Pathological findings and morphologic correlation of the lungs of autopsied patients with SARS-CoV-2 infection in the Brazilian Amazon using transmission electron microscopy

Abstract INTRODUCTION: Electron microscopy (EM) is a rapid and effective tool that can be used to create images of a whole spectrum of virus-host interactions and, as such, has long been used in the discovery and description of viral mechanisms. METHODS: Electron microscopy was used to evaluate the pulmonary pathologies of postmortem lung sections from three patients who died from infection with SARS-associated coronavirus 2 (SARS-CoV-2), a new member of the Coronaviridae family. RESULTS: Diffuse alveolar damage (DAD) was predominant in all three patients. The early exudative stage was characterized principally by edema and extravasation of red blood cells into the alveolar space with injury to the alveolar epithelial cells; this was followed by detachment, apoptosis, and necrosis of type I and II pneumocytes. The capillaries exhibited congestion, exposure of the basement membrane from denuded endothelial cells, platelet adhesion, fibrin thrombi, and rupture of the capillary walls. The proliferative stage was characterized by pronounced proliferation of type II alveolar pneumocytes and multinucleated giant cells. The cytopathic effect of SARS-CoV-2 was observed both in degenerated type II pneumocytes and freely circulating in the alveoli, with components from virions, macrophages, lymphocytes, and cellular debris. CONCLUSIONS: Viral particles consistent with the characteristics of SARS-CoV-2 were observed mainly in degenerated pneumocytes, in the endothelium, or freely circulating in the alveoli. In the final stage of illness, the alveolar spaces were replaced by fibrosis.

Das salas de autopsias e microscopias para a vida: mentoria informal em um programa de residência médica de patologia / From autopsy rooms and microscopes to life: informal mentoring in a pathology medical residency program

Resumo: Introdução: Além de demorada, a mentoria em Medicina ocorre em vários níveis e é complexa, pois pode incluir várias combinações de ensino, prática clínica, atendimento ao paciente e pesquisa. Relato de experiência: Trata-se de um relato de experiência individual de uma mentorada em um programa de residência médica em patologia do Hospital Universitário Getúlio Vargas, de Manaus, no Amazonas. Descrevem-se os benefícios individuais e coletivos de uma mentoria fora de um programa formal, orientada pelo discernimento e pela maturidade de relacionamento entre mentor e mentorada. Discussão: Discentes de programa de residência médica podem se beneficiar sobremaneira, pessoal e profissionalmente, de mentorias bem conduzidas. Conclusão: No relacionamento de mentoria, são imprescindíveis qualidades como respeito mútuo, discernimento e abnegação, para que o mentorado cresça e desenvolva uma identidade profissional independente, ainda que atrelada à relação de mentoria, e amadurecida, em seu pleno desenvolvimento, a fim de que ele seja um novo mentor e novos alunos sejam beneficiados.

Abstract: Introduction: Mentoring in medicine is time-consuming on several levels and complex, as it can include various combinations of teaching, clinical practice, patient care, and research. Experience report: This report is on the individual experience of a mentee in a medical residency program in Pathology at the Getúlio Vargas University Hospital (Manaus-AM). The individual and collective benefits of mentoring outside a formal program are described, guided by the discernment and maturity of the relationship between mentor and mentee. Discussion: Medical residency program students can benefit greatly, both personally and professionally, from well-conducted mentoring. Conclusion: In the mentoring relationship, qualities such as mutual respect, discernment, and selflessness are essential so that the mentee grows and develops a fully developed and independent professional identity, albeit bound to the mentoring relationship, in order for him become a new mentor and to benefit new students.

Histopathological changes in epithelium of hair follicles and acrosyringium caused by measles in child

Abstract Some epidermal alterations in measles has been described, such as keratinocytes apoptotic, parakeratosis, giant-cell formation, intranuclear and cytoplasmic inclusions, dyskeratosis, spongiosis, and intracellular edema. The authors report for the first time in human a case of measles with the presence of multinucleated giant cells in the hair follicle and dyskeratosis in acrosyringium.

Diabetes insipidus secondary to tuberculous meningoencephalitis with hypothalamic involvement extending to the hypophysis: a case report

Abstract The involvement of Mycobacterium tuberculosis in the central nervous system (CNS) is an uncommon and devastating manifestation of tuberculosis. We report a case of disseminated tuberculosis presenting as meningoencephalitis, hypothalamic involvement with extension to the hypophysis, and secondary insipidus diabetes diagnosed at autopsy.

Hallux amputation after a freshwater stingray injury in the Brazilian Amazon

Abstract: Freshwater stingray injuries are a common problem in the Brazilian Amazon, affecting mostly riverine and indigenous populations. These injuries cause severe local and regional pain, swelling and erythema, as well as complications, such as local necrosis and bacterial infection. Herein, we report a case of bacterial infection and hallux necrosis, after a freshwater stingray injury in the Brazilian Amazon, which eventually required amputation. Different antimicrobial regimens were administered at different stages of the disease; however, avoiding amputation through effective treatment was not achieved.

Snakebites as a largely neglected problem in the Brazilian Amazon: highlights of the epidemiological trends in the State of Amazonas

Envenoming snakebites are thought to be a particularly important threat to public health worldwide, especially in rural areas of tropical and subtropical countries. The true magnitude of the public health threat posed by snakebites is unknown, making it difficult for public health officials to optimize prevention and treatment. The objective of this work was to conduct a systematic review of the literature to gather data on snakebite epidemiology in the Amazon region and describe a case series of snakebites from epidemiological surveillance in the State of Amazonas (1974-2012). Only 11 articles regarding snakebites were found. In the State of Amazonas, information regarding incidents involving snakes is scarce. Historical trends show an increasing number of cases after the second half of the 1980s. Snakebites predominated among adults (20-39 years old; 38%), in the male gender (78.9%) and in those living in rural areas (85.6%). The predominant snake envenomation type was bothropic. The incidence reported by the epidemiological surveillance in the State of Amazonas, reaching up to 200 cases/100,000 inhabitants in some areas, is among the highest annual snakebite incidence rates of any region in the world. The majority of the cases were reported in the rainy season with a case-fatality rate of 0.6%. Snakebite envenomation is a great disease burden in the State of Amazonas, representing a challenge for future investigations, including approaches to estimating incidence under-notification and case-fatality rates as well as the factors related to severity and disabilities.

Poorly differentiated synovial sarcoma in the wrist - Case report

Synovial sarcomas are rare malignant tumors affecting mainly young adults, presenting as a slow growth mass located in deep soft tissues of extremities, near the joints. In this report a 34-year-old male patient, presented an ulcerovegetative lesion on the right wrist which was completely excised. Histopathology and immunohistochemistry confirmed synovial sarcomas with poorly differentiated cells. This patient presented 11 months later with ipsilateral axillary lymph node metastasis, which emphasizes the unfavorable prognosis of this synovial sarcoma variant. The indolent growth pattern of this sarcoma justifies the well circumscribed initial stages, which progressively infiltrate adjacent structures with lung metastasis (80%) and lymph node involvement (20%) and thus corroborates the importance of early diagnosis and proper treatment.

Acurácia dos exames citológicos cervicovaginais em Estado de elevada incidência de câncer de colo de útero / Validity of cervicovaginal cytology in a Brazilian State with high incidence rate of cervical cancer

OBJETIVO: Avaliar a acurácia da citologia cervicovaginal realizada no principal laboratório do Estado de Roraima, por concordância entre avaliadores (monitoramento externo) e com resultados histopatológicos. MÉTODOS: Lâminas de 100 mulheres, de uma amostra de conveniência de base populacional, foram avaliadas pelo LAPER, principal laboratório de referência do Sistema Único de Saúde do Estado de Roraima e reavaliadas por médicos patologistas experts externos ao laboratório. Foram avaliados índice Kappa, sensibilidade e especificidade. O estudo foi aprovado pela Coordenação do Laboratório Estadual e pelo Comitê de Ética em Pesquisa da Universidade Federal de Roraima. RESULTADOS: Quanto à prevalência de atipias celulares (relacionadas ao papilomavírus humano), não houve concordância entre resultados emitidos pelo LAPER e pelos patologistas externos (k=0,21). Constatou-se baixa sensibilidade (28,5%) e especificidade de 89,2% para o desempenho do LAPER, com elevada proporção de resultados falsos positivos e falsos negativos. Os laudos citológicos de patologistas externos apresentaram sensibilidade e especificidade maiores (71,4 e 98,9%, respectivamente), descartando que erros de coleta e coloração possam explicar o baixo desempenho do LAPER. CONCLUSÃO: O baixo desempenho diagnóstico da citologia cervicovaginal pode ser uma barreira para o controle do câncer de colo de útero em Roraima. Ressalta-se a necessidade de capacitação profissional e monitoramento interno e externo em Estados brasileiros com alta incidência de câncer de colo de útero. .

PURPOSE: To evaluate the validity of cervicovaginal cytology performed at LAPER, the main Laboratory of Pathology of the State of Roraima, Brazil, by interrater agreement (external monitoring) and agreement with histopathologic results. METHODS: One hundred women were included, a population-based convenience sample. Their cervical cytological exams were evaluated by the laboratory staff and reviewed by expert medical pathologists, external to the laboratory. Cohen's Kappa index, sensitivity and specificity were evaluated. The study was approved by LAPER coordination and Federal University of Roraima Research Ethics Commitee. RESULTS: Regarding the prevalence of human papillomavirus-related atypical, there was no concordance between the results issued by LAPER and by the external pathologists (k=0.21). A low sensitivity (28.5%) and specificity (89,2%) was detected for the diagnostic performance of LAPER, with a high proportion of false positive and false negative results. The cytological reports of the external pathologists showed higher sensitivity and specificity (71.4 and 98.9%, respectively), ruling out the possibility that errors related to collection methods and staining would explain the low performance of the laboratory. CONCLUSION: A low diagnostic accuracy of cervicovaginal cytology can be a barrier against the control of cervical cancer in Roraima. We emphasize the need for professional training and internal and external monitoring in Brazilian states with a high incidence of cervical cancer. .

Chlamydia trachomatis in human immunodeficiency virus-infected men treated at a referral hospital for sexually transmitted diseases in the Amazonas, Brazil

OBJECTIVES: The aim of the present study was to determine the Chlamydia trachomatis prevalence and to identify the demographic, behavioural and clinical factors associated with C. trachomatis in human immunodeficiency virus infected men. STUDY: This was a cross-sectional study of C. trachomatis prevalence among human immunodeficiency virus-infected men enrolled at the Outpatient clinic of acquired immunodeficiency syndrome of the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado in Manaus, Amazonas, Brazil. C. trachomatis deoxyribonucleic acid from urethral samples was purified and submitted to real time polymerase chain reaction to identify the presence of C. trachomatis. RESULTS: A total of 276 human immunodeficiency virus-infected men were included in the study. The prevalence of C. trachomatis infection was 12% (95% confidence interval 8.1%-15.7%). The mean age of the participants was 34.63 (standard deviation 10.80) years. Of the 276 human immunodeficiency virus-infected men, 93 (56.2%) had more than one sexual partner in the past year and 105 (38.0%) reported having their first sexual intercourse under the age of 15 years. Men having sex with men and bisexuals amounted to 61.2% of the studied population. A total of 71.7% had received human immunodeficiency virus diagnosis in the last three years and 55.1% were using antiretroviral therapy. Factors associated with C. trachomatis infection in the logistic model were being single (p<0.034), men having sex with men (p<0.021), and having previous sexually transmitted diseases (p<0.001). CONCLUSION: The high prevalence of C. trachomatis infection among human immunodeficiency virus-infected men highlights that screening human immunodeficiency virus-infected men for C. trachomatis, especially among men having sex with men, is paramount to control the spread of C. trachomatis infection. .

Syphilis in pregnancy and congenital syphilis in Amazonas State, Brazil: an evaluation using database linkage / Sífilis em gestantes e sífilis congênita no Estado do Amazonas, Brasil: uma abordagem por meio de relacionamento de bases de dados / Sífilis en mujeres embarazadas y sífilis congénita en el estado de Amazonas, Brasil: una aproximación a través de la relación en bases de datos

This study analyzes notification of syphilis in pregnancy and congenital syphilis in Amazo- nas State, Brazil, from 2007 to 2009 and verifies underreporting in databases in the National Information System on Diseases of Notification (SINAN) and the occurrence of perinatal deaths associated with congenital syphilis and not reported in the Mortality Information System (SIM). This was a cross-sectional study with probabilistic record linkage between the SINAN and SIM. There were 666 reports of syphilis in pregnant women, including 224 in 2007 (3.8/1,000), 244(4.5/1,000) in 2008, and 198(4.0/1,000) in 2009. The study found 486 cases of congenital syphilis, of which 153 in 2007 (2.1/1,000), 193 in 2008 (2.6/1,000), and 140 in 2009 (2.0/1,000). After linkage of the SINAN databases, 237 pregnant women (35.6%) had cases of congenital syphilis reported. The SIM recorded 4,905 perinatal deaths, of which 57.8% were stillbirths. Probabilistic record linkage between SIM and SINAN-Congenital Syphilis yielded 13 matched records. The use of SINAN and SIM may not reflect the total magnitude of syphilis, but provide the basis for monitoring and analyzing this health problem, with a view towards planning and management.

O estudo descreve o perfil das notificações de sífilis em gestantes e sífilis congênita no Estado do Amazonas, Brasil, entre 2007 e 2009, e verifica a subnotificação em bases de dados do Sistema Nacional de Agravos de Notificação (SINAN) e a ocorrência de óbitos perinatais associados à sífilis congênita não notificados no Sistema de Informação de Mortalidade (SIM). Estudo seccional com relacionamento entre SINAN e SIM. Ocorreram 666 notificações de sífilis em gestantes, sendo 224 em 2007 (taxa detecção de 3,8/1.000 nascidos vivos); 244 (4,5/1.000) em 2008 e 198 (4,0/1.000) em 2009. Encontraram-se 486 casos de sífilis congênita, sendo 153 (incidência: 2,1/1.000) em 2007, 193 (2,6/1.000) em 2008 e 140 (2,0/1.000) em 2009. Após o relacionamento das bases-SINAN, 237 (35,6%) gestantes tinham casos de sífilis congênita notificados. No SIM, constavam 4.905 óbitos perinatais, sendo 57,8% fetais. No relacionamento do SIM/SINAN-sífilis congênita foram encontrados 13 registros pareados. A utilização do SINAN e SIM podem não refletir a total magnitude da sífilis, mas formam base para o monitoramento e análise da situação de saúde, tendo em vista o planejamento e a gestão.

El estudio describe el perfil de las notificaciones de sífilis en mujeres embarazadas y sífilis congénita en la Amazonía entre 2007 y 2009, analizando el sub-registro en las bases de datos del Sistema Nacional de Enfermedades de Declaración Obligatoria (SINAN) y la ocurrencia de muertes perinatales, asociadas con sífilis congénita no declarada el Sistema de Información sobre la Mortalidad (SIM). Se trata de un estudio transversal de relación entre SINAN y SIM. Hubo 666 notificaciones de sífilis en mujeres embarazadas, y 224 en 2007 (tasa de detección de 3,8/1.000 nacidos vivos), 244 (4,5/1.000) en 2008 y 198 (4,0/1.000) en 2009. Así como 486 casos de sífilis congénita, 153 (incidencia: 2,1/1.000) en 2007, 193 (2,6/1.000) en 2008 y 140 (2,0/1.000) en 2009. Después de registrar la vinculación –SINAN, 237 (35,6%) mujeres habían reportado casos de sífilis congénita. Estaba presente en 4.905 de muertes perinatales, y en un 57,8% del feto. Se determinó la asociación de SIM/SINAN sífilis congénita –en 13 registros coincidentes. El uso de SIM SINAN puede no reflejar toda la magnitud de la sífilis, pero constituye la base para el seguimiento y análisis de la situación de salud, con vistas a la planificación y gestión.

Cost-effectiveness of the vaccine against human papillomavirus in the brazilian Amazon region / Custo-efetividade da vacina contra o papilomavírus humano na região Amazônica brasileira

OBJECTIVE: To assess the cost-utility of the human papillomavirus (HPV) vaccination on the prevention of cervical cancer in the Brazilian Amazon region. METHODS: AMarkov cohort modelwas developed to simulate the natural evolution of HPV and its progress to cervical cancer, considering the current preventive programs and treatment costs. The one-year transition probabilities were mainly based on empirical data of local and national studies. The model evaluated the addition of the vaccine to three cervical cancer-screening scenarios (0, 3 or 10 exams throughout life). RESULTS: The scenario of three Pap tests resulted in satisfactory calibration (base case). The addition of HPV vaccination would reduce by 35% the incidence of cervical cancer (70% vaccination coverage). The incremental cost-effectiveness ratio was US$ 825 for each quality-adjusted life year gained. The sensitivity analysis confirms the robustness of this result, and duration of immunity was the parameter with greater variation in incremental cost-effectiveness ratio. CONCLUSION: Vaccination has a favorable profile in terms of cost-utility, and its inclusion in the immunization schedule would result in a substantial reduction in incidence and mortality of invasive cervical cancer in the Brazilian Amazon region.

OBJETIVO: Avaliar a custo-efetividade da vacinação contra o papilomavírus humano (HPV) na prevenção do câncer de colo de útero na região Amazônica brasileira. MÉTODOS: Um modelo de coorte Markov foi desenvolvido para simular a história natural do HPV e seu progresso para câncer de colo de útero, considerando os atuais programas de prevenção e os custos de tratamento. As probabilidades de um ano de transição foram baseadas principalmente em dados empíricos de estudos locais e nacionais. O modelo avaliou a adição da vacina a três cenários de rastreio de câncer de colo de útero (0, 3 ou 10 exames ao longo da vida). RESULTADOS: O cenário de três exames de Papanicolau resultou em calibração satisfatória (caso base). A adição de vacinação contra o HPV reduziria em 35% a incidência de câncer de colo de útero (70% de cobertura de vacinação). A razão incremental de custo-efetividade foi US$ 825 para cada ano de vida ajustado para qualidade ganho. A análise de sensibilidade confirma a robustez deste resultado, e a duração de imunidade foi o parâmetro com maior variação na razão incremental de custo-efetividade. CONCLUSÃO A vacinação tem um perfil favorável em termos de custo-utilidade, e sua inclusão no calendário de imunização resultaria em redução substancial de incidência e de mortalidade relacionadas ao câncer de colo de útero na região Amazônica brasileira.

Biological behavior of Trypanosoma cruzi stocks obtained from the state of Amazonas, Western Brazilian Amazon, in mice / Comportamento biológico de isolados de Trypanosoma cruzi obtidos no estado do Amazonas, Amazônia Ocidental Brasileira, em camundongos

INTRODUCTION: The biological diversity of circulating Trypanosoma cruzi stocks in the Amazon region most likely plays an important role in the peculiar clinic-epidemiological features of Chagas disease in this area. METHODS: Seven stocks of T. cruzi were recently isolated in the State of Amazonas, Brazil, from humans, wild mammals, and triatomines. They belonged to the TcI and Z3 genotypes and were biologically characterized in Swiss mice. Parasitological and histopathological parameters were determined. RESULTS: Four stocks did not promote patent parasitemia in mice. Three stocks produced low parasitemia, long pre-patent periods, and a patent period of 1 day or oscillating parasitemia. Maximum parasitemia ranged from 1,400 to 2,800 trypomastigotes/0.1mL blood. Mice inoculated with the T. cruzi stocks studied showed low positivity during fresh blood examinations, ranging from 0% to 28.6%. In hemoculture, positivity ranged from 0% to 100%. Heart tissue parasitism was observed in mice inoculated with stocks AM49 and AM61. Stock AM49 triggered a moderate inflammatory process in heart tissue. A mild inflammatory process was observed in heart tissue for stocks AM28, AM38, AM61, and AM69. An inflammatory process was frequently observed in skeletal muscle. Examinations of brain tissue revealed inflammatory foci and gliosis in mice inoculated with stock AM49. CONCLUSIONS: Biological and histopathological characterization allowed us to demonstrate the low infectivity and virulence of T. cruzi stocks isolated from the State of Amazonas.

INTRODUÇÃO: A diversidade biológica dos estoques Trypanosoma cruzi circulantes na Região Amazônica pode desempenhar importante papel nas características clínico-epidemiológicas peculiares da doença de Chagas nesta área. MÉTODOS: Sete isolados de T. cruzi do Estado do Amazonas provenientes de humanos, mamíferos silvestres e triatomíneos, pertencentes aos genótipos TcI e Z3, foram biologicamente caracterizados em camundongos Swiss. Foram avaliados parâmetros parasitológicos e histopatológicos. RESULTADOS: Quatro isolados não produziram parasitemia patente em camundongos. Três isolados promoveram baixa parasitemia com longos períodos pré-patentes, período patente de um dia ou parasitemia oscilante. A parasitemia máxima variou de 1.400 a 2.800 tripomastigotas/0,1mL de sangue. Os camundongos inoculados com os isolados estudados mostraram baixa positividade no exame a fresco, variando de 0 a 28,6%. Para a hemocultura, a positividade variou de 0 a 100%. Parasitismo cardíaco foi observado em camundongos inoculados com os isolados AM49 e AM61. O isolado AM49 produziu inflamação moderada no tecido cardíaco. Processo inflamatório discreto foi observado no tecido cardíaco de camundongos inoculados com os isolados AM28, AM38, AM61 e AM69. Processo inflamatório em músculo esquelético foi muito frequente. O exame do tecido cerebral revelou focos inflamatórios e gliose em camundongos inoculados com o isolado AM49. CONCLUSÕES: A caracterização biológica e histopatológica demonstrou baixa infecciosidade e virulência dos estoques de T. cruzi isolados no Estado do Amazonas.

Coinfection of Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human papillomavirus and anal intraepithelial neoplasia in HIV patients in Amazon, Brazil

OBJECTIVE: The prevention of anal cancer is a goal of worldwide Aids support centers. Despite the efforts that have been made and progress in the antiretroviral therapy, effective disease control remains elusive. Difficulty in preventing anal cancer may result from the ineffectiveness of highly active antiretroviral therapy on the human papillomavirus (HPV) since the coinfection with HIV and HPV appears to increase the risk of HPV-infected cells, becoming cancerous. METHODS: We evaluated 69 HIV-positive and 30 HIV-negative male patients who underwent cytological evaluation by RT-PCR for the presence of HPV, Epstein-Barr virus, cytomegalovirus and herpes virus types (HSV) 1 and 2, and histopathology analysis of the anal canal. RESULTS: The prevalence of anal intraepithelial neoplasia was 35% and it was restricted to HIV-positive patients. Patients infected with high-risk HPV and with fewer than 50 TCD4 cells/µL showed an anal intraepithelial neoplasia rate of 85.7% compared to those with TCD4 cells > 200 cells/µL (p<0.01). The rate of viral coinfection was 16.9% of the sexual transmitted diseases cases and it was correlated with HIV-1 viral load of more than 10.001 copies/mL (p=0.017). The rate of AIN in coinfected patients was 36.4% (p=0.047). CONCLUSIONS: In this study, at the main institution for the treatment of HIV/AIDS in the Amazon region of Brazil, anal coinfection with HPV, cytomegalovirus, HSV-1, HSV-2 and Epstein-Barr virus occurred only in HIV-positive patients and it was directly influenced by the viral load of HIV-1. In this study, anal viral coinfection showed no additional risk for the development of anal intraepithelial neoplasia. (AU)

OBJETIVO: A prevenção do câncer anal tem sido aplicada pelos centros de apoio a pacientes com Aids em todo o mundo. Apesar dos esforços empregados, o eficaz controle da doença permanece distante. A dificuldade na prevenção do câncer anal pode resultar, em parte, da ineficácia da ação da terapia antirretroviral sobre o papilomavírus humano (HPV), pois a coinfecção com HIV e HPV parece aumentar o risco das células infectadas pelo HPV em tornarem-se cancerosas. MÉTODOS: Foram avaliados 69 HIV-positivos e 30 pacientes HIV-negativos do sexo masculino, que foram submetidos à avaliação citológica anal por real time-PCR para a presença de HPV, vírus Epstein-Barr, citomegalovírus e herpes vírus tipos (HSV) 1 e 2 além da análise histopatológica de fragmento de mucosa do canal anal. RESULTADOS: A prevalência de neoplasia intraepitelial anal foi de 35% e foi restrita a pacientes HIV-positivos. Os pacientes infectados com o HPV de alto risco e com contagem inferior a 50 células TCD4/µL mostraram taxa de neoplasia intraepitelial anal de 85,7%. A diferença foi significativa quando comparado a pacientes com células TCD4 > 200 células/µL (p<0,01). A taxa de coinfecção viral foi de 16,9% dos casos de doenças sexualmente transmissíveis e diretamente correlacionada à carga viral HIV-1 superior a 10,001 cópias/mL (p=0,017). A taxa de neoplasia intraepitelial anal em pacientes coinfectados foi de 36,4% (p=0,047). CONCLUSÕES: Neste estudo, realizado na principal instituição para o tratamento de HIV/Aids na região amazônica do Brasil, a coinfecção anal com HPV, citomegalovírus, HSV-1, HSV-2 e vírus Epstein-Barr ocorreu somente em pacientes HIV-positivos e foi influenciada pela carga viral do HIV-1. Neste estudo, a coinfecção viral anal não representou risco adicional ao desenvolvimento da neoplasia intraepitelial anal. (AU)

Assessment of completion of forms requesting skin biopsies / Avaliação do preenchimento de solicitações de biópsias da pele

BACKGROUND: Information contained in request forms for histopathological examinations is essential for interpreting tissue changes observed in microscopy. OBJECTIVE: To determine the adequacy of information provided on forms requesting skin biopsies. METHOD: Assessment, in two health institutions, of 647 forms requesting skin biopsies in order to determine the completeness on the forms of the clinical details/items considered necessary for undertaking skin biopsies. RESULTS: Of the total 18 items on the forms, 7 were found to relay complete information in under 10% of the forms and only 9 items were correctly completed in over 80% of the requests. CONCLUSION: We concluded that information on many of the essential items required for a correct interpretation of the anatomopathologic examination was missing from the request forms.

FUNDAMENTOS: As informações contidas nas requisições de exames histopatológicos são fundamentais para a interpretação das alterações teciduais observadas na microscopia. OBJETIVO: Verificar a frequência do preenchimento de itens de requisições de biópsias da pele. MÉTODO: Avaliação do preenchimento de 647 solicitações de biópsias de pele, em duas instituições de saúde, em relação aos itens considerados necessários. RESULTADOS: De um total de 18 itens avaliados, 7 foram preenchidos em menos de 10% das requisições e 9 foram preenchidos corretamente em mais de 80% das requisições. CONCLUSÃO: Verificou-se uma insuficiência do preenchimento de itens fundamentais para uma interpretação adequada do exame anatomopatológico.

Morphometric analysis of dendritic cells from anal mucosa of HIV-positive patients and the relation to intraepithelial lesions and cancer seen at a tertiary health institution in Brazil / Análise morfométrica das células dendríticas da mucosa anal de pacientes HIV-positivos e relação com as lesões intraepiteliais e o câncer numa instituição de saúde terciária no Brasil

PURPOSE: To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells. METHODS: A prospective study was performed to morphometrically analyze the relative volume of the dendritic cells and the relationship between anal intraepithelial neoplasia and cancer in HIV-positive patients from the Tropical Medicine Foundation of Amazonas, Brazil. All patients were submitted to biopsies of anorectal mucosa to perform a classic histopathological and immunohistochemical analysis, employing antibodies against CD1a and DC-SIGN for the morphometric quantification of dendritic cells. RESULTS: HIV-negative patients displayed a CD1a DC density significantly higher than that of HIV-positives patients (3.75 versus 2.54) (p=0.018), and in patients with severe anal intraepithelial neoplasia had correlated between DC CD1a density with levels of CD4 + cells (p: 0.04) as well as the viral load of HIV-1 (p: 0.035). A not significant rise in the median density of CD1a+ DC was observed in the HIV positive/ HAART positive subgroup compared to the HIV positive/ HAART negative subgroup. The CD1a+ DC were also significantly increased in HIV-negative patients with anorectal condyloma (2.33 to 3.53; p=0.05), with an opposite effect in HIV-positive patients. CONCLUSIONS: Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1. Our study describes for the first time the density of subepithelial DC-SIGN+ dendritic cells in patients with anal severe anal intraepithelial neoplasia and points to the possibility that a specific therapy for HIV induces the recovery of the density of epithelial DC.

OBJETIVO: Quantificar morfometricamente as células dendríticas DC CD1a+ e DC DC-SIGN+ em pacientes HIV positivos portadores de neoplasia escamosa intraepitelial anal e avaliar os efeitos da infecção pelo HIV, da terapia antirretroviral e da infecção pelo HPV sobre as células dendríticas epiteliais e subepiteliais. MÉTODOS: Um estudo prospectivo foi realizado para analisar morfometricamente o volume relativo das células dendríticas e as relações entre neoplasia intraepitelial anal e o câncer em pacientes HIV positivos da Fundação de Medicina Tropical do Amazonas, Brasil.Todos os pacientes foram submetidos a biópsia da mucosa retal para realizar uma análise clássica histopatológica e imunohistoquímica utilizando anticorpos contra anti-CD1a e anti-DC-SIGN, para a quantificação morfométrica das células dendríticas. RESULTADOS: Os pacientes HIV negativos apresentaram densidade das DC CD1a+ significativamente maior do que a dos pacientes HIV positivos (3,75 versus 2,54) (p:0,018), e os pacientes com severa apresentaram correlação das DC CD1a com os níveis de células TCD4(p:0,04) assim como a carga viral do HIV-1 (p:0,035). Observamos no subgrupo HIV-positivo/HAART positivo elevação não significativa na mediana da densidade das DC CD1a+ em relação ao grupo HIV-positivo/HAART negativo. As DC CD1a+ também se elevaram nos pacientes HIV negativo portadores de condiloma anorretal(2,33 para 3,53; p:0,05), com efeito inverso nos pacientes HIV positivos. CONCLUSÕES: Nossos dados confirmam a potencialização da ação sinérgica representada pela coinfecção HIV-HPV sobre o epitélio anal, fragilizando as DC em sua função primordial de vigilância imune. Notoriamente nos pacientes com neoplasia intraepithelial anal grave, a densidade das DC CD1a+ epiteliais sofreu influência da carga viral do HIV-1. Nosso estudo descreveu pela primeira vez a densidade das DC subepiteliais DC-SIGN+ em pacientes com neoplasia intraepithelial anal severa e apontamos para a possibilidade de que a terapia específica para o HIV induza a recuperação da densidade das DC epiteliais.

Estudo clínico randomizado comparando antimoniato de meglumina, pentamidina e anfotericina B para o tratamento da leishmaniose cutânea ocasionada por Leishmania guyanensis / A randomized clinical trial comparing meglumine antimoniate, pentamidine and amphotericin B for the treatment of cutaneous leishmaniasis by Leishmania guyanensis

FUNDAMENTOS: O tratamento da leishmaniose tegumentar americana (LTA) ainda constitui desafio, pois a maioria dos medicamentos é injetável e têm-se poucos ensaios clínicos randomizados comparando a eficácia das drogas. Além disso, é provável que as espécies de Leishmania tenham influência nas respostas terapêuticas. OBJETIVOS: Avaliar e comparar a eficácia e a segurança dos esquemas de tratamento na LTA, ocasionada por Leishmania (Viannia) guyanensis. MÉTODOS: 185 pacientes foram selecionados, conforme critérios de elegibilidade, e distribuídos, aleatoriamente, em 3 grupos - 2 com 74 enfermos e outro com 37 - que receberam, respectivamente, antimoniato de meglumina, isotionato de pentamidina e anfotericina B em doses, períodos e vias de administração padronizados. Os enfermos foram reexaminados um, dois e seis meses após o final dos tratamentos. RESULTADOS: Não houve diferença entre os grupos terapêuticos em relação ao sexo, idade, número ou local das lesões. A análise por intenção de tratar (ITT) mostrou eficácias de 58,1 por cento para a pentamidina e 55,5 por cento para o antimoniato (p=0,857). O grupo da anfotericina B foi analisado separadamente, pois 28 (75,7 por cento) pacientes negaram-se a continuar no estudo após a randomização. Eventos adversos leves ou moderados foram relatados por 74 (40 por cento) pacientes, principalmente artralgia (20,3 por cento), para o grupo do antimoniato, e dor (35,1 por cento) ou enduração (10,8 por cento) no local das injeções para a pentamidina. CONCLUSÕES: A pentamidina tem eficácia similar ao antimonial pentavalente para o tratamento da LTA ocasionada por L. guyanensis. Face aos baixos resultados de eficácia apresentados por ambas as drogas, necessita-se, com urgência, investigar novas opções terapêuticas para esta enfermidade.

FUNDAMENTALS: American tegumentary leishmaniasis (ATL) treatment remains a challenge, since most available drugs are injectable and only a small number of comparative, randomized clinical trials have been performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. OBJECTIVES: To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia) guyanensis. METHODS: 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment. RESULTS: No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT) analysis showed efficacy of 58.1 percent for pentamidine and 55.5 percent for meglumine (p=0.857). The amphotericin B group was analyzed separately, since 28 patients (75.7 percent) in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40 percent) patients, especially arthralgia (20.3 percent) in the meglumine group, and pain (35.1 percent) or induration (10.8 percent) at the site of injection in the pentamidine group. CONCLUSION: Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.

Mother-to-child transmission of HIV infection in Manaus, State of Amazonas, Brazil / Transmissão materno-infantil da infecção pelo HIV em Manaus, Amazonas, Brasil

INTRODUCTION: Reduction in the vertical transmission of HIV is possible when prophylactic measures are implemented. Our objective was to determine demographic characteristics of HIV-infected pregnant women and the rate of mother-to-child transmission of HIV in Manaus, Amazonas, Brazil. METHODS: A descriptive study was conducted using notification, and investigating data from the Notifiable Diseases Data System in the Brazilian State of Amazonas, between 2007 and 2009. RESULTS: During the study period, notification was received of 509 HIV-positive pregnant women. The vertical transmission was 9.9 percent (95 percent CI: 7.2-12.6 percent). The mean age of women was 27 years (SD: 5.7), and the majority (54.8 percent) had not completed elementary school (eighth grade). Diagnosis of HIV seropositivity was made prior to pregnancy in 115 (22.6 percent) women, during prenatal care in 302 (59.3 percent), during delivery in 70 (13.8 percent), and following delivery in 22 (4.3 percent). Four hundred four of these women (79.4 percent) had had prenatal care, with 79.4 percent of patients receiving antiretroviral during pregnancy and 61.9 percent of the newborn infants receiving prophylaxis. In the final multivariate logistic regression model, living in urban area [OR = 0.7 (95 percent CI: 0.35-0.89)] and having had prenatal care [OR = 0.1 (95 percent CI: 0.04-0.24)] remained as protective factors against vertical HIV transmission in this population. CONCLUSIONS: The relevance of adequate compliance with the measures already established as being effective in guaranteeing a reduction in HIV transmission within the maternal and infant population should be emphasized.

INTRODUÇÃO: A redução da transmissão vertical do HIV é possível quando medidas profiláticas são implementadas. Nosso objetivo foi determinar as características demográficas de gestantes soropositivas e a taxa de transmissão vertical do HIV em Manaus, Amazonas, Brasil. MÉTODOS: Estudo descritivo foi realizado usando dados de notificação e investigação do Sistema de Informações de Agravos de Notificações (SINAN) do Estado do Amazonas e pesquisa de informações em prontuários das gestantes na Maternidades do Município de Manaus, entre 2007 e 2009. RESULTADOS: No período do estudo, foram notificadas 509 gestantes HIV positivas. A taxa de transmissão vertical foi de 9,9 por cento (95 por centoCI: 7.2 - 12.6 por cento). A idade media das pacientes era de 27 anos (SD: 5,7) e a maioria (54,8 por cento) não completou o ensino fundamental. O diagnóstico da infecção pelo HIV foi realizado antes da gravidez em 115 (22,6 por cento) pacientes, durante o pré-natal em 302 (59,3 por cento), no momento do parto em 70 (13,8 por cento) e no puerpério em 22 (4,3 por cento). Quatrocentos e quatro (79,4 por cento) gestantes tiveram acompanhamento pré-natal, com (79,4 por cento) das pacientes recebendo drogas antirretrovirais na gestação e 61,9 por cento dos recém-nascidos recebeu profilaxia antirretroviral. No modelo final de regressão logística multivariada, residir em área urbana [OR=0,7 (95 por centoCI: 0,35-0,89)] e ter realizado pré-natal [OR=0,1 (95 por centoCI: 0,04-0,24)] demonstraram ser fatores protetores da transmissão vertical nesta população. CONCLUSÕES: A relevância de acompanhamento adequado e instituição de medidas já estabelecidas como efetivas em garantir a redução da transmissão vertical do HIV em gestantes e seus recém-nascidos deve ser enfatizada.

The use of polymerase chain reaction to confirm diagnosis in skin biopsies consistent with american tegumentary leishmaniasis at histopathology: a study of 90 cases / Uso da reação em cadeia da polimerase em biópsias de pele para confirmar o diagnóstico histopatológico consistente com leishmaniose tegumentar americana: um estudo de 90 casos

BACKGROUND: Cutaneous leishmaniasis is a chronic, infectious disease caused by protozoa of the genus leishmania. The incidence of this disease is high in Brazil, with 19,746 new cases having been detected in 2008. The presence of amastigotes in the cytoplasm of histiocytes constitutes diagnosis of the disease; however, their presence is rarely found in late lesions, making histological diagnosis difficult. Polymerase chain reaction has been shown to represent a highly sensitive and specific technique for the diagnosis of cutaneous leishmaniasis. OBJECTIVES: To use polymerase chain reaction to evaluate paraffin-embedded skin biopsies with histopathological features consistent with cutaneous leishmaniasis. MATERIAL AND METHODS: Polymerase chain reaction amplification of a 120-base-pair fragment of Leishmania kinetoplast DNA (kDNA) minicircles was performed on 90 skin biopsies. The male/female ratio was 75/15. Mean age was 32.36 years, with a median of 31 years, range 4-72 years. Samples were histologically compatible with cutaneous leishmaniasis but a definitive diagnosis could not be made since amastigotes were not found. All cases were histologically classified according to the patterns described by de Magalhães. RESULTS: According to the de Magalhães classification, the most common histological pattern was type IV (exudative granulomatous reaction), which was found in 65.6 percent of cases (56/90), followed by type I (exudative cellular reaction) in 21.1 percent of cases (19/90) and type III (exudative and necrotic granulomatous reaction) in 12.2 percent of cases (11/90). Leishmania DNA was found in 96.7 percent of the biopsies (87/90). CONCLUSION: Polymerase chain reaction performed by amplifying kDNA is able to confirm a diagnosis of cutaneous leishmaniasis with a high degree of sensitivity in cases in which histopathology is consistent with a diagnosis of cutaneous leishmaniasis but not definitive.

FUNDAMENTOS: Cutaneous leishmaniasis is a chronic, infectious disease caused by protozoa of the genus leishmania. The incidence of this disease is high in Brazil, with 19,746 new cases having been detected in 2008. The presence of amastigotes in the cytoplasm of histiocytes constitutes diagnosis of the disease; however, their presence is rarely found in late lesions, making histological diagnosis difficult. Polymerase chain reaction has been shown to represent a highly sensitive and specific technique for the diagnosis of cutaneous leishmaniasis. OBJECTIVES: To use polymerase chain reaction to evaluate paraffin-embedded skin biopsies with histopathological features consistent with cutaneous leishmaniasis. MATERIAL AND METHODS: Polymerase chain reaction amplification of a 120-base-pair fragment of Leishmania kinetoplast DNA (kDNA) minicircles was performed on 90 skin biopsies. The male/female ratio was 75/15. Mean age was 32.36 years, with a median of 31 years, range 4-72 years. Samples were histologically compatible with cutaneous leishmaniasis but a definitive diagnosis could not be made since amastigotes were not found. All cases were histologically classified according to the patterns described by de Magalhães. RESULTS: According to the de Magalhães classification, the most common histological pattern was type IV (exudative granulomatous reaction), which was found in 65.6 por cento of cases (56/90), followed by type I (exudative cellular reaction) in 21.1 por cento of cases (19/90) and type III (exudative and necrotic granulomatous reaction) in 12.2 por cento of cases (11/90). Leishmania DNA was found in 96.7 por cento of the biopsies (87/90). CONCLUSION: Polymerase chain reaction performed by amplifying kDNA is able to confirm a diagnosis of cutaneous leishmaniasis with a high degree of sensitivity in cases in which histopathology is consistent with a diagnosis of cutaneous leishmaniasis but not definitive.

Coinfecção histoplasmose e Aids / Histoplasmosis and AIDS co-infection

Apresenta-se um caso de coinfecção histoplasmose e Aids, com lesões cutâneas predominantemente papulosas e comprometimento sistêmico. O exame histopatológico e micológico de lesão cutânea confirmou o diagnóstico. Em doentes com Aids, a histoplasmose surge, principalmente, quando a contagem de células T-CD4-positivas é inferior a 50 células/mm³. Nesses casos, a histoplasmose pode ser grave e, se não tratada adequadamente, levar ao êxito letal, como no paciente relatado.

This report concerns an AIDS patient presenting systemic and cutaneous manifestations of histoplasmosis. A histopathological and mycological examination of the skin lesion confirmed the diagnosis. In AIDS patients histoplasmosis arises mainly when the T-CD4+ cell count is less than 50 cells/mm3. In such cases, histoplasmosis can be severe and if left untreated can lead to death, as occurred with this patient.