The Impact of Vitamin A Deficiency on Tuberculosis Progression

BACKGROUND: Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression. METHODS: We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of dietary vitamin A deficiency. RESULTS: Among 773 participants, 96 developed incident TB during follow-up, 62.5% (60) of whom had stored serum samples obtained 90-365 days before TB diagnosis. In age- and sex- adjusted and multivariate analyses, respectively, incident TB cases were 3.99 times (95% confidence interval [CI], 2.41 to 6.60) and 3.59 times (95% CI, 2.05 to 6.29) more likely to have been vitamin A deficient than matched controls. Vitamin A-deficient guinea pigs manifested more extensive pulmonary pathology, atypical granuloma morphology, and increased bacterial growth after experimental TB infection. Reintroduction of dietary vitamin A to deficient guinea pigs after established TB disease successfully abrogated severe disease manifestations and altered cellular immune profiles. CONCLUSIONS: Human and animal studies support the role of baseline vitamin A deficiency as a determinant of future TB disease progression

Differential immunoglobulin and complement levels in leprosy prior to development of reversal reaction and erythema nodosum leprosum

Background Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. Methodology/findings We followed newly diagnosed multibacillary leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. Conclusions Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions

Human migration, railways and the geographic distribution of leprosy in Rio Grande do Norte State – Brazil

Submitted by Sandra Infurna ([email protected]) on 2018-01-02T15:15:30Z No. of bitstreams: 1 euzenir_sarno_etal_IOC_2016.pdf: 492103 bytes, checksum: 5fcef27563a5e2d28f729b36993f6fd9 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-01-02T15:32:52Z (GMT) No. of bitstreams: 1 euzenir_sarno_etal_IOC_2016.pdf: 492103 bytes, checksum: 5fcef27563a5e2d28f729b36993f6fd9 (MD5)Made available in DSpace on 2018-01-02T15:32:52Z (GMT). No. of bitstreams: 1 euzenir_sarno_etal_IOC_2016.pdf: 492103 bytes, checksum: 5fcef27563a5e2d28f729b36993f6fd9 (MD5) Previous issue date: 2015Hospital Giselda Trigueiro. Natal, RN, Brasil / Universidade Federal do Rio Grande do Norte. Instituto de Medicina Tropical do Rio Grande do Norte. Natal, RN, Brasil /Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Pós-Graduação em Medicina Tropical. Rio de |Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Norte. Instituto de Medicina Tropical do Rio Grande do Norte. Natal, RN, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Pós-Graduação em Medicina Tropical. Rio de |Janeiro, RJ, Brasil./ Weill Cornell Medical College. Division of Infectious Diseases and Center for Global Health. New York, NY, USA.Universidade Federal do Rio Grande do Norte. Departamento de Arquitetura. Natal, RN, Brasil.Instituto Nacional de Seguridade Social. Mossoró, RN, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio Grande do Norte. Instituto de Medicina Tropical do Rio Grande do Norte. Natal, RN, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT/DT). Salvador, BA, Brasil.Introduction—Leprosy is a public health problem in Brazil where 31,044 new cases were detected in 2013. Rio Grande do Norte is a small Brazilian state with a rate of leprosy lower than other areas in the same region, for unknown reasons. Objectives—We present here a review based on the analysis of a database of registered leprosy cases in Rio Grande do Norte state, comparing leprosy's geographic distribution among municipalities with local socio-economic and public health indicators and with historical documents about human migration in this Brazilian region. Results—The current distribution of leprosy in Rio Grande do Norte did not show correlation with socio-economic or public health indicators at the municipal level, but it appears related to economically emerging municipalities 100 years ago, with spread facilitated by railroads and train stations. Drought-related migratory movements which occurred from this state to leprosy endemic areas within the same period may be involved in the introduction of leprosy and with its present distribution within Rio Grande do Norte

Multibacillary leprosy by population groups in Brazil: Lessons from an observational study

<div><p>Background</p><p>Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by <i>Mycobacterium leprae</i>, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control.</p><p>Methods</p><p>A national databank of cases reported in Brazil (2001–2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads.</p><p>Results</p><p>A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65–69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33–2.38; OR = 1.99, CI95% = 1.96–2.02, respectively). Bacillary load was higher in male and in patients aged 20–39 and 40–59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country.</p><p>Conclusion</p><p>Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce <i>M</i>. <i>leprae</i> transmission.</p></div

Mean new case detection rates (NCDR) of leprosy in Brazil (2001–2013).

<p>3a) NCDR by sex according to age group. 3b) NCDR by sex and operational classification according to age group. MB: multibacillary, PB: paucibacillary.</p

Annual indicators for leprosy in Brazil (2001–2013)

<p>Annual indicators for leprosy in Brazil (2001–2013)</p