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      Interruption and Defaulting of Multidrug Therapy against Leprosy: Population-Based Study in Brazil's Savannah Region

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          Abstract

          Background

          Low adherence to multidrug therapy against leprosy (MDT) is still an important obstacle of disease control, and may lead to remaining sources of infection, incomplete cure, irreversible complications, and multidrug resistance.

          Methodology/Principal Finding

          We performed a population-based study in 78 municipalities in Tocantins State, central Brazil, and applied structured questionnaires on leprosy-affected individuals. We used two outcomes for assessment of risk factors: defaulting (not presenting to health care center for supervised treatment for >12 months); and interruption of MDT. In total, 28/936 (3.0%) patients defaulted, and 147/806 (18.2%) interrupted MDT. Defaulting was significantly associated with: low number of rooms per household (OR = 3.43; 0.98–9.69; p = 0.03); moving to another residence after diagnosis (OR = 2.90; 0.95–5.28; p = 0.04); and low family income (OR = 2.42; 1.02–5.63: p = 0.04). Interruption of treatment was associated with: low number of rooms per household (OR = 1.95; 0.98–3.70; p = 0.04); difficulty in swallowing MDT drugs (OR = 1.66; 1.03–2.63; p = 0.02); temporal non-availability of MDT at the health center (OR = 1.67; 1.11–2.46; p = 0.01); and moving to another residence (OR = 1.58; 95% confidence interval: 1.03–2.40; p = 0.03). Logistic regression identified temporal non-availability of MDT as an independent risk factor for treatment interruption (adjusted OR = 1.56; 1.05–2.33; p = 0.03), and residence size as a protective factor (adjusted OR = 0.89 per additional number of rooms; 0.80–0.99; p = 0.03). Residence size was also independently associated with defaulting (adjusted OR = 0.67; 0.52–0.88; p = 0.003).

          Conclusions

          Defaulting and interruption of MDT are associated with some poverty-related variables such as family income, household size, and migration. Intermittent problems of drug supply need to be resolved, mainly on the municipality level. MDT producers should consider oral drug formulations that may be more easily accepted by patients. Thus, an integrated approach is needed for further improving control, focusing on vulnerable population groups and the local health system.

          Author Summary

          Leprosy is still a public health problem in Brazil, and low adherence to multidrug therapy against leprosy (MDT) is an important obstacle of disease control. This may lead to remaining sources of infection, incomplete cure, complications, and multidrug resistance. We performed a study in 78 municipalities in central Brazil, and interviewed leprosy-affected individuals. In total, 3% of patients defaulted, and 18.2% interrupted MDT. Risk factors for interruption of treatment include: reduced number of rooms per household (OR = 1.95; p = 0.04); difficulty in swallowing MDT drugs (OR = 1.66; p = 0.02); temporal non-availability of MDT drugs at health center (OR = 1.67; p = 0.01); and moving residence after diagnosis (OR = 1.58; p = 0.03). Defaulting MDT was significantly associated with: reduced number of rooms per household (OR = 3.43; p = 0.03); moving to another residence (OR = 2.90; p = 0.04); and low family income (OR = 2.42; p = 0.04). Our study shows that defaulting and interruption of MDT against leprosy are associated with some poverty-related variables such as family income, household size, and migration. Intermittent problems of drug supply need to be resolved, mainly on the municipality level. MDT producers should consider drug formulations that are more easily accepted by patients. An integrated approach is needed for further improving control, focusing on most vulnerable population groups and the local health system.

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          Most cited references35

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          Socioeconomic, environmental, and behavioural risk factors for leprosy in North-east Brazil: results of a case-control study.

          Brazil reports almost 80% of all leprosy cases in the Americas. This study aimed to identify socioeconomic, environmental, and behavioural factors associated with risk of leprosy occurrence in the endemic North-eastern region. A case-control study in four municipalities. cases of leprosy diagnosed in the previous 2 years, with no other known, current, or past case of leprosy in the household or in the neighbourhood. individuals presenting for reasons other than skin problems to the health unit where the case was diagnosed and who lived in the same municipality as the case with whom it was matched. For each case four controls were selected. A semi-structured questionnaire was used to collect demographic, socioeconomic, environmental, and behavioural data. A multivariate hierarchical analysis was performed according to a previously defined framework. 226 cases and 857 controls were examined. Low education level, ever having experienced food shortage, bathing weekly in open water bodies (creek, river and/or lake) 10 years previously, and a low frequency of changing bed linen or hammock (>or=biweekly) currently were all significantly associated with leprosy. Having a BCG vaccination scar was found to be a highly significant protective factor. Except for BCG vaccination, variables that remained significant in the hierarchical analysis are cultural or linked to poverty. They may act on different levels of the transmission of Mycobacterium leprae and/or the progress from infection to disease. These findings give credit to the hypothesis that person-to-person is not the only form of M. leprae transmission, and that indirect transmission might occur, and other reservoirs should exist outside the human body.
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            Defaulting from DOTS and its determinants in three districts of Arsi Zone in Ethiopia.

            Three districts of Oromia Region in Arzi Zone, Ethiopia. To determine the rate of defaulting from directly observed treatment, short course (DOTS) for tuberculosis and identify associated factors. A case control study. Records of 1367 new tuberculosis patients put on DOTS during a period of 30 months (1 July 1997-31 December 1999) were reviewed to determine the defaulting rate. Cases were defaulters and controls were selected by paired matching of sex and age using the lottery method. All study subjects were actively traced and interviewed by trained interviewers using a pre-tested structured questionnaire. The overall rate of defaulting from DOTS was calculated to be 11.3%, while the rate in sputum smear-positive cases was 11.6%. Defaulting was highest (81%) during the continuation phase of treatment. Medication side effects were significantly associated with defaulting (OR = 4.20, 95% CI 1.51-11.66), while adequate knowledge and family support were found to be possible protective factors (OR = 0.04, 95% CI 0.02-0.1 and OR = 0.19, 95% CI 0.08-0.46, respectively). Major factors contributing to high rates of defaulting were found to be lack of family support, inadequate knowledge about treatment duration and medication side effects. Control programmes that take these factors into consideration should be successful in reducing defaulting.
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              The epidemiological behaviour of leprosy in Brazil.

              The elimination strategy reduced known leprosy prevalence but the detection rate remains high in many countries, including Brazil. The high Brazilian detection rate imposes a limit to the reduction of known prevalence in the short term. The knowledge of time behaviour and spatial distribution of leprosy statistics will contribute to decision making for leprosy control. The numbers of newly diagnosed leprosy cases by region and year from 1980 to 2004, and prevalent cases from 1990 to 2007 were fitted as a parabolic function of time in negative binomial regression models. To detect areas with increased leprosy detection rates we used spatial scan statistics for cases detected from 2005 to 2007 in the three regions where leprosy is still a public health problem. All detection rate series except the one for the south region showed statistically significant regression coefficients for time and time squared, showing an initial increasing trend. Scan statistics detected 29 statistically significant spatial clusters. These clusters cover 789 municipalities with a total of 51,904 cases detected. Time behaviour of the detection rate is probably a result of better access to primary health care. According to spatial scan statistics, Brazil can be divided into highly endemic areas, containing 11.2% of the total Brazilian population, with a mean detection rate in 2007 of 76.4 per 100,000 inhabitants, and areas of much lower endemicity, containing 888% of the population with a mean detection rate of 132. Leprosy is concentrated in a small proportion of the Brazilian population.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                May 2011
                3 May 2011
                : 5
                : 5
                : e1031
                Affiliations
                [1 ]Department of Community Health, School of Medicine, Federal University of Ceará, Fortaleza, Brazil
                [2 ]Anton Breinl Centre for Public Health and Tropical Medicine, School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Australia
                [3 ]School of Medicine, University of Düsseldorf, Düsseldorf, Germany
                [4 ]School of Medicine, University of Cologne, Cologne, Germany
                [5 ]State Leprosy Control Program, State Health Secretariat of Tocantins, Palmas, Brazil
                Emory University, United States of America
                Author notes

                Conceived and designed the experiments: JH LA CHMA ANR ACF. Performed the experiments: LA CHMA OAC ARO KH FW. Analyzed the data: JH LA OAC. Wrote the paper: JH LA CHMA ANR ACF.

                Article
                PNTD-D-10-00222
                10.1371/journal.pntd.0001031
                3086809
                21572523
                885bbf5f-2141-40e4-99aa-c03f3da08a56
                Heukelbach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 29 November 2010
                : 28 February 2011
                Page count
                Pages: 9
                Categories
                Research Article
                Medicine
                Epidemiology
                Infectious Disease Epidemiology
                Infectious Diseases
                Neglected Tropical Diseases
                Leprosy
                Infectious Disease Control
                Public Health

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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