A profile of patients treated at a national leprosy outpatient referral clinic in Rio de Janeiro, Brazil, 1986-2007.

OBJECTIVE: To analyze a profile of patients treated at a national leprosy outpatient referral clinic in metropolitan Rio de Janeiro, Brazil, over a period of more than two decades, and the subgroup of nationally registered leprosy cases from the same residential area, as well as all registered cases statewide. METHODS: An observational, descriptive analysis was carried out for patients treated from 1986 to 2007 at the Souza Araújo Outpatient Clinic (Ambulatório Souza Araújo, ASA), a national referral center for the diagnosis and treatment of leprosy at the Oswaldo Cruz Foundation (Fiocruz) that serves clients from the city of Rio de Janeiro and other municipalities in the metropolitan area of Rio de Janeiro State. Demographic and clinical data for the subgroup of leprosy cases registered with Brazil's National Disease Notification System (Sistema Nacional de Informação de Agravos de Notificação, SINAN) between 2001 and 2007 and residing in the same municipalities as the ASA patients, and for all registered cases statewide, were also analyzed. RESULTS: Among the ASA patients, there was a decrease in average family income (from 3.9 to 2.7 times the minimum salary between the periods 1998-2002 and 2003-2007); the proportion of multibacillary (MB) patients (from 52.7% to 46.9%); and the proportion of patients younger than 15 years old (from 12.8% to 8.7%). Among the MB patients, the average initial and final bacilloscopic indices were significantly higher in 2003-2007. Compared with the SINAN cases, more ASA cases involved disability and were younger than 15 years old. CONCLUSIONS: Patients living with leprosy in the metropolitan area of the state of Rio de Janeiro belong to the most deprived social strata and have not benefited from the overall improvement in socioeconomic conditions in Brazil.

Microfasciculation: a morphological pattern in leprosy nerve damage.

AIMS: To study Microfasciculation, a perineurial response found in neuropathies, emphasizing its frequency, detailed morphological characteristics and biological significance in pure neural leprosy (PNL), post-treatment leprosy neuropathy (PTLN) and non-leprosy neuropathies (NLN). METHODS AND RESULTS: Morphological characteristics of microfascicles were examined via histological staining methods, immunohistochemical expression of neural markers and transmission electronmicroscopy. The detection of microfasciculation in 18 nerve biopsy specimens [12 PNL, six PTLN but not in the NLN group, was associated strongly with perineurial damage and the presence of a multibacillary inflammatory process in the nerves, particularly in the perineurium. Immunoreactivity to anti-S100 protein, anti-neurofilament, anti-nerve growth receptor and anti-myelin basic protein immunoreactivity was found within microfascicles. Ultrastructural examination of three biopsies showed that fibroblast-perineurial cells were devoid of basement membrane despite perineurial-like NGFr immunoreactivity. Morphological evidence demonstrated that multipotent pericytes from inflammation-activated microvessels could be the origin of fibroblast-perineurial cells. CONCLUSIONS: A microfasciculation pattern was found in 10% of leprosy-affected nerves. The microfascicles were composed predominantly of unmyelinated fibres and denervated Schwann cells (SCs) surrounded by fibroblast-perineurial cells. This pattern was found more frequently in leprosy nerves with acid-fast bacilli (AFB) and perineurial damage while undergoing an inflammatory process. Further experimental studies are necessary to elucidate microfascicle formation.

Low rate of relapse after twelve-dose multidrug therapy for hansen's disease: A 20-year cohort study in a brazilian reference center.

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.

Poverty, bridging between injecting drug users and the general population, and "interiorization" may explain the spread of HIV in southern Brazil.

The aim of this paper is to study how structural determinants and the role of injecting drug users (IDUs) as a bridging population to the general population affected the AIDS subepidemic in southern Brazil during 1986-2000. Data from 288 southernmost Brazilian municipalities were analyzed. Using hierarchical modeling and inputs from a Geographic Information System, a multilevel model was constructed. The dependent variable was the logged AIDS standardized incidence rate (among the heterosexual population aged 15-69-years-old); independent variables included indicators for education, water provision, sewage, and garbage collection, per capita income, Gini coefficient (on income), Human Development Index, indicators of accessibility, and AIDS rate among IDUs. Significant predictors included AIDS rate among IDUs, distance from/to highways/railways, the Human Development Index and the ratio of residents who have access to sanitary installations. Poverty (as measured by socioeconomic indicators) and bridging from IDUs contribute to the spread of HIV/AIDS in Brazilian southern municipalities.

Quantitative polymerase chain reaction in paucibacillary leprosy diagnosis: A follow-up study.

OBJECTIVE: The diagnosis of paucibacillary (PB) leprosy cases remains a challenge because of the absence of a confirmatory laboratory method. While quantitative polymerase chain reaction (qPCR) has been shown to provide reliable sensitivity and specificity in PB diagnoses, a thorough investigation of its efficacy in clinical practice has not yet been published. The present study evaluated patients with suspected leprosy skin lesions by using qPCR to identify PB individuals in the Leprosy Outpatient clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. METHODS: One hundred seventy-two suspected PB cases were included in the study. The patients were evaluated by a dermatologist at three different times. The clinical dermato-neurological examination and collected samples were performed on the first visit. On the second visit, the results of the histopathological analysis and PCR assay (DNA-based Mycobacterium leprae qPCR-targeting 16S gene) results were analyzed, and a decision regarding multi-drug therapy was made. A year later, the patients were re-examined, and the consensus diagnosis was established. RESULTS: In 58% (100/172) of cases, a conclusive diagnosis via histopathological analysis was not possible; however, 30% (30/100) of these cases had a positive PCR. One hundred ten patients (110/172) attended the third visit. The analysis showed that while the sensitivity of the histopathological test was very low (35%), a qPCR alone was more effective for identifying leprosy, with 57% sensitivity. CONCLUSION: The use of qPCR in suspected PB cases with an inconclusive histology improved the sensitivity of leprosy diagnoses.

Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011-2018.

Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6-290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.

[Signs and symptoms associated with sexually transmitted infections in Brazil, 2005]. / Sinais e sintomas associados às doenças sexualmente transmissíveis no Brasil, 2005.

OBJECTIVE: Sexually transmitted infections (STIs) are a major determinant of population disease burden worldwide. The objective of the study was to assess self-reported morbidity associated to STIs according to gender. METHODS: The study data were obtained from a 2005 study consisting of a multistage probabilistic sample of 5,040 respondents, aged 16-65 years, living in urban areas in Brazil. These data were compared with those from a previous 1998 study. Bivariate analyses were carried out using Pearson's chi-square test and simple linear regression followed by logistic regression. RESULTS: In both men and women, the variables: previous HIV testing, personal belief in unfaithful love, and number of sexual partners in a lifetime were significantly associated to STIs. In women only, the covariates: low family income, living in the Center-West, Southeast and South regions, and reporting of physical violence were independently associated to STIs. In men, the variables associated were: age group (35 years or more), living in the South region and in the state of São Paulo, and self-perceived HIV infection risk. CONCLUSIONS: Signs and symptoms associated to STIs have strong gender differences in the general population and education interventions should be specifically targeted to either men or women.

[Drug and alcohol use: main findings of a national survey, Brazil 2005]. / Consumo de álcool e drogas: principais achados de pesquisa de âmbito nacional, Brasil 2005.

OBJECTIVE: To assess alcohol and drug use in a representative sample of the urban Brazilian population and their correlation with sexual and reproductive health. METHODS: Data from a national population-based survey with a complex sampling, performed in 2005 was used. A total of 5,040 individuals from both genders, in the age group from 16 to 65 years old, were interviewed. Issues regarding drug and alcohol use and sexual behavior were assessed. Bivariate and multivariate analyses were used. RESULTS: Alcohol was the most frequently used substance, with reports of regular use in the lives of 18% of interviewees. Use of illegal drugs was mentioned by 9% of the interviewees especially marijuana and snorted cocaine; injected drugs use was not frequent. There was a decrease in snorted cocaine use and an increase in marijuana use (in the last 12 months), compared to results of a similar survey conducted in 1998. History of sexual abuse was a risk factor for drug use and regular alcohol use. Interviewees mentioning the role of religion in their background, being White, and female were less likely to use alcohol in a regular way, which is especially prevalent among elderly males.Leisure activities and absence of current religious practice were associated with drug use. CONCLUSIONS: The regular or irregular alcohol use is prevalent in the urban Brazilian population, whereas injected drug use is rare. Over the last decade there was a decline in cocaine use. A history of sexual abuse was central to later use of alcohol and drugs.

The first ten years: achievements and challenges of the Brazilian program of universal access to HIV/AIDS comprehensive management and care, 1996-2006.

A review was carried out of papers published between 1996 and 2006, documenting the introduction of highly active anti-retroviral therapy (HAART) in Brazil. Papers indexed in the MEDLINE and SciELO databases were retrieved using different combinations of keywords related to the management and care of AIDS in the post-HAART era: opportunistic diseases and co-infections, adherence to therapy, survival in the pre- and post-HAART eras, adverse events and side-effects, emergence and possible transmission of resistant viral strains, metabolic and cardiovascular disorders, and issues related to access to care and equity. The review documents the dramatic changes in HIV/AIDS disease progression in the post-HAART era, including an increase in survival and quality of life and a pronounced decrease in the episodes of opportunistic diseases. Notwithstanding such major achievements, new challenges have emerged, including slow evolving co-infections (such as hepatitis C, metabolic and cardiovascular disorders), the emergence of viral resistance, with consequences at the individual level (virological failure) and the community level (primary/secondary resistance at the population level), and impacts on the cost of new therapeutic regimens.

Reconstructing the AIDS epidemic among injection drug users in Brazil.

The HIV/AIDS epidemic among injection drug users (IDUs) in Brazil has been unique in terms of temporal and geographical contrasts. This analysis explores these contrasts through the use of multilevel modeling. Standardized AIDS incidence rates among IDUs for Brazilian municipalities (1986-2000) were used as the dependent variable, with a set of social indicators as independent variables (covariates). In some States of the North/Northeast, the epidemic among IDUs has been incipient. The São Paulo epidemic extended to reach a network of municipalities, most of which located far from the capital. More recently, on a smaller scale, a similar extension has been observed in the southernmost States of the country. Both "number of physicians per inhabitant" and "standard distance to the State capital" were found to be associated with AIDS incidence. AIDS cases among IDUs appeared to cluster in wealthier, more developed municipalities. The relative weight of such extensive dissemination in key, heavily populated States prevails in the Brazilian IDU epidemic, defining a central-western-southeastern strip of wealthier middle-sized municipalities and more recently a southern strip of municipalities deeply affected by the epidemic in this population.

"The first shot": the context of first injection of illicit drugs, ongoing injecting practices, and hepatitis C infection in Rio de Janeiro, Brazil.

The context of first drug injection and its association with ongoing injecting practices and HCV (hepatitis C virus) infection were investigated. Injection drug users (IDUs) (N = 606) were recruited in "drug scenes" (public places, bars) in Rio de Janeiro, Brazil, interviewed, and tested for HCV. Sharing of needles/syringes was more prevalent at the first injection (51.3%) than at the baseline interview (36.8%). Those who shared syringes/needles at first injection were more likely to be currently engaged in direct/indirect sharing practices. Among young injectors (< 30 years), those reporting sharing of needles/ syringes at the first injection were about four times more likely to have been infected by HCV. Hepatitis C virus prevalence among active IDUs (n = 272) was 11%. Prison history and longer duration of drug injection were identified as independent predictors of HCV infection. To effectively curb HCV transmission among IDUs and minimize harms associated with risk behaviors, preventive strategies should target individuals initiating drug injection beginning with their very first injection and discourage the transition from non-injecting use to the self-injection of illicit drugs.

[Brazilian biomedical and epidemiological research vis-à-vis the UNGASS targets]. / Pesquisas brasileiras biomédicas e epidemiológicas face às metas da UNGASS.

The focus of the present study is the Brazilian response within science, technology and innovation to the targets formulated in the UNGASS document. An analysis was made of items 70-73 of the UNGASS Draft Declaration of Commitment on HIV/AIDS (2001), which defined science, technology and innovation targets relating to HIV/AIDS. The main topics listed in these items were put into operation in the form of keywords, in order to guide systematic searches within the standard biomedicine databases, also including the subdivisions of the Web of Science relating to natural and social sciences. The success of Brazilian research within the field of characterization and isolation of HIV-1 is undeniable. Phase II/III vaccine studies have been developed in Rio de Janeiro, Belo Horizonte and São Paulo. Empirical studies on the monitoring of primary resistance have been developed in specific populations, through the Brazilian HIV Resistance Monitoring Network. Within the field of monitoring secondary resistance, initiatives such as the National Genotyping Network have been highlighted. Two national systems--the Mortality Information System and the Notifiable Diseases Information System (Aids)--and some studies with wider coverage have given rise to work on trends within the epidemic. The production of high-quality generic medications and their free distribution to patients have been highlighted. Brazil has implemented a consistent and diversified response within the field of HIV/AIDS, with studies relating to the development of vaccines, new medications and monitoring of the epidemic.

[Brazilian psychosocial and operational research vis-à-vis the UNGASS targets]. / Pesquisas brasileiras psicossociais e operacionais face às metas da UNGASS.

Items from the UNGASS Draft Declaration of Commitment on HIV/AIDS (2001) are analyzed. The Brazilian experience of new methods for testing and counseling among vulnerable populations, preventive methods controlled by women, prevention, psychosocial support for people living with HIV/AIDS, and mother-child transmission, is discussed. These items were put into operation in the form of keywords, in systematic searches within the standard biomedicine databases, also including the subdivisions of the Web of Science relating to natural and social sciences. The Brazilian experience relating to testing and counseling strategies has been consolidated through the utilization of algorithms aimed at estimating incidence rates and identifying recently infected individuals, testing and counseling for pregnant women, and application of quick tests. The introduction of alternative methods and new technologies for collecting data from vulnerable populations has been allowing speedy monitoring of the epidemic. Psychosocial support assessments for people living with HIV/AIDS have gained impetus in Brazil, probably as a result of increased survival and quality of life among these individuals. Substantial advances in controlling mother-child transmission have been observed. This is one of the most important victories within the field of HIV/AIDS in Brazil, but deficiencies in prenatal care still constitute a challenge. With regard to prevention methods for women, Brazil has only shown a halting response. Widespread implementation of new technologies for data gathering and management depends on investments in infrastructure and professional skills acquisition.

HIV-1 infection among injection and ex-injection drug users from Rio de Janeiro, Brazil: prevalence, estimated incidence and genetic diversity.

BACKGROUND AND OBJECTIVES: Due to their behavioral conditions and vulnerability, injection drug users (IDUs) are prone to multiple simultaneous or sequential infections with distinct HIV-1 subtypes and variants, making them a key population for molecular epidemiology surveillance. In the present study, we evaluated HIV-1 infection seroprevalence, genetic diversity and estimated incidence among IDUs and ex-injection drug users (ex-IDUs) from Rio de Janeiro, Brazil. STUDY DESIGN: Six hundred and eight IDUs and ex-IDUs, recruited between 1999 and 2001, were interviewed and agreed to donate 30 ml of blood. The serologic status for HIV infection was determined by two ELISAs and confirmed by IFA. CD4+ T-cell percentages were assessed by flow cytometry. HIV-1 positive samples were submitted to viral load quantification. DNA samples were PCR amplified and HIV-1 subtypes were determined using env and gag HMA. RESULTS AND CONCLUSIONS: Forty-eight (7.89%) individuals were seropositive for HIV-1 infection. The seroincidence of HIV-1 infection was estimated as 0.76%. HIV-1 env and gag subtyping identified 29 (69%) samples as belonging to subtype B, 7 (16.7%) to subtype F, and 6 (14.3%) discordant env/gag genomes infections, indicating the circulation of recombinant viruses in this population.

Epidemiological and clinical patterns of 92 patients co-infected with HIV and Mycobacterium leprae from Rio de Janeiro State, Brazil.

BACKGROUND: Many articles have shown that HIV infection can modify the clinical course of leprosy, but very scant epidemiological and clinical data about this co-infection are available in the peer-reviewed literature. METHODS: We herein describe the geographical distribution and demographic characteristics of 92 HIV/Mycobacterium leprae co-infected patients assisted in a Brazilian Leprosy referral center. A multivariate analysis was performed in order to establish clinical factors associated with type 1 reaction. RESULTS: Co-infected patient admissions have steadily increased over the last years at this referral center. Most patients were men, with a mean age of 32.3 years and presenting with the paucibacillary form of leprosy. The use of antiretroviral therapy (ART) was the only factor associated with type 1 reaction. Most patients were living in the metropolitan area and the north sub area of Rio de Janeiro City. CONCLUSION: Co-infected patients receiving ART have a greater chance to develop type 1 reaction. Patients living with both HIV and leprosy are likely to live in regions characterized by a high density impoverished population.

A whole blood assay as a simple, broad assessment of cytokines and chemokines to evaluate human immune responses to Mycobacterium tuberculosis antigens.

In vitro stimulation of whole blood or isolated peripheral blood cells with specific antigens is used for several purposes. We sought to identify a reliable, reproducible, fast and feasible in vitro method to assess human cellular immune responses to Mycobacterium tuberculosis. In contrast to peripheral blood mononuclear cell (PBMC) culture, a whole blood assay (WBA) provides a more physiological environment, which may provide a broader assessment of serum biomarker, biosignature profiles. Twenty-three asymptomatic individuals with M. tuberculosis infection were recruited. Total cells from the WBA (diluted 1:3 in completed RPMI) and PBMC (2×10(5)cells/ml) plus M. tuberculosis Ag85A, Ag85B, ESAT-6 and Mycobacterium bovis 65kDa were characterized by flow cytometry, then added in 96-well plates and on day 5 plasma and supernatants were harvested for detection of 17 cytokines by a Luminex array system. There was agreement between PBMC and WBA for IL-2, IL-5, IL-6, IL-7, IL-13, IFN-γ, TNF-α, MCP-1 and MIP-1ß. There was evidence toward higher IL-10 (p≤0.049) and G-CSF (p≤0.012) plasma production, and higher IL-1ß (p≤0.048), IL-4 (p≤0.044), IL-12p70 (p≤0.006), IL-17 (p≤0.002) and GM-CSF (p≤0.049) production for PBMC vs. WBA. Both methods provided virtually no reaction to the internal, negative control. Due to technical issues linked to data out of range, IL-8 data were not considered. These results suggest that, depending on the method employed, PBMC and/or WBA techniques provide fine conditions for the model proposed and thus whole blood cultures are well-suited low-cost proxy-measures during search for serum biomarkers.

Progression of leprosy neuropathy: a case series study.

A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed with 10 paucibacillary (PB) and 12 multibacillary (MB) patients evaluated at diagnosis and one year after cessation of multidrug therapy (MDT). Peripheral nerve function was assessed clinically and by means of the sympathetic skin response, skin vasomotor reflex, and nerve conduction study (NCS). At diagnosis, 73% of the total 22 patients had nerve function impairment (NFI). Autonomic function (χ(2)= 5.5, P= 0.019) and NCS (χ(2)= 7.765, P= 0.01) were significantly more altered in MB than PB patients. At final evaluation, NFI of the MB patients had worsened, especially among the six who had leprosy reaction. As the NFI of PB patients showed improvement, a significant difference between the two groups (χ(2)= 12.320, P= 0.001) was observed. A high prevalence of neuropathy was observed in newly diagnosed patients. Associating different tests with a thorough clinical neurological evaluation increases detection rates.

Pathogen-specific epitopes as epidemiological tools for defining the magnitude of Mycobacterium leprae transmission in areas endemic for leprosy.

During recent years, comparative genomic analysis has allowed the identification of Mycobacterium leprae-specific genes with potential application for the diagnosis of leprosy. In a previous study, 58 synthetic peptides derived from these sequences were tested for their ability to induce production of IFN-γ in PBMC from endemic controls (EC) with unknown exposure to M. leprae, household contacts of leprosy patients and patients, indicating the potential of these synthetic peptides for the diagnosis of sub- or preclinical forms of leprosy. In the present study, the patterns of IFN-γ release of the individuals exposed or non-exposed to M. leprae were compared using an Artificial Neural Network algorithm, and the most promising M. leprae peptides for the identification of exposed people were selected. This subset of M. leprae-specific peptides allowed the differentiation of groups of individuals from sites hyperendemic for leprosy versus those from areas with lower level detection rates. A progressive reduction in the IFN-γ levels in response to the peptides was seen when contacts of multibacillary (MB) patients were compared to other less exposed groups, suggesting a down modulation of IFN-γ production with an increase in bacillary load or exposure to M. leprae. The data generated indicate that an IFN-γ assay based on these peptides applied individually or as a pool can be used as a new tool for predicting the magnitude of M. leprae transmission in a given population.

Leprosy among patient contacts: a multilevel study of risk factors.

BACKGROUND: This study aimed to evaluate the risk factors associated with developing leprosy among the contacts of newly-diagnosed leprosy patients. METHODOLOGY/PRINCIPAL FINDINGS: A total of 6,158 contacts and 1,201 leprosy patients of the cohort who were diagnosed and treated at the Leprosy Laboratory of Fiocruz from 1987 to 2007 were included. The contact variables analyzed were sex; age; educational and income levels; blood relationship, if any, to the index case; household or non-household relationship; length of time of close association with the index case; receipt of bacillus Calmette-Guérin (BGG) vaccine and presence of BCG scar. Index cases variables included sex, age, educational level, family size, bacillary load, and disability grade. Multilevel logistic regression with random intercept was applied. Among the co-prevalent cases, the leprosy-related variables that remained associated with leprosy included type of household contact, [odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.02, 1.73] and consanguinity with the index case, (OR = 1.89, 95% CI: 1.42-2.51). With respect to the index case variables, the factors associated with leprosy among contacts included up to 4 years of schooling and 4 to 10 years of schooling (OR = 2.72, 95% CI: 1.54-4.79 and 2.40, 95% CI: 1.30-4.42, respectively) and bacillary load, which increased the chance of leprosy among multibacillary contacts for those with a bacillary index of one to three and greater than three (OR = 1.79, 95% CI: 1.19-2.17 and OR: 4.07-95% CI: 2.73, 6.09), respectively. Among incident cases, household exposure was associated with leprosy (OR = 1.96, 95% CI: 1.29-2.98), compared with non-household exposure. Among the index case risk factors, an elevated bacillary load was the only variable associated with leprosy in the contacts. CONCLUSIONS/SIGNIFICANCE: Biological and social factors appear to be associated with leprosy among co-prevalent cases, whereas the factors related to the infectious load and proximity with the index case were associated with leprosy that appeared in the incident cases during follow-up.

Genotyping did not evidence any contribution of Mycobacterium bovis to human tuberculosis in Brazil.

The contribution of Mycobacterium bovis to the global burden of tuberculosis (TB) in man is likely to be underestimated due to its dysgonic growth characteristics and because of the absence of pyruvate in most used media is disadvantageous for its primary isolation. In Brazil Mycobacterium culture, identification and susceptibility tests are performed only in TB reference centers, usually for selected cases. Moreover, solid, egg-based, glycerol-containing (without pyruvate supplementation) Löwenstein-Jensen (L-J) or Ogawa media are routinely used, unfavouring M. bovis isolation. To determine the importance of M. bovis as a public health threat in Brazil we investigated 3046 suspected TB patients inoculating their clinical samples onto routine L-J and L-J pyruvate enriched media. A total of 1796 specimens were culture positive for Mycobacterium spp. and 702 TB cases were confirmed. Surprisingly we did not detect one single case of M. bovis in the resulting collection of 1674 isolates recovered from M. bovis favourable medium analyzed by conventional and molecular speciation methods. Also, bacillary DNA present on 454 sputum smears from 223 TB patients were OxyR genotyped and none was recognized as M. bovis. Our data indicate that M. bovis importance on the burden of human TB in Brazil is marginal.