The cursed duet today: Tuberculosis and HIV-coinfection

The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed. Also, special topics on drug interactions, TB-IRIS and TB relapse are also described. Notwithstanding the defeats and meagre investments, diagnosis and management of the two diseases have seen significant and unexpected improvements of late. On the HIV side, expansion of ART coverage, development of new updated guidelines aimed at the universal treatment of those infected, and the increasing availability of newer, more efficacious and less toxic drugs are an essential element to controlling the two epidemics. On the TB side, diagnosis of MDR-TB is becoming easier and faster thanks to the new PCR-based technologies, new anti-TB drugs active against both sensitive and resistant strains (i.e. bedaquiline and delamanid) have been developed and a few more are in the pipeline, new regimens (cheaper, shorter and/or more effective) have been introduced (such as the “Bangladesh regimen”) or are being tested for MDR-TB and drug-sensitive-TB. However, still more resources will be required to implement an integrated approach, install new diagnostic tests, and develop simpler and shorter treatment regimens

The consequences of the effects of the chemotherapeutic drug (vincristine) in organs and the influence on the bioavailability of two radio-biocomplexes used for bone evaluations in balb/c female mice

The development of animal model to evaluate the toxicological action of compounds used as pharmaceutical drugs is desired. The model described in this work is based on the capability of drugs to alter the bioavailability of radiopharmaceuticals (radiobiocomplexes) labeled with technetium-99 m(99mTc). There are evidences that the bioavailability or the pharmacokinetic of radiobiocomplexes can be modified by some factors, as drugs, due to their toxicological action in specific organs. Vincristine is anatural product that has been utilized in oncology. The vincristine effect on the bioavailability of the radiobiocomplexes 99mTc- ethylenediphosphonic acid (99mTc-MDP) and 99mTc-pyrophosphate (99mTc- PYP) in Balb/c female mice was evaluated. The fragments of kidney were processed to light microscopy and transmission electron microscopy. The aim of this work was to study at structural and ultrastructural levels the alterations caused by vincristine in organs. One hour after the last dose ofvincristine, 99mTc-PYP or 99mTc-MDP was injected, the animals were sacrificed and the percentage of radioactivity (%ATI) was determined in the isolated organs. Concerning 99mTc-PYP, the %ATI (i) decreased in spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, lung, liver, pancreas, stomach, heart and brain and (ii) increased in bone and thyroid. Concerning 99mTc-MDP, the %ATI (iii) decreased in spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, liver, pancreas,stomach, heart, brain, bone, ovary and uterus. In conclusion, the toxic effect of vincristine in determined organs could be responsible for the alteration of the uptake of the studied radiobiocomplexes

Outcomes of TB Treatment by HIV Status in National Recording Systems in Brazil, 2003–2008

BACKGROUND: Although the Brazilian national reporting system for tuberculosis cases (SINAN) has enormous potential to generate data for policy makers, formal assessments of treatment outcomes and other aspects of TB morbidity and mortality are not produced with enough depth and rigor. In particular, the effect of HIV status on these outcomes has not been fully explored, partly due to incomplete recording in the national database. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, we assessed TB treatment outcomes, including rates of cure, default, mortality, transfer and multidrug resistant TB (MDR-TB) among a purposively chosen sample of 161,481 new cases reported in SINAN between 2003 and 2008. The study population included all new cases reported in the six States with the highest level of completeness of the HIV status field in the system. These cases were mostly male (67%), white (62%), had pulmonary TB (79%) and a suspect chest X ray (83%). Treatment outcomes were best for those HIV negative cases and worst for those known HIV positive patients (cure rate of 85.7% and 55.7% respectively). In multivariate modeling, the risk of having an unfavorable outcome (all outcomes except cure) was 3.09 times higher for those HIV positive compared with those HIV negative (95% CI 3.02-3.16). The risk of death and default also increased with HIV positivity. The group without a known HIV status showed intermediate outcomes between the groups above, suggesting that this group includes some with HIV infection. CONCLUSIONS: HIV status played an important role in TB treatment outcomes in the study period. The outcomes observed in those with known HIV were poor and need to be improved. Those in the group with unknown HIV status indicate the need for wider HIV testing among new TB cases

The effects of a muscle resistance program on the functional capacity, knee extensor muscle strength and plasma levels of IL-6 and TNF-α in pre-frail elderly women: a randomized crossover clinical trial - a study protocol

<p>Abstract</p> <p>Background</p> <p>With the increase in the elderly population, a growing number of chronic degenerative diseases and a greater dependency on caregivers have been observed. Elderly persons in states of frailty remain more susceptible to significant health complications. There is evidence of an inverse relationship between plasma levels of inflammatory mediators and levels of functionality and muscle strength, suggesting that muscle-strengthening measures can aid in inflammatory conditions. The purpose of this study will be verified the effect of a muscle-strengthening program with load during a ten-week period in pre-frail elderly women with attention to the following outcomes: (1) plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), (2) functional capacity and (3) knee extensor muscle strength.</p> <p>Methods/Design</p> <p>The study design is a randomized crossover clinical trial evaluating 26 elderly women (regardless of their race and/or social condition) who are community residents, older than 65, and classified as pre-frail according to the criteria previously described by Fried et al. (2004). All subjects will be assessed using the Timed up and go and 10-Meter Walk Test functional tests. The plasma levels of IL-6 and TNF-α will be assessed by ELISA (<it>enzyme-linked immunosorbent assay</it>) with high sensitivity kits (Quantikine^®HS, R&D Systems Minneapolis, MN, U.S.). Knee extensor muscle strength will be assessed using the <it>Byodex System 3 Pro</it>^{<it>® </it>}isokinetic dynamometer at angular speeds of 60 and 180°/s. The intervention will consist of strengthening exercises of the lower extremities at 50 to 70% of 1RM (maximal resistance) three times per week for ten weeks. The volunteers will be randomized into two groups: group E, the intervention group, and group C, the control group that did not initiate any new activities during the initial study period (ten weeks). After the initial period, group C will begin the intervention and group E will maintain everyday activities without exercising. At the end of the total study period, all volunteers will be reassessed.</p> <p>Discussion</p> <p>To demonstrate and discuss possible influences of load-bearing exercises on the modification of plasma levels of IL-6 and TNF-α and in the functional performance of pre-frail elderly women.</p> <p>Trial Registration</p> <p>ISRCTN62824599</p

Clinical standards for the assessment, management, and rehabilitation of post-TB lung disease

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR). METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement). RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR. CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD

Diagnosis and follow-up of treatment of latent tuberculosis; the utility of the QuantiFERON-TB Gold In-tube assay in outpatients from a tuberculosis low-endemic country

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma (IFN-γ) Release Assays (IGRA) are more specific than the tuberculosis skin test (TST) in the diagnosis of latent tuberculosis (TB) infection (LTBI). We present the performance of the QuantiFERON^®-TB Gold In-tube (QFT-TB) assay as diagnostic test and during follow-up of preventive TB therapy in outpatients from a TB low-endemic country.</p> <p>Methods</p> <p>481 persons with suspected TB infection were tested with QFT-TB. Thoracic X-ray and sputum samples were performed and a questionnaire concerning risk factors for TB was filled. Three months of isoniazid and rifampicin were given to patients with LTBI and QFT-TB tests were performed after three and 15 months.</p> <p>Results</p> <p>The QFT-TB test was positive in 30.8% (148/481) of the total, in 66.9% (111/166) of persons with origin from a TB endemic country, in 71.4% (20/28) previously treated for TB and in 100% (15/15) of those diagnosed with active TB with no inconclusive results. The QFT-TB test was more frequently positive in those with TST ≥ 15 mm (47.5%) compared to TST 11-14 mm (21.3%) and TST 6-10 mm (10.5%), (p < 0.001). Origin from a TB endemic country (OR 6.82, 95% CI 1.73-26.82), recent stay in a TB endemic country (OR 1.32, 95% CI 1.09-1.59), duration of TB exposure (OR 1.59, 95% CI 1.14-2.22) and previous TB disease (OR 11.60, 95% CI 2.02-66.73) were all independently associated with a positive QFT-TB test. After preventive therapy, 35/40 (87.5%) and 22/26 (84.6%) were still QFT-TB positive after three and 15 months, respectively. IFN-γ responses were comparable at start (mean 6.13 IU/ml ± SD 3.99) and after three months (mean 5.65 IU/ml ± SD 3.66) and 15 months (mean 5.65 IU/ml ± SD 4.14), (p > 0.05).</p> <p>Conclusion</p> <p>Only one third of those with suspected TB infection had a positive QFT-TB test. Recent immigration from TB endemic countries and long duration of exposure are risk factors for a positive QFT-TB test and these groups should be targeted through screening. Since most patients remained QFT-TB positive after therapy, the test should not be used to monitor the effect of preventive therapy. Prospective studies are needed in order to determine the usefulness of IGRA tests during therapy.</p