Lisa Y. Armitige

Bio: Lisa Y. Armitige is an academic researcher from University of Texas Health Science Center at San Antonio. The author has contributed to research in topics: Adverse effect & Coinfection. The author has an hindex of 2, co-authored 2 publications receiving 20 citations.

Directly observed therapy for treating tuberculosis

Abstract: Background Tuberculosis (TB) requires at least six months of treatment. If treatment is incomplete, patients may not be cured and drug resistance may develop. Directly Observed Therapy (DOT) is a specific strategy, endorsed by the World Health Organization, to improve adherence by requiring health workers, community volunteers or family members to observe and record patients taking each dose. Objectives To evaluate DOT compared to self-administered therapy in people on treatment for active TB or on prophylaxis to prevent active disease. We also compared the effects of different forms of DOT. Search methods We searched the following databases up to 13 January 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS and mRCT. We also checked article reference lists and contacted relevant researchers and organizations. Selection criteria Randomized controlled trials (RCTs) and quasi-RCTs comparing DOT with routine self-administration of treatment or prophylaxis at home. Data collection and analysis Two review authors independently assessed risk of bias of each included trial and extracted data. We compared interventions using risk ratios (RR) with 95% confidence intervals (CI). We used a random-effects model if meta-analysis was appropriate but heterogeneity present (I2 statistic > 50%). We assessed the quality of the evidence using the GRADE approach. Main results Eleven trials including 5662 participants met the inclusion criteria. DOT was performed by a range of people (nurses, community health workers, family members or former TB patients) in a variety of settings (clinic, the patient's home or the home of a community volunteer). DOT versus self-administered Six trials from South Africa, Thailand, Taiwan, Pakistan and Australia compared DOT with self-administered therapy for treatment. Trials included DOT at home by family members, community health workers (who were usually supervised); DOT at home by health staff; and DOT at health facilities. TB cure was low with self-administration across all studies (range 41% to 67%), and direct observation did not substantially improve this (RR 1.08, 95% CI 0.91 to 1.27; five trials, 1645 participants, moderate quality evidence). In a subgroup analysis stratified by the frequency of contact between health services in the self-treatment arm, daily DOT may improve TB cure when compared to self-administered treatment where patients in the self-administered group only visited the clinic every month (RR 1.15, 95% CI 1.06 to 1.25; two trials, 900 participants); but with contact in the control becoming more frequent, this small effect was not apparent (every two weeks: RR 0.96, 95% CI 0.83 to 1.12; one trial, 497 participants; every week: RR 0.90, 95% CI 0.68 to 1.21; two trials, 248 participants). Treatment completion showed a similar pattern, ranging from 59% to 78% in the self-treatment groups, and direct observation did not improve this (RR 1.07, 95% CI 0.96 to 1.19; six trials, 1839 participants, moderate quality evidence). DOT at home versus DOT at health facility In four trials that compared DOT at home by family members, or community health workers, with DOT by health workers at a health facility there was little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.88 to 1.18, four trials, 1556 participants, moderate quality evidence; treatment completion: RR 1.04, 95% CI 0.91 to 1.17, three trials, 1029 participants, moderate quality evidence). DOT by family member versus DOT by community health worker Two trials compared DOT at home by family members with DOT at home by community health workers. There was also little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.86 to 1.21; two trials, 1493 participants, moderate quality evidence; completion: RR 1.05, 95% CI 0.90 to 1.22; two trials, 1493 participants, low quality evidence). Specific patient categories A trial of 300 intravenous drug users in the USA evaluated direct observation with no observation in TB prophylaxis to prevent active disease and showed little difference in treatment completion (RR 1.00, 95% CI 0.88 to 1.13; one trial, 300 participants, low quality evidence). Authors' conclusions From the existing trials, DOT did not provide a solution to poor adherence in TB treatment. Given the large resource and cost implications of DOT, policy makers might want to reconsider strategies that depend on direct observation. Other options might take into account financial and logistical barriers to care; approaches that motivate patients and staff; and defaulter follow-up.

Monkey Models of Tuberculosis: Lessons Learned

Abstract: The use of animal models has been invaluable for studying the pathogenesis of Mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research.

Tratamento da tuberculose

Abstract: O tratamento da tuberculose permanece um desafio em função da necessidade de que, em sua abordagem, seja considerado o contexto da saúde do indivíduo e da saúde coletiva. Adicionalmente, as questões sociais e econômicas têm-se mostrado como variáveis a ser consideradas na efetividade do tratamento. Ao revisarmos de forma crítica a literatura científica nacional e internacional sobre o tratamento da tuberculose nos últimos anos, tivemos como objetivos apresentar aos profissionais da área de saúde as recomendações baseadas na realidade brasileira e fornecer os subsídios necessários para a melhor tomada de decisão frente ao paciente com tuberculose, de modo a minimizar a morbidade e interromper a transmissão da doença Em função disso, o TDO é recomendado.

Non-Human Primate Models of Tuberculosis

Abstract: Among the animal models of tuberculosis (TB), the non-human primates, particularly rhesus macaques (Macaca fascicularis) and cynomolgus macaques (Macaca mulatta), share the greatest anatomical and physiological similarities with humans. Macaques are highly susceptible to Mycobacterium tuberculosis infection and manifest the complete spectrum of clinical and pathological manifestations of TB as seen in humans. Therefore, the macaque models have been used extensively for investigating the pathogenesis of M. tuberculosis infection and for preclinical testing of drugs and vaccines against TB. This review focuses on published major studies that exemplify how the rhesus and cynomolgus macaques have enhanced and may continue to advance global efforts in TB research.

TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines.

Abstract: Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guerin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients. We evaluated 76 individuals, with tuberculosis active, treated and subjects with positive PPD. Granuloma formation was induced in the presence or absence of Infliximab for up to 10 days. The use of Infliximab in cultures significantly blocked TNF-α production (p <0.05), and led to significant changes in granuloma structure, in vitro, only in the treated TB group. On the other hand, there was a significant reduction in the levels of IFN-γ, IL-12p40, IL-10 and IL-17 after TNF-α blockade in the three experimental groups (p <0.05). Taken together, our results demonstrate that TNF-α blockade by Infliximab directly influenced the structure of granuloma only in the treated TB group, but negatively modulated the production of Th1, Th17 and regulatory T cytokines in the three groups analyzed.