Multibacillary Forms Research Articles

Investigation of a Medieval Pilgrim Burial Excavated from the Leprosarium of St Mary Magdalen Winchester, UK

We have examined the remains of a Pilgrim burial from St Mary Magdalen, Winchester. The individual was a young adult male, aged around 18–25 years at the time of death. Radiocarbon dating showed the remains dated to the late 11th–early 12th centuries, a time when pilgrimages were at their height in Europe. Several lines of evidence in connection with the burial suggested this was an individual of some means and prestige. Although buried within the leprosarium cemetery, the skeleton showed only minimal skeletal evidence for leprosy, which was confined to the bones of the feet and legs. Nonetheless, molecular testing of several skeletal elements, including uninvolved bones all showed robust evidence of DNA from Mycobacterium leprae, consistent with the lepromatous or multibacillary form of the disease. We infer that in life, this individual almost certainly suffered with multiple soft tissue lesions. Genotyping of the M.leprae strain showed this belonged to the 2F lineage, today associated with cases from South-Central and Western Asia. During osteological examination it was noted that the cranium and facial features displayed atypical morphology for northern European populations. Subsequently, geochemical isotopic analyses carried out on tooth enamel indicated that this individual was indeed not local to the Winchester region, although it was not possible to be more specific about their geographic origin.

Sociodemographic and epidemiological profile of leprosy patients in an endemic region in Brazil.

The incidence of Hansen's disease is high in overlooked populations. Data of Hansen's disease cases reported in the information system of the Department of Informatics, Brazilian Unified Health System, from 2013 to 2014 were analyzed. Among 434 studied cases of Hansen's disease, the female sex (52.5%), adult age (73.7%), low educational level (61.8%), and multibacillary form were associated with higher prevalence rates. Hansen's disease is more frequent among female adults with a low educational level, and the prevalence of multibacillary leprosy reflects disease detection at late stages.

P022 HLA-DRB1 and HLA-DQA1/B1 alleles in association with leprosy compared to household contacts

Aim The aim of this study was to investigate the association between HLA-DRB1 and DQA1 / DQB1 genetic polymorphisms in leprosy patients and their domiciliary contacts from Southern Brazil. Methods This study was conducted with 183 leprosy patients and 238 healthy controls that had prolonged contact with the patient but are not blood relatives. The polymorphisms DRB1 and DQA1 / DQB1 genes were analyzed by PCR-SSOR, using the Luminex® technology. The DQA1 / DQB1 and HLA-DRB1 (High Resolution) genotypes were used LABType® SSO Kit. Statistical analysis was performed using the Chi-square with the Yates’s or Fisher’s exact test, and Bonferroni correction ( Pc ) was also applied. This study was approved by the Ethics Committees. Results The sample evaluated was in HW Equilibrium. The allelic group frequencies showed that DQA1 ∗ 03, DQB1 ∗ 03 and DRB1 ∗ 04 were significantly higher in the control group than in patients leprosy per se ( DQA1 ∗ 03 = 17.2% vs. 11.8%, OR = 0.6, 95% CI 0.4–0.95, P = 0.026, Pc = 0.16), ( DQB1 ∗ 03 = 33.2% vs. 26.5%, OR = 0.7, 95% CI 0.5–0.98, P = 0.043, Pc = 0.25) and ( DRB1 ∗ 04 = 14.9% vs. 8.2%, OR = 0.5, 95% CI 0.3–0.8, P = 0,003, Pc = 0.046), respectively. A protective association was also observed between the multibacillary (MB) clinical form and the DRB1 ∗ 04 and DQA1 ∗ 03 alleles, while DQA1 ∗ 1 was associated with susceptibility (47.3% vs. 39.5%, OR = 1.4, 95% IC 1.0–1.8, P = 0.038, Pc = 0.232). The DRB1 ∗ 14- DQA1 ∗ 01- DQB1 ∗ 06 haplotype was associated with susceptibility to leprosy per se (1.1% vs. 0%, OR = 11.8, 95% IC 1.95 – undefined, P = 0.03, Pc = 0.39) and to the MB clinical form (1% vs. 0%, OR = 11.3, 95% IC = 1.4 – undefined, P = 0.043, Pc = 0.56). In addition, DRB1 ∗ 15:02 and DQB1 ∗ 06:01 alleles were associated with susceptibility to leprosy per se and to the MB form. On the other hand, DQA1 ∗ 03:01 (1.4% vs. 5.0%, OR = 0.3, 95% IC = 0.9–0.7, P = 0.004, Pc = 0.03) and DQB1 ∗ 03:02 (4.4% vs. 10.5%, OR = 0.4, 95% IC = 0.2–0.7, P = 0.001, Pc = 0.009) suggests a protective association to leprosy per se and the MB form compared to controls. Conclusion This study confirmed that polymorphisms in DQA1/DQB1 and DRB1 genes may influence the development/protection of leprosy and also have some influence in clinical forms of the disease.

Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages.

Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis.

Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases.

After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes.Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy.

Serum uric acid levels during leprosy reaction episodes.

Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions.Methods. The study included patients aged 18–69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively).Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment.Discussion. The decreased serum UA levels in patients with type 2 leprosy reactions might be due to the consumption of UA to neutralize the enhanced production of oxygen- and nitrogen-reactive species that occurs during type 2 reactions. The maintenance of the reduced levels in the follow-up assessments may indicate persistence of oxidative stress in the initial post-treatment stages, despite improved clinical conditions. The results of this study suggest that serum UA may play an antioxidative role during type 2 leprosy reactions.

Leprosy in a University Hospital in Southern Brazil.

BACKGROUNDLeprosy is an infectious disease that may lead to irreversible nerve damage, compromising patient's quality of life and leading to loss of working years.OBJECTIVESTo evaluate the epidemiological profile of patients followed at a University Hospital.MATERIALS AND METHODSThis is a retrospective observational study, based on a review of medical records. We studied the clinical and epidemiological features of patients with leprosy monitored at the Hospital de Clínicas of the Federal University of Paraná between January 2005 and January 2010.RESULTSThe mean age was 47.51, while 35.94% of patients were aged 41-60. The male:female rate was 1.8:1. The most prevalent occupations were: retired, students or rural workers. Patients came mainly from Curitiba or nearby areas, but there were also patients from the countryside. The mean diagnostic delay was 24.57 months. Multibacillary forms prevailed, with the lepromatous variety being the most common, closely followed by the borderline type. Neural enlargement was found in more than 50% of the patients and 48.44% of them developed reactional states. Hemolysis was the most commonly detected drug side effect. Initial functional evaluation was possible in 70% of patients, 55% of whom had disabilities upon diagnosis. The most prevalent associated disease was hypertension.CONCLUSIONSThis study showed an important diagnostic delay and a high rate of sequelae in this specific population. Brazil is one of the few remaining countries that has not yet eradicated leprosy and it is important to improve health policies in order to prevent sequelae and achieve eradication.

Clinical variables associated with disability in leprosy cases in northeast Brazil.

The clinical outcomes of leprosy include complications such as physical disabilities and deformities that vary according to the degree of impairment of nerve trunks. Knowledge of the factors that lead to the development of these complications is important for disability prevention programs. This study aimed to evaluate clinical factors associated with the occurrence of physical disability in leprosy cases. This was a retrospective study of 2,358 cases of leprosy in Aracaju, northeast Brazil, between 2001 and 2011. Analysis was done using the Chi-square test and logistic regression model. Significant factors associated with disability were found to be male gender, having more than two affected nerves, multibacillary leprosy classification, leprosy reaction, and lepromatous leprosy. The multivariate analysis revealed that the associated factors included having more than two affected nerves, leprosy reaction (adjusted odds ratio [aOR]: 2.02, 95% confidence interval [CI]: 1.36 to 3.01), the multibacillary form (aOR: 2.74, 95% CI: 1.84 to 4.08), and lepromatous leprosy (aOR: 4.87, 95% CI: 2.86 to 16.08). The number of affected nerves, leprosy reaction, operational classification, and clinical presentation were identified as the main factors associated with the development of disability in leprosy patients.

Leprosy nephropathy: a review of clinical and histopathological features.

Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes.

TH17 cells, interleukin-17 and interferon-γ in patients and households contacts of leprosy with multibacillary and paucibacillary forms before and after the start of chemotherapy treatment.

Studies on the immunology of leprosy are fundamental to the understanding of the various forms of clinical manifestation of the disease. In some diseases, lymphocytes TH17 and one of its key cytokines, interleukin-17 has been shown to be essential in developing an effective immune response. In leprosy, involvement of lymphocyte TH17 and interleukin-17 remains understudied. This study is the first investigation to examine the association between TH17 cells, interleukin-17 and interferon- γ in patients and households contacts of leprosy. To document the participation of TH17 cells and interleukin-17 in the immunology of leprosy, to observe the behavior of interferon-γ in relation to interleukin-17 and to verify the differences found between individuals paucibacillary, multibacillary and household contacts, we analyzed samples peripheral blood to identify TH-17 cells, interleukin-17 and IFN-γ; establishing relationships between all the groups. There was a significant difference in the results found in the comparison between the paucibacillary and multibacillary groups of patients (P < 0.001), as well with the household contacts (P < 0.005). The polychemotherapeutic treatment modified the profile of immune response in multibacillary patients compared to what was observed before the start of treatment. The principal finding was that TH17 lymphocytes and interleukin-17 actively participating in the immune response of Hansen's disease as well these cells can stimulate the cellular immunity.

Physical disability and social participation in patients affected by leprosy after discontinuation of multidrug therapy

To describe the social participation frequency and the physical disability of patients who were discharged after the multidrug therapy (MDT/WHO) and factors associated with these variables. A cross-sectional and analytical study, examining associations, which took place Nova Iguaçu/Brazil. A random sample of patients treated with multidrug therapy from 1997 to 2006 was selected. The rationale for sample size was determined by the estimated proportion of physical disability in the amount of 23%, with an acceptable sampling error rate of 5%; significance level was established as 5% among the 1080 patients finally a total sample of 225 patients. The evaluations were performed from January 2010 to December 2011 and Socio-demographic and clinical data were collected from the applications completed in the national notifiable diseases information system (SINAN). In the period of interest, 2179 cases were diagnosed with leprosy; 1080 met the criteria for inclusion. Of these, 225 were randomly selected patients who had mean age 56.12 (±17.34 years), 55.6% were women, 39.9% went to high school and 28.9% were Caucasians. A total of 55.3% (125) showed multibacillary form, with a predominant dimorphous leprosy in 40.4%. Physical disability was present in 60.9% and social restrictions in 24.9% of patients. The variable physical disability was associated with the therapeutic regimen multibacillary and social participation. We observed a high frequency of disability and social restriction after long period after the start of MDT/WHO suggesting the late diagnosis of leprosy or inadequate follow-up after discharge. This study highlights the importance of systematic monitoring of these patients with their own criteria which could be held at the Family Health Strategy.

Epidemiological situation of leprosy in Salvador from 2001 to 2009

Mycobacterium leprae was first described as the bacillus that causes leprosy, a chronic granulomatous infectious disease, in 1873 by Amauer Hansen. Leprosy is part of a group of 10 neglected diseases and Bahia has endemic levels of this illness, varying between high and very high. The detection of 52 new cases of leprosy in children under 15 years old in Salvador in 2006 is alarming, and suggests an early contact with the disease. The aim of this review is to analyze the epidemiological situation, the detection rate and evaluate the clinical and epidemiological profile of leprosy in Salvador, in the period 2001-2009. A retrospective cross-sectional study was performed using secondary data collected at Notifiable Diseases Information System Database (SINAN) through the notification of patients with leprosy. Over these nine years 3,226 patients were reported, with a predominance of: females (51.5%), and clinical multibacillary forms in the general population (51.7%), but when we analyze those under 15 years old, paucibacillary forms (tuberculoid + indeterminate) prevailed. The tuberculoid form was the most diagnosed type of presentation. The annual detection rate in Salvador remained at a very high level of endemicity during the studied period and for those under 15 years old it ranged between high and very high. Grade 2 disabilities both at the time of diagnosis and at discharge after cure, varied between low and medium. Based on these data we conclude that the high levels of leprosy detection rates in the general population, plus the variation between high and very high levels in those under 15 years old, associated with the medium level of grade 2 disabilities at the time of diagnosis and discharge, demonstrate the need for improvement on the existing services, investment in active case finding and training of the healthcare professionals in Salvador.

Increased Frequency of CD4 and CD8 Regulatory T Cells in Individuals under 15 Years with Multibacillary Leprosy

BackgroundLeprosy is a chronic disease, caused by Mycobacterium leprae, which poses a serious public health problem worldwide. Its high incidence in people under 15 years old in Ceará state, Brazil, reflects the difficulty of its control. The spectrum of clinical manifestations is associated with the immune response developed, with the Th1 and Th2 responses being related to the paucibacillary and multibacillary forms, respectively. Regulatory T cells (Treg), which can suppress Th1 and Th2 response, have received special attention in the literature and have been associated with development of chronic infections. However, their role in leprosy in individuals under 15 years old has not yet been elucidated. We evaluated the frequency of CD4+/CD8+CD25highFOXP3+ and CD4+/CD8+CD25highFOXP3high cells in leprosy patients and household contacts, in both cases under 15 years old.Methodology/Principal FindingsPBMC from 12 patients and 17 contacts were cultured for 72 hours with anti-CD3 and anti-CD28 (activators) or with activators associated with total sonicated fraction of M. leprae. After culture, the frequency of CD4+/CD8+ Treg was identified by flow cytometry. Cells stimulated by activators and antigen from multibacillary patients showed Treg frequencies almost two times that of the contacts: CD4+FOXP3+ (21.93±8.43 vs. 13.79±8.19%, p = 0.0500), CD4+FOXP3high (10.33±5.69 vs. 5.57±4.03%, p = 0.0362), CD8+FOXP3+ (13.88±9.19 vs. 6.18±5.56%, p = 0.0230) and CD8+FOXP3high (5.36±4.17 vs. 2.23±2.68%, p = 0.0461). Furthermore, the mean fluorescence intensity of FOXP3 in Treg was higher in multibacillary patients than in the contacts. Interestingly, there was a positive correlation of the bacillary index and number of lesions with the frequency of all Treg evaluated in patients.Conclusions/SignificanceWe have demonstrated for the first time that multibacillary leprosy patients under 15 years old have greater CD4+ and CD8+ Treg frequencies and these correlate with clinical and laboratorial aspects of disease. These findings suggest the involvement of these cells in the perpetuation of M. leprae infection.

Clinical variables associated with leprosy reactions and persistence of physical impairment

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. 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. 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. Physical impairment should receive an increased attention before and after treatment, and adequate treatment should be emphasized.

Wade histoid Leprosy: histological and immunohistochemical analysis

Histoid leprosy is a rare multibacillary form that presents with disseminated papule-nodular cutaneous lesions. To study the inflammatory infiltrate of the histoid form and to compare it with other lepromatous forms, we performed histological and immunohistochemical analysis on skin biopsies. Fifteen patients were included for histopathological analysis (10 histoid and five lepromatous) via the haematoxylin-eosin and Ziehl-Neelsen-Faraco stains. Thus, immunohistochemical techniques using immunoperoxidase assay were performed for: anti-BCG, anti-M. leprae, anti-CD8, anti-CD3, anti-CD20, anti-S100, anti-CD1a, anti-CD68 and antivimentin. Spindle cells were present in all histoid patients. A pseudocapsule was observed in half of both studied forms. A comparison using the Ziehl-Neelsen-Faraco stain to evaluate anti-BCG and anti-M.leprae showed no major differences. The CD3+ cells were more pronounced in the histoid form than the lepromatous form. There was greater immunoreactivity toward CD8+ cells in the histoid form, as well as the CD20+ cell count. A similar count of S100+ cells in the epidermis of both leprosy forms was observed. There was a slight increase of dendritic cells in the histoid patients in the superficial and deep dermis. For CD1a marker, we observed expression in the epidermis and superficial dermis in both forms. A diffuse and intense infiltrate of CD68+ cells was also observed in the histoid and lepromatous forms. The high positivity for vimentin did not allow for a positive cell count. We concluded that the activation of both the cellular and humoral response is more pronounced in the histoid form because the T and B cells showed greater infiltration than those in the lepromatous form. The activation of dendritic and Langerhans cells is similar in both forms. The spindle cells likely belong to the macrophage population, thus maintaining phagocytic ability. The quantities of pseudocapsules and bacilli are similar and cannot serve as criteria for diagnosis.

Bacterial load in the nose and its correlation to the immune response in leprosy patients

Leprosy, whose etiologic agent is M. leprae, has its clinical manifestations correlated with distinct immunologic forms. The mechanism of infectivity and dissemination of the disease are not completely known, although the nasal mucosa is supposed to have an important role in pathogenesis. To correlate the clinical and bacteriological parameters with that of nasal biopsy and immunological tests, such as lepromin and ML-Flow results, in untreated leprosy patients. Two hundred and twenty-two patients were evaluated, clinically classified and subjected to skin smear, nasal biopsy, ML-Flow, and Mitsuda test. 689% of the cases were borderline cases. Nasal biopsy revealed 91.4% positivity in those who had specific antibodies against M. leprae on blood sample. Lepromatous leprosy cases were 100% positive on ML-flow test, had a large involvement in the nasal mucosa (91%), positive skin smears (100%) and negative Mitsuda test. Nasal bacillary index showed a good correlation with ML-Flow and had similar results when compared to skin smear. The tests agreement was good, revealing that nasal biopsy can be reliable in the diagnosis of multibacillary clinical forms and in the evaluation of the immunological status of leprosy patients. The presence of disseminated bacilli in the nasal mucosa was similar to skin involvement, when correlated with Mitsuda test and ML-Flow. As a result, the role of nasal bacillary index may play an important role in the clinical and immunologic characterization of leprosy patients.

Leprosy exposure, infection and disease: a 25-year surveillance study of leprosy patient contacts

Contact surveillance is a valuable strategy for controlling leprosy. A dynamic cohort study of leprosy contacts was initiated in 1987 at Oswaldo Cruz Foundation. The objective of this work was to review the data on the major risk factors leading up to the infectious stage of the disease, estimate incidence rates of leprosy in the cohort and characterise the risk factors for the disease among the contacts under surveillance. The incidence rate of leprosy among contacts of leprosy patients was estimated at 0.01694 cases per person-year in the first five years of follow-up. The following factors were associated with acquiring the disease: (i) not receiving the BCG vaccine, (ii) a negative Mitsuda reaction and (iii) contact with a patient with a multibacillary clinical form of leprosy. The contacts of index patients who had high bacilloscopic index scores > 1 were at especially high risk of infection. The following factors were associated with infection, which was defined as a seropositive reaction for anti-phenolic glicolipid-1 IgM: (i) young age (< 20 years), (ii) a low measured Mitsuda reaction (< 5 mm) and (iii) contact with an index patient who had a high bacilloscopic index. BCG vaccination and re-vaccination were shown to be protective among household contacts. The main conclusions of this study indicate an urgent need for additional leprosy control strategies in areas with a high incidence of the disease.

Serologic follow-up of IgG responses against recombinant mycobacterial proteins ML0405, ML2331 and LID-1 in a leprosy hyperendemic area in Venezuela

Leprosy is a slowly evolving disease that occurs mainly in adults. In this study, the Mamaría Village, state of Portuguesa was selected because it had one of the highest prevalence rates (13.25%) of leprosy cases in 1997. Between 1998-2004, 20.2% of the 89 cases registered in this village were less than 15 years old and 61.8% were males. Paucibacillary (PB) lesions were the predominant clinical forms identified, although also multibacillary (MB) forms were found. Additionally, 76% of the patients were bacteriologically negative. At the time of diagnosis, 75% of the patients presented with grade 0 disabilities, 23% with grade 1 and 2% with grade 2. Serum samples were collected from 18 PB and 15 MB patients, in addition to 14 family contacts, at the beginning and end of treatment. All the groups were re-evaluated during a three-year period (2008-2011). The proteins used for evaluation were ML0405, ML2331 and LID-1. These mycobacterial proteins were highly specific for Mycobacterium leprae and the IgG responses decreased in both MB and PB patients during multidrug treatment. Our results suggest that these antigens could be used as markers for successful treatment of non-reactional lepromatous patients.

Expression of sheep interleukin 23 (IL23A, alpha subunit p19) in two distinct gastrointestinal diseases

This paper reports the sequence of sheep interleukin 23A (p19), and shows that it shares 98% identity with bovine IL23A, 85% with human and 76% with mouse IL23A. It also reports the existence of two allelic variants that differ largely within the region encoding the amino terminal polypeptide signal sequence. An optimized RT-qPCR assay was used to quantify IL23A transcripts in sheep infected with two common gastrointestinal pathogens, the intracellular bacterium Mycobacterium avium subspecies paratuberculosis and the parasitic nematode Teladorsagia circumcincta. No differential expression of IL23A was detected in the mesenteric lymph node of sheep with the different pathogenic forms of paratuberculosis, however significantly high levels of IL23A were detected in the ileal mucosa of the paucibacillary form in comparison with the asymptomatic or multibacillary forms. Similarly, significantly high levels were present in the gastric lymph node draining T. circumcincta-infected abomasum in susceptible sheep. High levels of IL23A seem to be associated with lymphocytic infiltration and inflammation in both diseases but not with the macrophage infiltrate of multibacillary paratuberculosis.

Epidemiological Profile of Leprosy in the Brazilian state of Piauí between 2003 and 2008

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is considered a major public health issue in developing countries. To evaluate the clinical and epidemiological profile of leprosy patients between 2003 and 2008 in the state of Piauí, to analyze detection and prevalence rates in the general population and in the population of children under 15 years of age, and to evaluate the predominant clinical forms. Data were obtained from the notifiable diseases database of the State Health Department, Piauí, Brazil. Medical records are retrieved from patients' charts using a specific questionnaire and the collected data is then entered into the database system. Of the 12,238 cases of leprosy reported in this period, 85% represented new cases. The mean overall annual detection rate was 54 cases/100,000 habitants. The rate for children under 15 years of age was 15.3 cases/100,000 habitants. Overall, 52.18% of the patients were male; 64.66% were between 20 and 59 years of age; and 53.53% had the paucibacillary form of leprosy. Nevertheless, in 88.82% of cases of the paucibacillary form of the disease, more than five lesions were present, while in 10.55% of cases of the multibacillary form of the disease, no lesions were present. Over 20% of patients had some degree of disability. These indicators point to a high circulation of bacilli in the community and highlight the extreme difficulty experienced by the primary healthcare network in organizing itself in order to ensure that patients with this complex disease receive an accurate and early diagnosis.