Clinical and epidemiological study of leprosy cases in the University Hospital of Brasília: 20 years - 1985 to 2005

Hansen's disease, also known as leprosy, is an infectious disease still prevalent in Brazil. It is a chronic illness with acute immunological phenomena known as leprosy reactions. In the Federal District of Brazil, the University Hospital of Brasília is the reference centre for leprosy care. The study aimed to characterize the clinical and epidemiological profile of Hansen's disease patients at the University Hospital of Brasília, by descriptive, retrospective analysis of 1,124 patients over the period from 1985 to 2005. The pattern of leprosy in this study demonstrated that type 2 leprosy reactions were common, especially in the lepromatous form and presented a direct correlation with the bacilloscopic index. The prevalence and frequency of severe complications, such as leprosy reactions, emphasize the importance of the ongoing study of leprosy and the need for continual improvement in the scope of knowledge concerning its treatment.

Clinical variables associated with leprosy reactions and persistence of physical impairment

Introduction Leprosy is a chronic disease that affects skin and peripheral nerves. Disease complications include reactional episodes and physical impairment. One World Health Organization (WHO) goal of leprosy programs is to decrease the number of grade 2 impairment diagnoses by 2015. This study aims to evaluate clinical factors associated with the occurrence of leprosy reactions and physical impairment in leprosy patients. Methods We conducted a retrospective study of data from medical records of patients followed in two important centers for the treatment of leprosy in Aracaju, Sergipe, Brazil, from 2005 to 2011. We used the chi-square test to analyze associations between the following categorical variables: gender, age, operational classification, clinical forms, leprosy reactions, corticosteroid treatment, and physical impairment at the diagnosis and after cure. Clinical variables associated with multibacillary leprosy and/or reactional episodes and the presence of any grade of physical impairment after cure were evaluated using the logistic regression model. Results We found that men were more affected by multibacillary forms, reactional episodes, and grade 2 physical impairment at diagnosis. Leprosy reactions were detected in a total of 40% of patients and all were treated with corticosteroids. However, physical impairment was observed in 29.8% of the patients analyzed at the end of the treatment and our multivariate analysis associated a low dose and short period of corticosteroid treatment with persistence of physical impairments. Conclusions Physical impairment should receive an increased attention before and after treatment, and adequate treatment should be emphasized.

Characteristics of pregnant and lactating women with leprosy

INTRODUCTION: The clinical characteristics of women who conceive during leprosy and the association between leprosy and pregnancy are not well known. METHODS: This cross-sectional study included 49 pregnant or lactating women diagnosed with leprosy in 2011. RESULTS: The patients had a clinical dimorphous form of leprosy (44.9%), no physical incapacity at diagnosis (87.5%), and no complications in either the patient or infant (33.4%). In 36.3% of cases, leprosy symptoms were presented in the last trimester of pregnancy, and in 31.9% of patients were in the first trimester of lactation. CONCLUSIONS: The association between leprosy and pregnancy should be routinely investigated, particularly in endemic areas.

Insights from animal models on the immunogenetics of leprosy: a review

A variety of host immunogenetic factors appear to influence both an individual's susceptibility to infection with Mycobacterium leprae and the pathologic course of the disease. Animal models can contribute to a better understanding of the role of immunogenetics in leprosy through comparative studies helping to confirm the significance of various identified traits and in deciphering the underlying mechanisms that may be involved in expression of different disease related phenotypes. Genetically engineered mice, with specific immune or biochemical pathway defects, are particularly useful for investigating granuloma formation and resistance to infection and are shedding new light on borderline areas of the leprosy spectrum which are clinically unstable and have a tendency toward immunological complications. Though armadillos are less developed in this regard, these animals are the only other natural hosts of M. leprae and they present a unique opportunity for comparative study of genetic markers and mechanisms associable with disease susceptibility or resistance, especially the neurological aspects of leprosy. In this paper, we review the recent contributions of genetically engineered mice and armadillos toward our understanding of the immunogenetics of leprosy.

Obesity and gestational weight gain: cesarean delivery and labor complications

OBJECTIVE: To assess the association between pre-gestational obesity and weight gain with cesarean delivery and labor complications. METHODS: A total of 4,486 women 20-28 weeks pregnant attending general prenatal care clinics of the national health system in Brazil from 1991 to 1995 were enrolled and followed up through birth. Body mass index categories based on prepregnancy weight and total weight gain were calculated. Associations between body mass index categories and labor complications were adjusted through logistic regression analysis. RESULTS: Obesity was present in 308 (6.9%) patients. Cesarean delivery was performed in 164 (53.2%) obese, 407 (43.1%) pre-obese, 1,045 (35.1%) normal weight and 64 (24.5%) underweight women. The relative risk for cesarean delivery in obese women was 1.8 (95% CI: 1.5-2.0) compared to normal weight women. Greater weight gain was particularly associated with cesarean among the obese (RR 4th vs 2nd weight gain quartile 2.2; 95% CI: 1.4-3.2). Increased weight at the beginning of pregnancy was associated with a significantly higher adjusted risk of meconium with vaginal delivery and perinatal death and infection in women submitted to cesarean section. Similarly, greater weight gain during pregnancy increased the risk for meconium and hemorrhage in women submitted to vaginal delivery and for prematurity with cesarean. CONCLUSIONS: Pre-gestational obesity and greater weight gain independently increase the risk of cesarean delivery, as well as of several adverse outcomes with vaginal delivery. These findings provide further evidence of the negative effects of prepregnancy obesity and greater gestational weight gain on pregnancy outcomes.

Retreatment in leprosy: a case-control study

OBJECTIVE: To assess risk factors for retreatment of leprosy patients. METHODS: A case-control study with patients from two reference care units in Recife, northeastern Brazil, in 2003. The case group included retreated patients (N=155) and the control group comprised those patients who were not retreated (N=155) matched by year of diagnosis and health care unit. Univariate and multivariate analyses were conducted to test the associations and odds ratios and related 95% confidence intervals were estimated. RESULTS: The following factors were found to be significantly associated (p<0.05) with retreatment: occurrence of adverse immunological reactions after treatment completion (OR=2.3; 95% CI=1.18;4.83), final bacterial index > 1 (OR=6.43; 95% CI=1.67;24.74), therapeutic regimen consisting of sulfone monotherapy (OR=10; 95% CI=0.01;0.78) and reports of household contacts (OR=2.2; 95% CI=0.24;0.85). CONCLUSIONS: The study findings reinforce that the use of dapsone monotherapy should be discontinued, and highlight the need for epidemiological monitoring of specific groups of leprosy patients after treatment completion through periodical clinical and laboratory evaluation. Further studies to explore the association between final bacterial index and retreatment are strongly recommended.

Spatial analysis of leprosy incidence and associated socioeconomic factors

OBJECTIVE: To identify clusters of the major occurrences of leprosy and their associated socioeconomic and demographic factors. METHODS: Cases of leprosy that occurred between 1998 and 2007 in São José do Rio Preto (southeastern Brazil) were geocodified and the incidence rates were calculated by census tract. A socioeconomic classification score was obtained using principal component analysis of socioeconomic variables. Thematic maps to visualize the spatial distribution of the incidence of leprosy with respect to socioeconomic levels and demographic density were constructed using geostatistics. RESULTS: While the incidence rate for the entire city was 10.4 cases per 100,000 inhabitants annually between 1998 and 2007, the incidence rates of individual census tracts were heterogeneous, with values that ranged from 0 to 26.9 cases per 100,000 inhabitants per year. Areas with a high leprosy incidence were associated with lower socioeconomic levels. There were identified clusters of leprosy cases, however there was no association between disease incidence and demographic density. There was a disparity between the places where the majority of ill people lived and the location of healthcare services. CONCLUSIONS: The spatial analysis techniques utilized identified the poorer neighborhoods of the city as the areas with the highest risk for the disease. These data show that health departments must prioritize politico-administrative policies to minimize the effects of social inequality and improve the standards of living, hygiene, and education of the population in order to reduce the incidence of leprosy.

Spatial patterns of leprosy in a hyperendemic state in Northern Brazil, 2001-2012

ABSTRACT OBJECTIVE To describe the spatial patterns of leprosy in the Brazilian state of Tocantins. METHODS This study was based on morbidity data obtained from the Sistema de Informações de Agravos de Notificação (SINAN – Brazilian Notifiable Diseases Information System), of the Ministry of Health. All new leprosy cases in individuals residing in the state of Tocantins, between 2001 and 2012, were included. In addition to the description of general disease indicators, a descriptive spatial analysis, empirical Bayesian analysis and spatial dependence analysis were performed by means of global and local Moran’s indexes. RESULTS A total of 14,542 new cases were recorded during the period under study. Based on the annual case detection rate, 77.0% of the municipalities were classified as hyperendemic (> 40 cases/100,000 inhabitants). Regarding the annual case detection rate in < 15 years-olds, 65.4% of the municipalities were hyperendemic (10.0 to 19.9 cases/100,000 inhabitants); 26.6% had a detection rate of grade 2 disability cases between 5.0 and 9.9 cases/100,000 inhabitants. There was a geographical overlap of clusters of municipalities with high detection rates in hyperendemic areas. Clusters with high disease risk (global Moran’s index: 0.51; p < 0.001), ongoing transmission (0.47; p < 0.001) and late diagnosis (0.44; p < 0.001) were identified mainly in the central-north and southwestern regions of Tocantins. CONCLUSIONS We identified high-risk clusters for transmission and late diagnosis of leprosy in the Brazilian state of Tocantins. Surveillance and control measures should be prioritized in these high-risk municipalities.

Associantion between leprosy and hepatitis B infecion: a survey in Goiânia, Central Brazil

This investigation presents the results of Hepatitis B virus screening among leprosy patients conducted in Central Brazil as a preliminary information for a HBV vaccination programme. The main objectives were to assess the seroprevalence of HBV serum markers among lepromatous patients and to analyse institutionalization as risk factor for HBV infection in this population. Two groups of lepromatous patients were studied, 83 outpatients and 171 institutionalized ones. Screening for HBV serum markers included the detection of HBsAg, anti-HBc by radioimmune assay (RIA). The prevalence of carrier state (HBsAg) was 4.8% and 8.8% among outpatients and institutionalized, respectively, (p>0.05). Seroprevalence of exposure (all markers) was statistically significant different between outpatients (16.9%) and institutionalized ones (50.3%). Institutionalized patients had an almost four fold risk of HBV infection when compared to the outpatients, and the highest risks were among patients with more than 21 years of residence in the colony, after adjusting for age and sex.

Respiratory complications in Brazilian patients infected with human immunodeficiency virus

PURPOSE: To determine how often and by what means an indentifiable pulmonary pathogen can be recognized in human immunodeficiency virus (HIV) infected patients with respiratory disorders in Brazil, which are the most frequently observed microorganisms and what impact specific therapy has on these agents. PATIENTS AND METHODS: Thirty-five HIV seroposiüve subjects with respiratory complaints were studied. All patients had a complete history, physical examination and blood counts. The pulmonary assessment included chest radiograms; sputum examination for bacterial and fungal pathogens; bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. Patients with treatable complications received standard antimicrobial therapy. RESULTS: One or more microorganisms were found in 24 subjects and another 3 individuals showed nonspecific interstitial pneumonitis. The sputum examination identified the pulmonary pathogens in 7 cases. The bronchoalveolar lavage and the histopathologic examination were diagnostic in 14% and 83%, respectively, of the 28 individuals that were submitted to bronchoscopy. The most frequently identified microorganism was P. carinii (55%), followed by M. tuberculosis (41%) and cytomegalovirus (8%). The clinical, laboratory and radiographic findings failed to distinguish the specific pulmonary pathogens. Twenty-three individuals with P. carinii pneumonitis and/or tuberculosis received specific therapy; among the evaluable patients the therapeutic response rates were 79% for PCP and 100% for TB. CONCLUSIONS: We have determined that tuberculosis, P. carinii and cytomegalovirus pneumonitis are the most common respiratory opportunistic diseases in Brazilian patients infected with HIV. The histologic evaluation was crucial in order to identify the pulmonary pathogens. Tuberculosis in AIDS individuals displayed clinical and radiographic findings atypical for reactivation disease. However, most of the features observed in HIV infected patients had been previously described in infection of the normal host. Furthermore, the AIDS subjects showed a good therapeutic response to anti-tuberculous drugs.

Bacterial agents isolated from cerebrospinal fluid of patients with Acquired Immunodeficiency Syndrome (AIDS) and neurological complications

Cerebrospinal fluid (CSF) samples from 2083 patients with acquired immunodeficiency syndrome (AIDS) and neurological complications were bacteriologically examined during a period of 7 years (1984-1990). The percentage of patients who had at least one bacterial agent cultured from the CSF was 6.2%. Mycobacterium tuberculosis was the most frequently isolated agent (4.3%), followed by Mycobacterium avium complex or MAC (0.7%), Pseudomonas spp (0.5%), Enterobacter spp (0.4%), and Staphylococcus aureus (0.3%). Among 130 culture positive patients, 89 (68.5%) had M. tuberculosis and 15 (11.6%) had MAC. The frequency of bacterial isolations increased from 1988 (5.2%) to 1990 (7.2%), partly due to the increase in MAC isolations. Bacterial agents were more frequently isolated from patients in the age group 21-30 years and from women (p<0.05).

Pattern of mycobacterial antigen detection in leprosy

Immunohistochemistry reaction (Peroxidase anti-peroxidase - PAP) was carried out on fifty-two skin biopsies from leprosy patients with the purpose to identify the antigenic pattern in mycobacteria and to study the sensitivity of this method. Five different patterns were found: bacillar, granular, vesicular, cytoplasmatic and deposits, classified according to the antigenic material characteristics. Deposits (thinely particulate material) appeared more frequently, confirming the immunohistochemistry sensitivity to detect small amounts of antigens even when this material is not detected by histochemical stainings.

ANTI M. leprae IgM ANTIBODY DETERMINATION BY ULTRAMICROIMMUNOENZYMATIC (UMELISA HANSEN) FOR THE DIAGNOSIS AND MONITORING LEPROSY

The relationship between the IgM antibody response, antigenic load as well as the clinical improvement after chemotherapy was studied in order to obtain useful data for the early diagnosis and monitoring leprosy. A level of 82% (94/115) agreement was obtained between IgM UMELISA HANSEN and slitskin smear examination. Discrepant results were observed in 16 patients who showed positive IgM response despite negative by the skin smear examination. In these patients, the IgM response was seen to be associated to the early signal for bacilli recurrence in the skin. In one of these patients the presence of bacilli was demonstrated in the skin, two months after IgM antibodies being detected by UMELISA HANSEN. Also in one of the treated patients positive by both diagnostic techniques, a remarkable decrease in the IgM antibody levels was seen, correlating with a significant clinical improvement. Moreover it was found a direct relationship between the IgM antibody response and bacterial antigenic load, regardless the time elapsed in the disease's evolution.

Anti-phenolic glycolipid-I (PGL-I) determination using blood collection on filter paper in leprosy patients

The authors studied 70 leprosy patients and 20 normal individuals, comparing the traditional sera collection method and the finger prick blood with the conservation on filter paper for specific antibodies against the native phenolic glycolipid-I (PGL-I) from Mycobacterium leprae. The finger prick blood dried on filter paper was eluated in phosphate buffer saline (PBS) containing 0.5% gelatin. The classical method for native PGL-I was performed for these eluates, and compared with the antibody determination for sera. It was observed that there is a straight correlation comparing these two methods; although the titles found for the eluates were lower than those obtained for serology. This blood collection method could be useful for investigation of new leprosy cases in field, specially in contacts individuals.