International Registered Report Identifier (irrid): DERR1-10.2196/24298.
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http://dx.doi.org/10.2196/24298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817252PMC
January 2021

A retrospective cohort study of the effectiveness and adverse events of intralesional pentavalent antimonials in the treatment of cutaneous leishmaniasis.

Int J Parasitol Drugs Drug Resist 2020 12 19;14:257-263. Epub 2020 Nov 19.

University Hospital of Brasília, Dermatology Department, SGAN 605, Asa Norte, Brasília-DF, 70840-901, Brazil; Postgraduate in Medical Sciences, Medical College, University of Brasília, UnB - Darcy Ribeiro University Campus, Asa Norte, Brasília-DF, 70.910-900, Brazil; Dermatomycology Laboratory, Medical College, University of Brasília, UnB - Darcy Ribeiro University Campus, Asa Norte, Brasília-DF, 70.910-900, Brazil; Postgraduate in Health Sciences, Health Sciences College, University of Brasília, UnB - Darcy Ribeiro University Campus, Asa Norte, Brasília-DF, 70.910-900, Brazil.

Introduction: The standard therapy for American cutaneous leishmaniasis (ACL) is intravenous meglumine antimoniate (IV-MA). However, treatment interruptions due to adverse events (AEs) and non-adherence are frequent. Consequently, intralesional MA (IL-MA) was proposed.

Objective: This study examined the effectiveness of and AEs associated with IL-MA.

Methods: We performed a retrospective cohort study of 240 patients with ACL. We excluded patients with mucous lesions and disseminated leishmaniasis and those who received treatment in the previous 6 months. We considered protocol treatments as the main risk factors. IL-MA was performed using a subcutaneous injection of MA in a volume sufficient to elevate the lesion base (approximately 1 mL/cm of lesion area) once weekly for 1-8 weeks. IV-MA was performed via intravenous injections of MA at a dosage of 10-20 mg Sb/kg/day for 20 days. The primary outcome was defined as a lesion cure 3 months after treatment, and AEs were secondary outcomes.

Results: Seventy-three patients were included. The IL-MA group consisted of 21 patients, and the IV-MA group consisted of 52 patients. The IL-MA group was older, had more comorbidities and more previous unsuccessful treatment of ACL. The antimonial dose was significantly lower in this group. The cure rate for IL-MA was 66.7%, which was lower than that in the IV-MA group (relative risk (RR) = 0.68, 95% CI: 0.50-0.92, p < 0.001), while the rate of AEs was similar. Female sex (RR = 1.16, 95% CI: 1.02-1.33), lesion diameter ≤1 cm (RR = 1.25, 95% CI: 1.00-1.56) and treatment with IV-MA (RR = 1.43, 95% CI: 1.06-1.93) were independently associated with achieving a cure. Comorbidities (RR = 1.7, 95% CI: 1.06-2.98) were independently associated with AEs.

Conclusions: Patients of IL-MA group were older, had more comorbidities and more previous unsuccessful treatment of ACL. Nevertheless, IL-MA had a cure rate of 66.7%, and it was useful in this context. A prospective randomized trial is recommended.
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http://dx.doi.org/10.1016/j.ijpddr.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723996PMC
December 2020

The challenge of concomitant infections in the coronavirus disease 2019 pandemic era: Severe acute respiratory syndrome coronavirus 2 infection in a patient with chronic Chagas disease and dimorphic leprosy.

Rev Soc Bras Med Trop 2020 6;53:e20200504. Epub 2020 Nov 6.

Hospital Universitário de Brasília, Serviço de Dermatologia, Brasília, DF, Brasil.

Coronavirus disease 2019 (COVID-19) was first officially described in Brazil on February 26th, 2020. The accumulation of reports of concomitant infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and pathogens that cause diseases endemic to tropical countries, such as dengue and chikungunya fever, has started to draw attention. Chagas disease and leprosy remain public health problems in many developing countries, such as Brazil. In this manuscript, we describe a case of concomitant leprosy, Chagas disease, and COVID-19, highlighting the cutaneous manifestations of SARS-CoV-2 infection and the clinical behavior of household contacts who previously received prophylactic Bacillus Calmette-Guérin vaccines.
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http://dx.doi.org/10.1590/0037-8682-0504-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670735PMC
November 2020

The interference of polypharmacy and the importance of clinical pharmacy advice in the treatment of leprosy: a case-control study.

Rev Soc Bras Med Trop 2020 1;53:e20200114. Epub 2020 Jun 1.

Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, DF, Brasil.

Introduction: Although supervised doses are essential for reducing leprosy treatment failure, the impact of specific drug interactions has rarely been assessed. This study aimed to estimate the risk of leprosy treatment suspension in patients receiving polypharmacy. METHODS We performed this case-control study in which the primary outcome was defined as the need to discontinue multibacillary leprosy treatment for at least one supervised dose, and the main risk factor was the detection of polypharmacy. Multivariate analysis by logistic regression was used for calculating odds ratio (OR).

Results: This study included 103 patients, of whom 43 needed to discontinue leprosy treatment (hemolysis = 26, hepatitis = 2, hemolysis associated with hepatitis = 6, and suspected treatment resistance = 9) and the rest did not. The severity of drug interactions had no effect on treatment discontinuation. Patients who used five or more drugs in addition to leprosy treatment had almost a 4-fold greater risk of treatment suspension (OR, 3.88; 95% confidence interval: 1.79-9.12; p < 0.001). The number of drugs used also positively influenced the occurrence of hemolysis (p < 0.001). No patient presented evidence of molecular resistance to rifampicin, dapsone, or ofloxacin treatment, as evidenced by genetic sequencing detection of rpoB, folp1, and gyrA mutations.

Conclusions: Polypharmacy has deleterious effects on the already difficult-to-adhere-to treatment of leprosy and polypharmacy induces hemolysis. Additional measures must be taken to avoid the undesirable effects of inadequate polypharmacy.
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http://dx.doi.org/10.1590/0037-8682-0114-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269535PMC
June 2020

A comprehensive systematic review of leishmaniasis in patients undergoing drug-induced immunosuppression for the treatment of dermatological, rheumatological and gastroenterological diseases.

Rev Inst Med Trop Sao Paulo 2020 11;62:e28. Epub 2020 May 11.

Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, Brazil

Immunosuppression is an important risk factor for leishmaniasis. We assessed the clinical profile, geographic distribution and prevalence of leishmaniasis in patients undergoing immunosuppressive therapy for dermatological, rheumatological or gastroenterological autoimmune diseases. We identified relevant studies in PubMed, EMBASE, Scopus, Web of Science and LILACS on July 3rd, 2018. We included articles that reported at least one case of leishmaniasis in patients undergoing immunosuppressive treatment for dermatological, rheumatological or gastroenterological diseases. Our protocol was registered in PROSPERO (CRD42018103050). We assessed the quality of the included studies with the Joanna Briggs Institute Critical Appraisal Tool. After the removal of duplicates, 5,431 articles were collected and screened. We included 138 articles; the prevalence of leishmaniasis in six methodologically similar studies varied from three to 1,282 cases per 100,000 patients using anti-TNFα drugs, but the results were significantly heterogeneous . Leishmaniasis in patients treated with immunosuppressive drugs is a health problem mostly reported in European countries bordering the Mediterranean Sea; sporadic activities, such as travelling, seem not to be associated with a significant risk of leishmaniasis, although effective control measures must always be observed.
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http://dx.doi.org/10.1590/s1678-9946202062028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232954PMC
May 2020

The accuracy of the Montenegro skin test for leishmaniasis in PCR-negative patients.

Rev Soc Bras Med Trop 2020 27;53:e20190433. Epub 2020 Apr 27.

Núcleo de Medicina Tropical, Universidade de Brasília, Brasília, DF, Brasil.

Introduction: As highly specific molecular biology-based techniques may not be sensitive enough for the diagnosis of American tegumentary leishmaniasis (ATL), clinicians frequently rely on immunological tests before treatment initiation. Hence, the correct combination of diagnostic tests is imperative for ATL diagnosis. We aimed to evaluate the accuracy of the Montenegro (Leishmanin) skin test (MST) in polymerase chain reaction (PCR)-negative patients to accurately detect ATL.

Methods: Patients with a clinical picture compatible with ATL were divided into ATL (confirmed by lesion smear, culture indirect immunofluorescence, and/or histopathology) and no-ATL (diseases that can mimic leishmaniasis) groups. Conventional PCR for the minicircle kDNA of Leishmania was performed, and the MST was carried out for PCR-negative patients.

Results: Ninety-nine patients were included in this study, including 79 diagnosed with ATL (6 with mucocutaneous leishmaniasis) and 20 without ATL (no-ATL group). The MST showed a high sensitivity of 90.0% (95% confidence interval [CI] = 69.90-97.21) in PCR-negative patients that was 10% higher than the sensitivity reported in PCR-positive population (79.66%; 95% CI = 67.73-87.96).

Conclusions: One of the most important reasons for PCR negativity among patients with active ATL is the presence of a strong cellular immunological response, especially in chronic and mucocutaneous leishmaniasis. This reinforces the considerable utility of the tests that detect cellular responses against Leishmania antigens such as the MST in PCR-negative patients when the performance in screening situations is questionable.
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http://dx.doi.org/10.1590/0037-8682-0433-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198066PMC
May 2020
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