Initiation Of Anti-tuberculosis Treatment Research Articles

Effectiveness of food supplement on treatment outcomes and quality of life in pulmonary tuberculosis: Phased implementation approach.

By encouraging treatment adherence and lowering mortality, dietary supplements can serve as adjuvant therapy for the success of medical interventions. We determined the effect of locally accessible food supplements on treatment outcomes, and health-related quality of life in patients with pulmonary tuberculosis initiating anti-tuberculosis treatment (ATT) in Odisha, India. Between September 2017 and December 2018, implementation research in patients with newly diagnosed sputum smear-positive pulmonary tuberculosis initiating ATT in five districts of the tribal belt of Odisha, offered food supplements along with ATT in a phased manner. Clinical symptoms, anthropometry, sputum for M. tuberculosis (M. tb), health-related quality of life and return to normal function were assessed periodically, and favourable treatment outcome (cure or treatment completed) was measured at the end of treatment. The effect of the food supplement on unfavorable outcomes (treatment failure, death, or lost-to-follow-up) was modelled using mixed-effects Poisson regression to determine the risk factors. Among the 761 participants enrolled, 614 participants received the food supplement and 147 did not receive the food supplement. Among the 614 participants in the supplement group, 537 (87%) had a favorable outcome and among the 147 participants in the no-supplement group, 113 (77%) had a favorable outcome (p = 0.0017). Higher age (>55 years) [aRR = 2.1(95% CI: 1.1-3.8)], male gender [aRR = 1.7(95% CI: 1.2-2.9)], and smear grading ≥2+ [aRR = 1.5 (95% CI: 1.1-2.2)] were associated with unfavorable treatment outcomes. Nutritional status, quality of life and lung health showed significant improvement from baseline in the supplement group. Improvement in the nutritional status of the patient can be considered a predictor of treatment success rates. Early food supplementation has a positive impact on the nutritional status.

Laryngeal tuberculosis, the great deceiver: A series of 10 cases

BackgroundLaryngeal involvement is rare in tuberculosis, representing around 1% of all cases of this infection worldwide. Given the larynx’ location in the airway, this form of tuberculosis is of particular importance because it is highly contagious. With our hospital being in a high tuberculosis burden area, we propose to characterize the clinical presentation, evolution, and laryngoscopy findings of a series of laryngeal tuberculosis cases in order to reduce misdiagnosis. MethodsEpidemiological and clinical data from 10 patients diagnosed with laryngeal tuberculosis in the Otorhinolaryngology department of (Blinded for manuscript) between January 2011 and December 2021 were retrieved and analyzed. ResultsThere were eight males and two females. Seven patients had a history of smoking and alcohol abuse and four had silicosis. Hoarseness was the most reported symptom (n = 9). The most frequent site of involvement were the true vocal cords (n = 6). All patients but one had concomitant active pulmonary tuberculosis. Patients had full resolution of laryngeal symptoms between 4 and 16 weeks after initiating antituberculosis treatment. ConclusionLaryngeal tuberculosis is indeed a great deceiver. On one hand it can look like a simple polypoid lesion or simulate laryngopharyngeal reflux; but on the other hand its risk factors, symptoms and appearance simulate laryngeal carcinoma like no other. Since most patients present with concomitant pulmonary tuberculosis, all suspect laryngeal lesions should perform a chest radiograph prior to rigid laryngoscopy. Antituberculosis treatment is effective in both alleviating symptoms and reducing the risk of transmission.

Cost-effectiveness analysis of interventions to improve diagnosis and preventive therapy for paediatric tuberculosis in 9 sub-Saharan African countries: A modelling study.

Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention. We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded. In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context. This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).

Serum biomarkers for monitoring response to tuberculosis treatment: an assessment of the effect of different covariates among slow and fast treatment responders

Introduction The long duration of tuberculosis treatment, as well as the 2-year post-treatment follow-up period often required for predicting relapse, present a hindrance to drug development and treatment monitoring efforts. Therefore, there is need for treatment response biomarkers to inform treatment time shortening, clinical decision-making, and inform clinical trials. Objectives To assess the abilities of serum host biomarkers to predict treatment response among active PTB patients. Methods Active pulmonary TB patients (n = 53) as confirmed by sputum MGIT culture were enrolled at a TB treatment centre in Kampala, Uganda. We evaluated concentrations of 27 serum host biomarkers at baseline, month 2, and month 6 following the initiation of anti-tuberculosis treatment using the luminex platform for their ability to predict sputum culture status at month-2 post treatment initiation. Results There were significant differences in concentrations of IL1ra, IL1β, IL6, IP10, MCP-1, and IFNγ during treatment. A bio-signature comprising TTP, TNFα, PDGF-BB, IL9, and GCSF best predicted month 2 culture conversion with sensitivity and specificity of 82% (95% CI; 66 -92% and 57 -96% respectively). Slow anti-TB treatment responders had higher pro-inflammatory marker levels during treatment. The strongest correlation was observed between VEGF and IL12p70 (0.94), IL17A and basic FGF (0.92), basic FGF, and IL2 (0.88), and IL10 with IL17A (0.87). Conclusion We identified host biomarkers that predicted early response to PTB treatment, which may be valuable in future clinical trials and treatment monitoring. Similarly, strong correlations between biomarkers provide options for biomarkers substitutions during the development of treatment response monitoring tools or point of care tests.

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/μL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

Combination with reserved prognosis: TB- rheumatoid arthritis

Abstract As shown in a Spanish study, patients with rheumatoid arthritis (PAR) have a 4-fold increased risk of developing TB (tuberculosis) compared to the general population. Abruptly stopping anti-TNF (tumor necrosis factor α) agents after the development of TB could cause a paradoxical response leading to severe complications and death. We present the case of a 54 years old female patient with seropositive PAR since 2012 in treatment with biological therapy, which was diagnosed 10 years after the start of immunosuppressive treatment with miliary TB. She has had an unfavorable prognosis, dying after one month from the initiation of antituberculosis treatment due to septic shock. Therefore, it is very important to evaluate the bacillary status before initiating any immunosuppressive treatment.

A CROSS-SECTIONAL STUDY TO FIND THE PREVALENCE OF IMPAIRED GLUCOSE TOLERANCE IN PULMONARY TUBERCULOSIS PATIENTS

Introduction: Higher prevalence of pulmonary tuberculosis in a diabetic patient is a well-known fact. The inverse relationship i.e. higher prevalence of impaired glucose tolerance in a tuberculous population is also being increasingly realized now and it becomes more relevant due to increased prevalence of DM in general population. Aim/ Objective: To nd the prevalence of abnormal glucose tolerance in pulmonary tuberculosis patients and to correlate the glycaemic parameters with the grades of sputum AFB positivity. Materials &amp; Methods: A hospital based prospective observational comparative study was conducted at a tertiary care hospital. A total of 100 consecutive eligible patients of tuberculosis, were included after taking informed parental consent. Data was analyzed using statistical software SPSS ver. 21. Results: Mean age of the study cases was 42.59 years with 78% males to 22% females. On Oral glucose tolerance test, 56% had normal results while 44% had deranged results. Out of the total 44 cases with deranged results, 13% had IGT and 31% had diabetes. A signicant association was observed between deranged OGTT values and higher sputum grades (p&lt;0.05). Glycemic control as measured by glycated haemoglobin was signicantly associated with grade of sputum positivity. HbA1c levels were 5.98% in cases with “scanty” grade while it was 6.18%, 6.53% and 6.99% in cases with grade +1, +2 and +3 respectively (p&lt;0.05). Conclusion: We observed high prevalence of impaired glucose tolerance and diabetes in tuberculosis patients. Impaired results were signicantly associated with higher degree of sputum positivity. We thus recommend diabetes screening in all TB patients by either HbA1c or OGTT and glucose levels should be measured at least every 2 months after the initiation of anti-tuberculosis treatment.

Tuberculosis Treatment Response Monitoring by the Phenotypic Characterization of MTB-Specific CD4+ T-Cells in Relation to HIV Infection Status.

HIV infection causes systemic immune activation, impacts TB disease progression and hence may influence the diagnostic usability of Mycobacterium tuberculosis-specific T cell profiling. We investigated changes of activation and maturation markers on MTB-specific CD4+ T-cells after anti-tuberculosis treatment initiation in relation to HIV status and the severity of lung impairment. Thawed peripheral blood mononuclear cells from TB patients with (n = 27) and without HIV (n = 17) were analyzed using an intracellular IFN-γ assay and flow cytometry 2 and 6 months post-TB treatment initiation. H37Rv antigen was superior to the profile MTB-specific CD4+ T-cells phenotype when compared to PPD and ESAT6/CFP10. Regardless of HIV status and the severity of lung impairment, activation markers (CD38, HLA-DR and Ki67) on MTB-specific CD4+ T-cells declined after TB treatment initiation (p < 0.01), but the expression of the maturation marker CD27 did not change over the course of TB treatment. The MTB-specific T cell phenotype before, during and after treatment completion was similar between people living with and without HIV, as well as between subjects with severe and mild lung impairment. These data suggest that the assessment of activation and maturation markers on MTB-specific CD4+ T-cells can be useful for TB treatment monitoring, regardless of HIV status and the severity of lung disease.

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment.

SummaryBackgroundGlobally, the tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success is lower among people with diabetes mellitus (DM). Predicting treatment outcome early after diagnosis, especially in TB-DM patients, would allow early treatment adaptation for individuals and may improve global TB control.MethodsSamples were collected in a longitudinal cohort study of adult TB patients from South Africa (n = 94) and Indonesia (n = 81), who had concomitant DM (n = 59), intermediate hyperglycaemia (n = 79) or normal glycaemia/no DM (n = 37). Treatment outcome was monitored, and patients were categorized as having a good (cured) or poor (failed, recurrence, died) outcome during treatment and 12 months follow-up. Whole blood transcriptional profiles before, during and at the end of TB treatment were characterized using unbiased RNA-Seq and targeted gene dcRT-MLPA.FindingsWe report differences in whole blood transcriptome profiles, which were observed before initiation of treatment and throughout treatment, between patients with a good versus poor TB treatment outcome. An eight-gene and a 22-gene blood transcriptional signature distinguished patients with a good TB treatment outcome from patients with a poor TB treatment outcome at diagnosis (AUC = 0·815) or two weeks (AUC = 0·834) after initiation of TB treatment, respectively. High accuracy was obtained by cross-validating this signature in an external cohort (AUC = 0·749).InterpretationThese findings suggest that transcriptional profiles can be used as a prognostic biomarker for treatment failure and success, even in patients with concomitant DM.FundingThe research leading to these results, as part of the TANDEM Consortium, received funding from the European Community's Seventh Framework Programme (FP7/2007-2013 Grant Agreement No. 305279) and the Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038). The research leading to the results presented in the Indian validation cohort was supported by Research Council of Norway Global Health and Vaccination Research (GLOBVAC) projects: RCN 179342, 192534, and 248042, the University of Bergen (Norway).

Performance of loop-mediated isothermal amplification assay for diagnosis of extrapulmonary tuberculosis and antituberculosis treatment initiation.

Extra-pulmonary TB(EPTB) accounts for 15-20% of total TB cases in India. Many cases remain undiagnosed due to poor sensitivity/long turn-around-time of conventional diagnostic tests. Molecular tests offer rapidity, improved sensitivity and exquisite specificity, but are expensive, require skilled manpower and enhanced laboratory infrastructure. Loop-mediated isothermal amplification (LAMP) assay is a unique, temperature-independent DNA amplification test facilitated by visual optic-readout. WHO has recommended use of LAMP for pulmonary TB diagnosis in 2016. For END-TB strategy to succeed, its necessary to capture all forms of TB. The aim of the study was to determine the sensitivity and specificity of LAMP assay against culture, Xpert MTB/RIF assay and Composite Reference Standard(CRS) for diagnosis of EPTB. In a cross-sectional study hundred consecutive EPTB specimens were processed for microscopy, culture, Xpert and LAMP assay. Standard formulae of sensitivity and specificity and McNemar chi square test of significance was applied. Hundred specimens included in the study were fluids(65), pus(19) and tissue(16). TB was detected in 38 specimens by any of the four methods. Positivity of microscopy-5%, culture-28%, Xpert-25% and LAMP-32%. Sensitivity and specificity of LAMP against culture was 85.71% and 88.89%; against Xpert was 88% and 86.67%; against CRS was 80% and 88.6% respectively. LAMP detected TB in 32 patients of which 28 were put on anti-TB treatment (ATT). Of the 62 patients with negative results in all the tests, 22 were put on ATT. LAMP has good sensitivity for EPTB diagnosis. Further studies are required to establish utility of LAMP as EPTB diagnostic tool.

Diagnostic performance of DNA microarray for detecting rifampicin and isoniazid resistance in Mycobacterium tuberculosis

BackgroundWhile rifampicin (RFP) and isoniazid (INH) are the most commonly used first-line antituberculosis drugs, multidrug resistance in Mycobacterium tuberculosis poses a threat to the success of tuberculosis (TB) control programs. Clinical practice guidelines and expert consensuses recommend drug susceptibility testing (DST) before the initiation of antituberculosis treatment. However, traditional DST is time-consuming and has high requirements for laboratory conditions. The recently developed molecular diagnostic techniques, such as DNA microarray, offer new options. We thus investigated the diagnostic value of DNA microarray in detecting RFP + INH-resistant TB, with an attempt to identify simple, efficient, and accurate drug-resistant TB testing methods.MethodsThe clinical features and DST results of patients diagnosed with pulmonary tuberculosis by Bactec MGIT 960 liquid culture system (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) who received DNA microarray analysis in our center from July 2019 to July 2020 were retrospectively analyzed. Level of agreement between liquid culture and DNA microarray technology was assessed by using the Cohen kappa coefficient. With the results of liquid culture as the gold standard, the sensitivity and specificity of the DNA microarray were calculated, and the receiver operating characteristic (ROC) curves were used to assess the diagnostic values of the DNA microarray in detecting RFP + INH-resistant TB.ResultsA total of 825 patients were enrolled. The sensitivity and specificity of DNA microarray were 0.84 and 0.94, respectively, in the detection of RFP resistance, with an area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87–0.91)] and a Cohen kappa coefficient of 0.78 (95% CI: 0.72–0.83). For INH resistance, the sensitivity and specificity of the DNA microarray were 0.73 and 0.97, respectively, with an AUC of 0.85 (95% CI: 0.82–0.87) and a Cohen kappa coefficient of 0.75 (95% CI: 0.70–0.80).ConclusionsThe DNA microarray had high specificity and sensitivity in detecting RFP + INH-resistant TB. As a rapid, accurate, and practical technique, it can be routinely performed in clinical laboratories.

Measuring health-care delays among privately insured patients with tuberculosis in the USA: an observational cohort study

A high index of suspicion is needed to initiate appropriate testing for tuberculosis due to its protean symptoms, yet health-care providers in low-incidence settings are becoming less familiar with the disease as rates decline. We aimed to estimate delays in tuberculosis diagnosis and treatment at the US national level between 2008 and 2016. In this retrospective observational cohort study, we repurposed private insurance claims data provided by Aetna (Connecticut, USA), to measure health-care delays in tuberculosis diagnosis in the USA in 2008-16. Active tuberculosis was determined by diagnosis codes and the filling of anti-tuberculosis treatment prescriptions. Health-care delays were defined as the duration between the first health-care visit for a tuberculosis symptom and the initiation of anti-tuberculosis treatment. We assessed if delays varied over time, and by patient and system variables, using multivariable regression. We estimated household tuberculosis transmission and respiratory complications after treatment initiation. We confirmed 738 active tuberculosis cases (incidence 1·45 per 100 000 person-years) with a median health-care delay of 24 days (IQR 10-45). Multivariable regression analysis showed that longer delays were associated with older age (8·4% per 10 year increase [95% CI 4·0 to 13·1]; p<0·0086) and non-HIV immunosuppression (19·2% [15·1 to 60·0]; p=0·0432). Presenting with three or more symptoms was associated with a shorter delay (-22·5% [-39·1 to -2·0]; p=0·0415), relative to presenting with one symptom, as did use of chest imaging (-24·9% [-37·9 to -8·9]; p<0·0098), tuberculosis nucleic acid amplification tests (-19·2% [-32·7 to -3·1]; p=0·0241), and care by a tuberculosis specialist provider (-17·2% [-33·1 to -22·3]; p<0·0087). Longer delays were associated with an increased rate of respiratory complications even after controlling for patient characteristics, and an increased rate of secondary tuberculosis among dependents. In the USA, the median health-care delay for privately insured patients with tuberculosis exceeds WHO-recommended levels of 21 days (3 weeks). The results suggest the need for health-care provider education on best practices in tuberculosis diagnosis, including the use of molecular tests and the maintenance of a high index of suspicion for the disease. US National Institutes of Health.

Clinically atypical cutaneous mycobacteriosis: A therapeutic challenge.

Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, causes tuberculosis in humans and animals, but the incidence in humans is very low worldwide. Direct contact with animals and with unpasteurized dairy products is the most frequent source of contagion. Cutaneous tuberculosis supposes a diagnostic challenge due to its variety of clinical manifestations and the difficulty in demonstrating resistant acid-alcohol bacilli in histological samples. In cases of high suspicion, the initiation of antituberculosis treatment should be considered empirically. Combined therapeutic regimens are necessary to prevent long-term resistance and complications, although the duration of treatment has not been fully established.

Adherence to Anti-Tuberculosis Treatment Among Pediatric Patients at Nekemte Specialized Hospital, Western Ethiopia.

BackgroundNon-adherence to tuberculosis treatment is the most challenging and hindering factor for successful tuberculosis therapy. The long duration of tuberculosis treatment and the undesirable effects of anti-tuberculosis drugs result in non-adherence to treatment among pediatric patients. Hence, this study was aimed to evaluate pediatrics adherence status among tuberculosis pediatric patients on anti-tuberculosis treatment at Nekemte Specialized Hospital.MethodsA health facility-based cross-sectional study design was used to recruit pediatric TB patients who were receiving their treatment between February 15 and March 15, 2019. Adherence to tuberculosis therapy was evaluated using data obtained from face-to-face interviews of their respective caregivers. The collected data were entered into EPI-manager 4.0.2 software and analyzed using SPSS version 24. Logistic regression was used to analyze the variables and variables with p-value <0.05 had a statistically significant association with the adherence to anti TB treatment.ResultsAmong 202 participants involved in the study, 120 (59.4%) of them were males and 119 (58.9%) were in the age category of 11–15 years. A total of 166 (82.2%) of the patients had extra-pulmonary tuberculosis and 174 (86.1%) of them were in the intensive phase. Of the pediatric tuberculosis patients, 48 (73.3%) of them have adhered to the treatment regimen. Female gender [AOR: 3.3, 95% CI: 1.52–7.2], younger age (0–5 years) [AOR: 5.96 95% CI: 1.81–19.6], living in urban area [AOR: 3.73, 95% CI: 1.67–8.36], and patients who did not experience side effect [AOR: 2.87, 95% CI: 1.41–5.81] were predictors of good adherence to tuberculosis treatment up on multivariable logistic regression analysis.ConclusionThe level of adherence observed in our study area was low. Age, sex, residence, and side effect experience showed an association with tuberculosis treatment adherence. Therefore, health care providers should educate all patients with tuberculosis before the initiation of anti-tuberculosis treatment.

Immune reconstitution inflammatory syndrome in non human immunodeficiency viruses children on anti tubercular treatment

The term IRIS is almost solely used in human immunodeficiency virus seropositive patients who initiated anti-retroviral therapy (ART), the term paradoxical reaction is generally used to describe a clinical worsening of tuberculosis disease after the initiation of antituberculosis treatment. Distinguishing this paradoxical reaction (PR) from disease progression or treatment failure is an important issue in CNS tuberculosis management. Thus, one must keep a watch for neurological deterioration in a child with Central nervous system tuberculosis (CNS TB). We are presenting a case of a non-Human immunodeficiency virus (HIV) child who developed TB-IRIS while on anti-tubercular drugs, who subsequently responded to steroids along with continuation of antitubercular treatment (ATT).

CONCORDÂNCIA INTEROBSERVADORES DA DETECÇÃO DO FATOR CORDA PARA A IDENTIFICAÇÃO PRESUNTIVA DO MYCOBACTERIUM TUBERCULOSIS

Detection of cord factor may favor the definitive diagnosis and initiation of antituberculosistreatment. The aim of this study was to evaluate the interobserver concordance of mycobacterial smears stained with Ziehl-Neelsen technique for the presumptive identification of the Mycobacterium tuberculosis (M. tuberculosis).Three observers, healthcare students, conducted a blind reading of 30 slides stained with Ziehl-Neelsen and their results were compared to the results of an experient reader. Kappa coefficient with 95% interval was used to evaluate the concordance betweenthe readings. No excellent interobserver concordance(κ&gt;0.75) was found. The interpretation and use of the cord factor for the presumptive identification of the M. tuberculosisis a technique that requires training for the interpretation of the variables of the smear stained with Ziehl-Neelsen technique and theoretical knowledge of the observer to deliver a correct result.

Initiation of anti-tuberculosis treatment in children following gastric aspirate testing, Botswana, 2008-2012.

Diagnosing pediatric tuberculosis (TB) is difficult; to improve diagnosis, gastric aspiration (GA) was performed in 121 Botswana health facilities. To describe treatment initiation and outcomes in children with a positive GA result and those treated empirically. Children with smear or culture-positive GA or those clinically diagnosed were referred for anti-tuberculosis treatment. Treatment initiation and outcomes were assessed from February 2008 to December 2012 using name-based matching algorithms of the GA database; treatment initiation was captured in the electronic TB registry. Analyses included descriptive statistics and regression models. GA was conducted in 1268 children. Among these, 121 (9.5%) were GA-positive; and treatment was initiated in 90 (74.3%). An additional 137 (11.9%) were treated empirically. More than a third (36.4%) had known human immunodeficiency virus status (positive or negative); this was significantly associated with TB treatment initiation (adjusted odds ratio [aOR] 1.8, 95%CI 1.3-2.5); P < 0.05). Among the 90 children with a positive GA result, nearly all either completed treatment (78.9%) or were on treatment (20.0%) at the time of data collection. We could not find documentation of treatment for more than a quarter of the children with laboratory-confirmed TB, an important gap that calls for further examination. The failure to initiate prompt treatment requires investigation and urgent action.

Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy.

Background: The analysis of phenotypic characteristics on Mycobacterium tuberculosis (MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied phenotypic changes on MTB-specific CD4 T cells upon anti-tuberculosis treatment initiation in relation to the treatment response as determined by sputum culture.Methods: Peripheral blood mononuclear cells from subjects with latent MTB infection (n = 16) and aTB (n = 39) at baseline, weeks 9, 12, and 26 (end of treatment) were analyzed after intracellular interferon gamma staining and overnight stimulation with tuberculin. Liquid sputum cultures were performed weekly until week 12 and during 4 visits until week 26.Results: T cell activation marker expression on MTB-specific CD4 T cells differed significantly between subjects with aTB and latent MTB infection with no overlap for the frequencies of CD38pos and Ki67pos cells (both p < 0.0001). At 9 weeks after anti-TB treatment initiation the frequencies of activation marker (CD38, HLA-DR, Ki67) positive MTB-specific, but not total CD4 T cells, were significantly reduced (p < 0.0001). Treatment induced phenotypic changes from baseline until week 9 and until week 12 differed substantially between individual aTB patients and correlated with an individual's time to stable sputum culture conversion for expression of CD38 and HLA-DR (both p < 0.05). In contrast, the frequencies of maturation marker CD27 positive MTB-specific CD4 T cells remained largely unchanged until week 26 and significantly differed between subjects with treated TB disease and latent MTB infection (p = 0.0003).Discussion: Phenotypic changes of MTB-specific T cells are potential surrogate markers for tuberculosis treatment efficacy and can help to discriminate between aTB (profile: CD38pos, CD27low), treated TB (CD38neg, CD27low), and latent MTB infection (CD38neg, CD27high).

Outcomes across the tuberculosis care continuum among adolescents in Haiti.

Setting: GHESKIO (Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes) clinic, Port-au-Prince, Haiti. Objective: To evaluate tuberculosis (TB) care continuum outcomes among adolescents. Design: Among a retrospective cohort of 10-24 year olds diagnosed with active TB, we report completion of the following steps of the TB care continuum stratified by human immunodeficiency virus (HIV) status: diagnosis of microbiologically confirmed TB, initiation of anti-tuberculosis treatment, retention in care at 2 months on anti-tuberculosis treatment, and TB treatment success. Factors associated with attrition at each step were identified using multivariable regression. Results: A total of 1005 adolescents were diagnosed with active TB; 74 (7%) were HIV-positive at the time of TB diagnosis. HIV-positive patients had poorer outcomes than non-HIV-infected patients: 73% vs. 85% initiated anti-tuberculosis treatment (P < 0.01), 46% vs. 74% were retained in care at 2 months (P < 0.01), and 41% vs. 68% achieved TB treatment success (P < 0.01). Among those who initiated treatment, same-day initiation resulted in less treatment failure. Attrition before treatment initiation was associated with female sex and HIV coinfection. Attrition after treatment initiation was associated with age ⩾16 years and HIV coinfection. Conclusion: Outcomes across the TB care continuum are suboptimal among adolescents, with only two thirds of patients achieving treatment success. Interventions tailored to adolescents are needed to improve retention in care, particularly for those who are co-infected with HIV.

Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the pharmacokinetics of isoniazid and acetyl-isoniazid.

To describe the pharmacokinetics of isoniazid and acetyl-isoniazid in TB/HIV-coinfected patients, and assess the effects of efavirenz co-administration and a 50% increase in the dose of rifampicin on the pharmacokinetic parameters of isoniazid and acetyl-isoniazid. TB/HIV-coinfected patients participating in the three-treatment-arm RAFA randomized controlled trial conducted in West Africa were recruited into the pharmacokinetics sub-study. Five serial blood samples were collected on a single visit between 4 and 8 weeks after initiation of antituberculosis treatment. Concentration-time data for isoniazid and acetyl-isoniazid were analysed using non-linear mixed-effects models. Isoniazid concentrations from 150 patients were available for analysis, and 79 of these (53%) also had concentrations of acetyl-isoniazid. Isoniazid pharmacokinetics was best described with a two-compartment disposition model with lagged first-order absorption and elimination using a semi-mechanistic model describing hepatic extraction. The model identified two elimination pathways, separating formation of acetyl-isoniazid from other routes of metabolism. The predicted AUC0-24 is reduced by 29% in patients who are fast acetylators of isoniazid and receiving efavirenz-based ART (6.73 versus 4.68 mg·h/L). In slow acetylators, efavirenz-based ART had no effect on isoniazid exposure (AUC0-24 = 17.5 mg·h/L). Efavirenz-based ART affects the acetylation metabolic pathway amongst rapid acetylators, resulting in reduced exposure to isoniazid. Pharmacokinetics of isoniazid and acetyl-isoniazid were not influenced by the 50% increase in rifampicin dose.