Late relapses in leprosy patients in Brazil: 10-year post-trial of uniform multidrug therapy (U-MDT/CT-BR)

ABSTRACT Background: Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas. Objectives: To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT. Methods: The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables. Results: The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio. Conclusions: The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide. Trial registration: ClinicalTrials.gov: NCT00669643.

Main etiological agents identified in 170 men with urethritis attended at the Fundação Alfredo da Matta, Manaus, Amazonas, Brazil,

Abstract Background: Sexually transmitted infections (STI) are a global public health problem. Urethritis are among the most common STIs, and can cause several complications and facilitate the transmission of the HIV virus. Objectives: To investigate the main etiologic agents of urethritis in 170 men treated at Fundação Alfredo da Matta. Methods: To identify the agents, urethral exudate and urine were collected. Gram and culture tests were performed in Thayer-Martin medium for Neisseria gonorrhoeae and polymerase chain reaction for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, Mycoplasma genitalium, and herpes simplex types 1 and 2. Results: N. gonorrhoeae were identified in 102 (60.0%) patients, C. trachomatis in 50 (29.4%), U. urealyticum in 29 (17.0%), M. genitalium in 11 (6.5 %), U. parvum in ten (5.9%), and M. hominis in seven (4.1%). Herpes simplex type 2 was diagnosed in 24 (21.6%) of the 111 patients who underwent PCR for this pathogen. In 69 cases there was co-infection; the most frequent were: N. gonorrhoeae and C. trachomatis in 21 (14.7%) patients; N. gonorrhoeae and C. trachomatis in 21 (12.4%) patients; N. gonorrhoeae and herpes simplex type 2 in 11 (6.5%), and N. gonorrhoeae and U. urealyticum in nine (5.3%). Study limitations: Not relevant. Conclusion: N. gonorrhoeae, C. trachomatis, U. urealyticum, and herpes simplex type 2 were the pathogens most frequently identified in the present study. The main coinfection found was N. gonorrhoeae and C. trachomatis. T. vaginalis and herpes simplex type 1 were not identified in any of the patients.

Atypical manifestations of recent syphilis: study of 19 cases

Abstract Background: Syphilis is one of the most common diseases that start with genital ulcers. Aside from the initial, classic ulcerative lesion of syphilis, called hard chancre, atypical presentations are common, with erosions, erythema, edema, balanitis, and other dermatological manifestations. Associated with initial genital lesions, the presence of inguinal adenopathies is frequent, and the presence of hardened and painless lymphangitis on the dorsum of the penis is rare. Objectives: To describe atypical penile manifestations in patients with early syphilis. Methods: The present study reports patients who developed cord-like lesions on the penis. Results: The study included 25 patients with cord-like lesions on the penis; in 19 of those, the diagnosis of syphilis was confirmed. Study limitations: Small number of patients included. Conclusions: In view of the findings of the present investigation, it is important to emphasize that all patients who present with cord-like lesions on the penis must undergo a rapid test for syphilis, VDRL, serologies for HIV viral hepatitis B and C and, whenever possible, histopathological and Doppler exams.

Clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): adverse effects approach

Abstract: BACKGROUND: The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs. OBJECTIVE: Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). Patients and methods: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial. RESULTS: Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported. STUDY LIMITATIONS: Loss of some monthly laboratory sample collection. CONCLUSIONS: There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Case for diagnosis. Atypical genital lesion

Abstract: We present a case of a penile lesion with a clinical appearance similar to Mondor penile disease (thrombosis of the dorsal vein of the penis) or penile sclerosing lymphangitis. Laboratory evaluation, however, showed a solid lesion, with no vascular component to Doppler ultrasonography and no treponema to immunohistochemistry. Histological and serological tests were compatible with secondary syphilis. The authors reinforce the need for the inclusion of syphilis in the differential diagnosis of penile cord injuries.

Leprosy: current situation, clinical and laboratory aspects, treatment history and perspective of the uniform multidrug therapy for all patients

Abstract: In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.

Efficacy and safety of a single dose pentamidine (7mg/kg) for patients with cutaneous leishmaniasis caused by L. guyanensis: a pilot study

Abstract: BACKGROUND: There have been few studies on pentamidine in the Americas; and there is no consensus regarding the dose that should be applied. OBJECTIVES: To evaluate the use of pentamidine in a single dose to treat cutaneous leishmaniasis. METHODS: Clinical trial of phase II pilot study with 20 patients. Pentamidine was used at a dose of 7 mg/kg, in a single dose. Safety and adverse effects were also assessed. Patients were reviewed one, two, and six months after the end of treatments. RESULTS: there was no difference between the treatment groups in relation to gender, age, number or location of the lesions. Pentamidine, applied in a single dose, obtained an effectiveness of 55%. Mild adverse events were reported by 17 (85%) patients, mainly transient pain at the site of applications (85%), while nausea (5%), malaise (5%) and dizziness (5%) were reported in one patient. No patient had sterile abscess after taking medication at a single dose of 7mg/kg. CONCLUSIONS: Clinical studies with larger samples of patients would enable a better clinical response of pent amidine at a single dose of 7mg, allowing the application of more powerful statistical tests, thus providing more evidences of the decrease in the effectiveness of that medication. Hence, it is important to have larger studies with new diagrams and/or new medications.

High-risk human papillomavirus and cervical lesions among women living with HIV/AIDS in Brazilian Amazon, Brazil

ABSTRACT OBJECTIVE: The goal of this study was to determine the prevalence of human papillomavirus infection infection and cervical lesions and its associated factors among HIV infected women attending an AIDS clinic in Amazonas state, Brazil. METHODS: Cross-sectional study. Women attending an AIDS clinic in the city of Manaus between March and December 2011 for gynecological examination were invited to participate. Enrolled patients answered a standardized interview including demographical, behavioral, and clinical data. Additionally, patients underwent a gynecological evaluation with collection of cervical samples for cytological analysis and high-risk human papillomavirus infection hybrid capture. A blood sample was also obtained to determine CD4 and viral load levels. RESULTS: A total of 310 (82.9%) women participated in the study. High-risk human papillomavirus infection was detected in 191 (61.6%) cases; 24 (13.5%) had low-grade squamous intraepithelial lesion (SIL) and 4 (2.2%) high-grade SIL. No invasive cervical cancer was diagnosed. Median age was 32 (interquartile range (IQR): 27-38) years and median of education was 8.5 (IQR 4-11) years of schooling and 56.1% had a monthly income up to US$180. In multivariate analysis, being less than 30 years old [OR = 1.7 (95% CI: 1.2-2.4,p = 0.005)], high-grade SIL [OR = 6.5 (95% CI: 1.6-23.0, p = 0.009)], and CD4 counts <200 cells/mm3 [OR = 1.6 (95% CI: 1.2-2.0, p < 0.001)] were associated with high risk human papillomavirus infection infection. CONCLUSIONS: In the present study high-risk human papillomavirus infection was frequent and it was associated to high-SIL. These results show the importance of gynecologic examinations in routine care and follow-up required by those who present with cervical lesions.

A historical overview of leprosy epidemiology and control activities in Amazonas, Brazil

Leprosy is an ancient infectious disease caused by Mycobacterium leprae. According to comparative genomics studies, this disease originated in Eastern Africa or the Near East and spread with successive human migrations. The Europeans and North Africans introduced leprosy into West Africa and the Americas within the past 500 years. In Brazil, this disease arrived with the colonizers who disembarked at the first colonies, Rio de Janeiro, Salvador and Recife, at the end of the sixteenth century, after which it was spread to the other states. In 1854, the first leprosy cases were identified in State of Amazonas in the north of Brazil. The increasing number of leprosy cases and the need for treatment and disease control led to the creation of places to isolate patients, known as leprosaria. One of them, Colonia Antônio Aleixo was built in Amazonas in 1956 according to the most advanced recommendations for isolation at that time and was deactivated in 1979. The history of the Alfredo da Matta Center (AMC), which was the first leprosy dispensary created in 1955, parallels the history of leprosy in the state. Over the years, the AMC has become one of the best training centers for leprosy, general dermatology and sexually transmitted diseases in Brazil. In addition to being responsible for leprosy control programs in the state, the AMC has carried out training programs on leprosy diagnosis and treatment for health professionals in Manaus and other municipalities of the state, aiming to increase the coverage of leprosy control activities. This paper provides a historical overview of leprosy in State of Amazonas, which is an endemic state in Brazil.

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.

Trichomonas vaginalis and associated factors among women living with HIV/AIDS in Amazonas, Brazil

OBJECTIVES: Our goal was to determine the prevalence of Trichomonas vaginalis and its associated factors among women living with HIV attending an AIDS clinic in Manaus, Amazonas, Brazil. METHODS: Cross-sectional study among women attending an AIDS clinic in Manaus between March and December 2010 for gynecological examination were invited to participate. Enrolled patients answered a face-to-face interview including demographic, behavioral and clinical data. They also underwent a gynecological evaluation and cervical scrape samples were collected for wet mount, Gram stain, culture and cytological analysis. A blood sample was obtained to determine TCD4+ lymphocytes and viral load. RESULTS: A total of 341 (91.2%) women participated in the study. The prevalence of T. vaginalis was 4.1% (95% CI: 2.0-6.2%). Median age was 32 (interquartile range 27-38) years and median years of schooling was 9.0 (interquartile range 4-11). A total of 165 (53.2%) HIV women were classified as patients with AIDS. In multivariate analyses, squamous intraepithelial lesions in cytology [OR = 2.46 (95% CI: 1.31-4.63, p = 0.005)] and anal sex practice [OR = 3.62 (95% CI: 1.08-12.19, p = 0.037)] were associated with T. vaginalis. CONCLUSIONS: These results highlight that HIV-infected women should be screened for T. vaginalis. The control of this infection may have an impact on preventing reproductive complications among these women.

Lymphangiectatic Kaposi's sarcoma in a patient with AIDS / Sarcoma de Kaposi linfangiectásico em paciente com Aids

Kaposi's sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi's sarcoma. In non-HIV-associated Kaposi's sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi's sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis's sarcoma. .

O sarcoma de Kaposi é uma neoplasia originária do endotélio linfatico, que apresenta um amplo espectro de manifestações, com quatro formas clínicas: sarcoma de Kaposi clássico, endêmico, iatrogêncio e epidêmico ou associado ao HIV. Em pacientes imunocompetentes, a doença é tipicamente limitada às extremidades. Porém em pacientes imunideprimidos, o sarcoma de Kaposi é uma doença sistêmica multifocal. Apresenta cursos clínicos diferentes, desde simples lesões cutâneas isoladas até lesões agressivas e difusas, com ou sem envolvimento sistêmico. Lesões avançadas de sarcoma de Kaposi, principalmente as localizadas nas extremidades, podem apresentar linfedema. Neste trabalho, reportamos caso de paciente com forma rara de Sarcoma de Kaposi associado a Aids, chamada de sarcoma de Kaposi linfangiectásico. .