Showing papers in "The Indian journal of tuberculosis in 2019"
TL;DR: Early recognition by active surveillance and appropriate management of adverse drug reactions to drug resistant tuberculosis patients particularly with SLDs' might improve adherence and treatment success.
Abstract: Background Treatment of drug susceptible tuberculosis (DS-TB) requires regimens containing first line drugs (FLDs’) whereas drug resistant tuberculosis (DR-TB) are treated with regimens comprising combination of both second line drugs (SLDs’) and few FLDs’. Adverse drug reactions (ADRs’) to these anti-tubercular drugs are quite common as they are being used for longer duration. ADRs’ may cause associated morbidity and even mortality if not recognized early. There are major concerns regarding treatment of DR-TB patients particularly with SLDs’ in that they are expensive, have low efficacy and more toxic as compared to FLDs’. There may be a severe impact on adherence and higher risk of default and treatment failure affecting outcome overall if such ADRs’ are not properly managed. Methods A search strategy was adopted involving principal electronic databases (Pubmed, EMBASE, Google and Google scholar) of English language articles from 1990 till now, using various terms in combination. All articles with resulting titles, abstract and full text, when available were read and kept for reference. Results 101 articles including 4 systematic reviews have been identified. The overall prevalence of ADRs’ with FLDs’ and SLDs’ are estimated to vary from 8.0% to 85% and 69% to 96% respectively. Most ADRs’ are observed in the intensive phase as compared to continuation phase. No difference in frequency of ADRs’ was reported with intermittent or daily intake of anti-tubercular drugs. The occurrence of ADRs’ may be influenced by multiple factors and may range from mild gastrointestinal disturbances to serious hepatotoxicity, ototoxicity, nephrotoxicity peripheral neuropathy, cutaneous ADRs’, etc. Most of ADRs’ are minor and can be managed without discontinuation of treatment. Some ADRs’ can be major or severe causing life-threatening experience leading to either modification or discontinuation of regimen and even mortality if not recognized and treated promptly. Conclusion Early recognition by active surveillance and appropriate management of these ADRs’ might improve adherence and treatment success.
41 citations
TL;DR: MDR-TB in the private sector results in "catastrophic health costs" and financial and social support is essential for patients undergoing treatment for MDR- TB.
Abstract: Summary Background Private healthcare is choice of point of care for 70% of Indians. Multidrug resistant tuberculosis (MDR-TB) treatment is costly and involves duration as long as 2 years. Aim To estimate costs to patients undergoing treatment for MDR-TB. Methods A health-economics questionnaire was administered to 50 consecutive patients who successfully completed ambulatory private treatment for MDR-TB. Direct costs included drug costs, investigations, consultation fees, travel costs, hospitalisation and invasive procedures and cost prior to presentation to us. Indirect costs included loss of income. Results Of our cohort of 50 patients, 36 had pulmonary TB while 14 had extra-pulmonary TB (EPTB). 40 had MDR-TB and 10 had XDR-TB. There were 15 males and 35 females. Mean age was 30 years (range 16–61 years). Treatment cost for pulmonary MDR-TB averaged $5723 while it averaged $8401 for pulmonary XDR-TB and $5609 for EPTB. The major expense was due to drug costs (37%) while consultation fees were only 5%. Annual individual income for the cohort ranged from $0 to $63,000 (mean $11,430). On average, the cost of treatment ranged from 2.56% to 180.34% of the annual family income. 34/50 (68%) had total costs greater than 20% of annual family income and 39/50 (78%) had total costs greater than 10% of annual family income. The number of patients with total costs >40% of total family income was 22. Conclusion MDR-TB in the private sector results in “catastrophic health costs”. Financial and social support is essential for patients undergoing treatment for MDR-TB.
26 citations
TL;DR: It is highlighted that even with free care for tuberculosis, 21.3% were exposed to hardship financing, suggesting the need to re-look at the subsidy coverage of tuberculosis treatment in the country.
Abstract: Background In 2017, India accounted for 27 percent of the global burden on tuberculosis, and the highest among the top 30 countries with high TB burden. Despite the expansion of DOTS programme many households in India incur high expenditure towards TB treatment. Most of the studies in India have focused on measuring catastrophic health expenditure on TB. Catastrophic health expenditure and its impoverishment effects are difficult to calculate and may misrepresent economic hardship. Methods This paper uses hardship financing, i.e. when a household sells assets or borrows money on interest to pay for healthcare expenditure, as an indicator of the hardship of the family when it spends on TB treatment using NSSO 71st Round 2014 data. Results Using the NSSO national representative sample, the paper estimated that 26.7% of hospitalized cases and 3.5% percent of patients utilising outpatient care experience hardship financing due to TB in the country. 25.9% of the general population had to sell assets or used borrowings for financing TB hospitalization expenses. Education of head of household, income, type of health facility used, and number of hospitalized days were found to be significant factors influencing hardship financing. Conclusion Our study highlights that even with free care for tuberculosis, 21.3% were exposed to hardship financing, suggesting the need to re-look at the subsidy coverage of tuberculosis treatment in the country. The study also suggests the use of hardship financing as an alternative to catastrophic spending method as a index of effectiveness of tuberculosis control programme in the country.
24 citations
TL;DR: BDQ and DLM given together in a salvage regimen is efficacious with low rate of adverse events and the combination provides hope to DR-TB patients with limited treatment options and should be provided as a life saving option.
Abstract: Background Drug-Resistant Tuberculosis (DR-TB) patients for whom a WHO recommended regimen along with Bedaquiline (BDQ) cannot be prescribed, Delamanid (DLM) was added along with other drugs to provide a “Salvage Regimen”. The experience of the Institute in respect of early efficacy and safety of both drugs given together is presented. Objective To ascertain the early efficacy, safety and tolerability of Bedaquline and Delamanid given together as a part of salvage regimen. Methods BDQ and DLM were used together to make regimens along with other drugs where four effective anti TB drugs could not be prescribed as per WHO recommendations. Patients were followed up for sputum smear and culture conversion and adverse events during the treatment. Results In this cohort study, 53 DR-TB patients (Median age-24) were initiated on regimens containing both BDQ and DLM. Sputum smear conversion was seen in 35% and 94% patients at the end of 1st week and 3rd month respectively. 84% patients had culture conversion at the end of 4th month. 29 adverse events (AE) were reported among 17 patients and there were 11 deaths. QTc prolongation more than 500 MS was seen in only 1 patient. Conclusion BDQ and DLM given together in a salvage regimen is efficacious with low rate of adverse events. The combination provides hope to DR-TB patients with limited treatment options and should be provided as a life saving option.
23 citations
TL;DR: Couning and counseling with leaflet impact in patients' adherence to tuberculosis medication improved patients' adhere compare to control group with p-values of 0.028 and 0.001 respectively.
Abstract: Background One of the goals of counseling in patients with chronic diseases including tuberculosis patients is to improve adherence to taking medication. By patient adherence, therapeutic results are more optimal. Additional counseling alternatives such as leaflets may be needed to make easier for patients to obtain information about their treatment. This study aimed to analyze the effectiveness of counseling with and without leaflets on the adherence on taking tuberculosis (TB) drugs. Methods This study was a quantitative research conducted using a quasi-experiment method with a control group for pre-test and post-test design. Data was taken by consecutive sampling. The number of samples in this study was 75 respondents which divided into three groups: counseling, counseling with leaflets, and control that is a usual care in hospital. The inclusion criteria were patients diagnosed with pulmonary tuberculosis with age 25–55 years, who has been taking TB medicines for at least one month and can communicate well. Data was analyzed using Wilcoxon and Kruskal–Wallis with post hoc Mann–Whitney due to abnormality of the distributed data. Results Before the intervention, of 20 respondents (42.6%) out of 75 respondents were obedient to their TB medicines, whereas after the intervention the number of obedient patients was 33 respondents (70.2%). There was a significant increase in adherence between before and after two weeks of counseling intervention with a p-value of 0.029 before and after two weeks of counseling with leaflets with a p-value of 0.003. Counseling and counseling with leaflets improved patients' adherence compare to control group with p-values of 0.028 and 0.001 respectively. Conclusion Counseling and counseling with leaflet impact in patients' adherence to tuberculosis medication.
22 citations
TL;DR: Prevalence of anemia among TB patients was high especially among women, more than 43% of these patients suffered from moderate and severe anemia and about half of them had chronic disease anemia.
Abstract: Introduction Anemia is one of the most common hematologic problems occurs among patients with tuberculosis (TB). Many studies have been carried out estimating the prevalence of anemia among TB patients in different countries reported various results. This study aims to estimate the combined estimate of the anemia prevalence among these patients using systematic review and meta-analysis. Methods Required primary studies were provided after a comprehensive and systematic search in PubMed, Scopus, Science direct, Web of Science and also Google scholar search engine. These studies were then quality assessed using Newcastle–Ottawa Scale checklist. Random effects model was applied for combining the point prevalence with 95% confidence intervals. Results Of 41 papers entered into the meta-analysis, prevalence (95% confidence interval) of anemia among all TB patients as well as men and women were 61.53% (53.44–69.63), 66.95% (51.75–82.14) and 72.67% (60.79–84.54) respectively. Prevalence (95% confidence intervals) of mild, moderate and severe anemia were 35.67% (27.59–43.46), 31.19% (25.15–37.24) and 11.61% (7.88–15.34) respectively. In addition, prevalence (95% confidence intervals) of chronic disease anemia and iron deficiency anemia were 49.82% (15.58–84.07) and 20.17% (6.68–33.65) respectively. Conclusion Prevalence of anemia among TB patients was high especially among women. More than 43% of these patients suffered from moderate and severe anemia and about half of them had chronic disease anemia.
22 citations
TL;DR: Findings of this study will aid in providing baseline evidence to periodically measure the OOP which is the one of the End TB strategy target and be useful for policy makers to design an intervention to provide financial protection to TB patients.
Abstract: Background Tuberculosis (TB) patients often incur large costs related to illness, as well as for seeking and receiving health care. Despite TB treatment being free under RNCTP, out of pocket expenditure incurred (OOP) by patients for TB diagnosis and treatment impoverishes the households. This expenditure may turn catastrophic (more than 20% of their family income) impacting adherence and leading to poor treatment outcomes. Objective To estimate the proportion of households experiencing catastrophic expenditure due to TB and also to find out the various costs contributing to catastrophic expenditure. Methods In this cohort study, 450 TB patients (including 96 children) registered under Revised National Tuberculosis Control Programme (RNTCP) in Delhi were interviewed at three different time points (in the beginning of treatment, end of intensive phase, end of treatment). Interview schedule was used to collect information on direct medical and non-medical, and indirect costs. The TB-specific indicator of “catastrophic total costs” incorporates both, direct medical and non-medical payments for treatment such as transportation, lodging charges and indirect costs such as wage loss. Results A total of 450 patients were enrolled in this study, out of which 425 were followed up to the end of treatment. It was observed that 7% of TB patients registered under RNTCP in Delhi experienced catastrophic expenditure due to TB. The total mean cost to patients with TB was Rs. 12165 (Rs. 1406 during diagnosis and Rs. 10759 during treatment). The indirect cost was higher compared to direct cost i.e.Rs. 7564 and Rs. 4601 respectively). Conclusion This information will be useful for policy makers to design an intervention to provide financial protection to TB patients. In addition, findings of this study will aid in providing baseline evidence to periodically measure the OOP which is the one of the End TB strategy target.
20 citations
TL;DR: The present study emphasize on the need for early diagnosis and treatment of tuberculosis preferably before pregnancy, regular medical follow up and good perinatal care.
Abstract: Tuberculosis (TB) is a major health problem and a leading cause of illness and death from infectious disease. Tuberculosis in pregnancy has been associated with increased risks of prematurity and small for gestational age (SGA)infants.The present study is aimed to examine obstetrical and perinatal outcomes among women who had extra-pulmonary tuberculosis. Material and methods It was retrospective study involving patient who presented with extra pulmonary tuberculosis over a period of ten years (2008–2017)was reviewed. Diagnosed women were compared with controls in the ratio of six controls for each case. Data included age, parity and complications in the antenatal, intrapartum and postpartum periods. The mean birth weights of infant and the frequency of small for gestation age, neonatal depression and still births were used for perinatal outcome. Results During the period of study 30 pregnant women were booked for extra –pulmonary TB. 22/30(73.3%) were diagnosed having extra pulmonary -TB prior to pregnancy and were taking ATT (anti-tubercular therapy) during the pregnancy, in 8/30(26.6%) it was diagnosed during pregnancy. Age, parity were similar in two groups. There was significantly increased incidence of oligoamnios and preterm rupture of membrane (P = 0.001). Mean gestation age of delivery in TB cases was 36.15 ± 1.8 weeks as compared to37.5 ± 0.5 weeks in low risk patients (P = 0.001). The mean birth weight of the infants of mother with extra pulmonary TB was 2324.26 ± 379.5 grams and 2712.3 ± 635.7 for control group(P = 0.001). Conclusion This study emphasize on the need for early diagnosis and treatment of tuberculosis preferably before pregnancy, regular medical follow up and good perinatal care.
20 citations
TL;DR: The recent understanding of drug efflux in Mycobacterium tuberculosis (MTB) is described, a ubiquitous mechanism responsible for innate and acquired drug resistance in prokaryotic and eukaryotic cells.
Abstract: Tuberculosis (TB) remains an important global public health issue with an approximate prevalence of 10 million people with TB worldwide in 2015. Since antibiotic treatment is one of the foremost tools for TB control, knowledge of Mycobacterium tuberculosis (MTB) drug resistance is an important component for disease control. Although gene mutations in specific loci of the MTB genomes are reported as the primary basis for drug resistance, additional mechanisms conferring resistance to MTB are thought to exist. Efflux is a ubiquitous mechanism responsible for innate and acquired drug resistance in prokaryotic and eukaryotic cells. MTB presents a large number of putative drug efflux pumps compared to its genome size. Bioinformatics-based evidence has shown an association between drug efflux and innate or acquired resistance in MTB. This review describes the recent understanding of drug efflux in MTB.
19 citations
TL;DR: Metformin enhances the effects of anti-TB and insulin therapy in increasing the smear reversion by increasing autophagy in patients with type 2 DM newly TB co-infection patients.
Abstract: Metformin (MET) is a potential combination drug to elevate anti-TB efficacy. However, the clinical effect, especially smear reversion, during metformin applied with anti-tuberculosis and insulin in patients with type 2 DM newly TB co-infection were remain unknown. An observational clinical study was done in DM newly TB co-infection outpatients at Surabaya Paru Hospital. This study evaluated MET therapy, at least 2 months, accompanying with insulin and anti-TB regimens and compared to comparison group. The smear, microtubule-associated Protein1 Light Chain 3B (MAP1LC3B) level, as the presentation of autophagy, Superoxide Dismutase (SOD) level, Interferon (IFN)-γ and Interleukin (IL)-10 levels were evaluated twice. From 42 participants in this study, 22 participants of observation group that received additional MET therapy, 100% had sputum smear reversion after 2-months intensive phase of anti-TB therapy. Whereas 25% of 20 participants of comparison group did not undergo reversion inserts sputum smear. As conclusion, MET has the potential of being an additive combination therapy to enhance the bactericidal effect of anti-TB on DM-TB coinfection patients. Metformin enhances the effects of anti-TB and insulin therapy in increasing the smear reversion by increasing autophagy.
17 citations
TL;DR: Integrated support seems to significantly increase the treatment success rate and improve survival and treatment adherence of DRTB patients, however, early diagnosis and effective pharmacotherapy are crucial for reducing treatment failures.
Abstract: Objective To assess the impact of providing integrated psycho-socio-economic support to drug resistant tuberculosis (DRTB) patients on the treatment outcome under programmatic conditions. Study design Retrospective cohort study. Setting An urban district TB centre in India under the Revised National Tuberculosis Control Programme. Participants A cohort of 123 patients who started DRTB treatment between June 2010 and May 2013. Methods Patients started on treatment for DRTB between June 2010 and May 2013 who were provided with the integrated support package for at least 3 months formed the supported group while the other patients of the cohort formed the non-supported group. The treatment outcomes and sputum culture conversion rates were compared between the two groups. Results The supported group consisted of 60 patients and the non-supported group of 63 patients. The treatment success rate was found to be significantly higher in the supported group (65% vs 46.03%; p = 0.0349). Support duration was significantly associated with lower incidence of death [HR 0.876, 95% CI 0.811–0.947; p = 0.0009] and loss to follow up [OR: 0.752, 95% CI 0.597–0.873; p = 0.0023]. The treatment failure rate was higher in the supported group (16.66% vs 4.76%) with 60% of the failures in the supported group occurring after 24 months of compliant treatment. There was no significant association found between support duration and treatment failure or sputum culture conversion. Conclusion Integrated support seems to significantly increase the treatment success rate and improve survival and treatment adherence of DRTB patients. However, early diagnosis and effective pharmacotherapy are crucial for reducing treatment failures.
TL;DR: India has a long road ahead to reach the "End TB by 2025" goal but it needs a refocusing of TB control strategies towards nutrition at all levels and strong public health actions for effective implementation.
Abstract: Many western societies have eliminated tuberculosis years before the advent of potent anti-tuberculous drugs, as a result of the improved standards of living and good nutrition. But even with the availability of powerful anti-tuberculous drugs, India still has a long road ahead to reach the "End TB by 2025" goal. One of the major reason is that tuberculosis control program in India till now have focused primarily on case detection and medical treatment of active tuberculosis. Drug treatment alone does not completely prevent the occurrence of new infections in the community and also contributes to development of drug resistant strains if used improperly or incompletely. Although the treatment of active cases can reduce the period of transmission of disease, a significant amount of transmission to contacts occurs even before they have been diagnosed and treated. Additionally, this approach cannot prevent re-activation to active TB in the vast pool of persons with latent TB infection. Tuberculosis occurs in those with suppressed cell mediated immunity mainly due to poor nutritional status. Improving the nutritional status of the society by several social interventions hand-in-hand with utilizing the available anti-tuberculous drugs is possibly the only effective strategy. Promising programmatic guidance for nutritional support in TB patients have been formulated by the Central TB division of India but it needs a refocusing of TB control strategies towards nutrition at all levels and strong public health actions for effective implementation.
TL;DR: There is a need to develop unified guidelines for monitoring ototoxicity, improving physician awareness and educating patients/caregivers for reporting symptoms of hearing loss in Indian patients with multidrug resistant tuberculosis treated with SLIs.
Abstract: Second-line injectables (SLIs) form an essential class of agents in the treatment of drug resistant (DR) tuberculosis (TB). However, their use is sometimes limited due to serious adverse events like ototoxicity and hearing loss, leading to permanent hearing loss if SLIs are continued. Globally as well as in India a wide variation in incidence of ototoxicity/hearing loss has been reported in patients with DR-TB. In this systematic analysis, we attempt to ascertain the ototoxicity of SLIs in Indian patients with multidrug resistant tuberculosis (MDR-TB) wherein ototoxicity onset was assessed using audiometry performed at both pre- and post-SLI treatment initiation. Twenty two studies were identified based on the inclusion criteria. Ototoxicity was observed in 10.12% [349/3447] patients within 3.8 ± 2.6 months of treatment initiation when the ototoxicity was assessed either with or without audiometry assessment. Only five studies reported ototoxicity assessment with PTA at both pre- and post-SLI initiation and ototoxicity was observed in 27.01% (121/448) patients in these five studies. Sensorineural loss was observed in three studies (high frequency loss: capreomycin, 25.0% [1/4 patients]; amikacin, 19.7% [12/61]; kanamycin, 13.3% [22/166]; streptomycin, 11.8% [2/17]; flat loss: amikacin, 8.2% [5/61]; streptomycin, 5.9% [1/17]; kanamycin 4.8% [8/166]). Most of the patients experiencing ototoxicity were managed by discontinuing (49.6% [120/242]) or replacing SLI treatment (40.8% [49/120]). The study identified high prevalence of ototoxicity in Indian patients with DR-TB treated with SLI when ototoxicity was monitored regularly using PTA (27.01%), warranting a need to develop unified guidelines for monitoring ototoxicity, improving physician awareness and educating patients/caregivers for reporting symptoms of hearing loss.
TL;DR: This is the first case-control study that finds an association between CC genotype of FokI SNP in the VDR gene with pulmonary tuberculosis in Mexican patients, and no statistically significant associations were observed in genotype and haplotype distribution.
Abstract: Background and aims The impact of host genetic variation in susceptibility of tuberculosis is well documented. The vitamin D receptor gene (VDR) is a transacting transcription factor which mediates innate immune response by enhancing the expression of several antimicrobial peptides, including cathelicidin. An association between VDR polymorphisms with tuberculosis (TB) has been investigated in different ethnic groups; however there are contradictions and inconsistencies in the results. The aim of this study was to evaluate the association between polymorphisms of functional VDR with the susceptibility to pulmonary tuberculosis in a Mexican population. Methods A case–control study was performed in, 257 patients with pulmonary tuberculosis and 457 healthy controls recruited from: family medicine clinics of the Mexican Social Security Institute. The VDR gene polymorphisms Fok I (rs 2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were genotyped by TaqMan assays. Statistical analysis was performed using: Epi Info V-7 and SNP Stats software. Results No statistically significant associations were observed in genotype and haplotype distribution between BsmI, ApaI and TaqI polymorphisms and disease susceptibility. The CC genotype for the VDR gene FokI was significantly more frequent in patients than in controls (29.6% versus 17.5%, OR = 1.97; 95% CI = 1.37–2.8, PC = 0.0004). Moreover, TT genotype was decreased in patients as compared to the control group (24.1% versus 34.8%, OR = 0.59; 95% CI = 0.42–0.84, PC = 0.004). Conclusion To our best knowledge, this is the first case-control study that finds an association between CC genotype of FokI SNP in the VDR gene with pulmonary tuberculosis in Mexican patients. However more validation studies should be performed to prove our conclusions.
TL;DR: It is very difficult to differentiate between tubercular and non-tubercular pathology of spine on the basis of most of the clinical and MRI features, and histopathological confirmation is must for further management and percutaneous transpedicular needle biopsy is the best option considering the simplicity and minimally invasive nature of the procedure.
Abstract: Introduction Tuberculosis (TB) has long been an important cause of destructive lesions of spine in India. However the scenario is fast changing with atypical presentations and increasing reports of non-tubercular conditions. This poses a great diagnostic dilemma. Aim The present study is aimed at evaluating the diagnostic efficacy of percutaneous transpedicular needle biopsy and the correlation of the histology with clinico-radiological features. Methods Forty-one patients diagnosed of TB spine by magnetic resonance imaging (MRI) were revaluated of their clinical presentations, radiological and MRI features and underwent transpedicular needle biopsy under fluoroscopic guidance. Quality of the sample and radiological/MRI features between the tubercular and non-tubercular lesions were studied. Results A good sample obtained in 92.7% patients. Of these 28 patients had TB, 3 non-specific inflammatory lesion and 7 with other non-tubercular conditions (3 pyogenic, 3 metastasis, 1 multiple myeloma). Statistically there is no significant difference among the TB and non-TB groups in terms of vertebral involvement and MRI features. However risk of presentation with cord compression, cord changes and neurodeficit are higher with TB spine. Conclusion It is very difficult to differentiate between tubercular and non-tubercular pathology of spine on the basis of most of the clinical and MRI features. It is more difficult in early cases without any neurodeficit. Thus histopathological confirmation is must for further management and percutaneous needle biopsy is the best option considering the simplicity and minimally invasive nature of the procedure.
TL;DR: A research agenda is outlined for generating evidence towards the evolution of critical evidence-based policy for LTBI management under Indian health settings and for accelerating and prioritize capacity building in latent TB research.
Abstract: The elimination of Tuberculosis (TB) in settings with a high dual burden of active and latent TB is one of the most important public health challenges of the 21st century. India has the highest TB burden in the world and nearly 40% of the population being infected with TB. There also exist large often overlapping socially and medically vulnerable populations like the PLHIV, pediatric TB contacts, children with protein-energy malnutrition, homeless people, workers in silica industry and adults with low BMI. A significantly higher risk of progression into active tubercular disease exists in those with compromised immune or nutritional status. It is uncertain if global TB elimination targets can be achieved in the absence of aggressive LTBI treatment strategies for interrupting the chain of transmission of the disease. India hence needs to accelerate and prioritize capacity building in latent TB research. A research agenda is outlined for generating evidence towards the evolution of critical evidence-based policy for LTBI management under Indian health settings.
TL;DR: This review article aims to highlight the recent developments in the anti-tuberculosis agents, those are currently in the clinical development stage.
Abstract: Tuberculosis (TB) being the leading infectious killer in the domain wherein globally, almost 20% of all TB strains are resistant to at least 1 major TB drug and there's a growing incidence of multi-drug resistance tuberculosis (MDR-TB) Looking at the current scenario and challenges the existing strategies fall back in terms of treatment of TB So, to overcome this new, stronger, improved TB drug pipeline and a new standard for the development of novel anti-TB drugs are required in order to make more drug-resistant and efficient drug which also lower the duration period of the treatment of the TB This review article aims to highlight the recent developments in the anti-tuberculosis agents, those are currently in the clinical development stage
TL;DR: Program managers may use sensitivity and specificity estimates for screening tools for PTB and sputum microscopy while evaluating algorithms for active case finding.
Abstract: Setting Community based five pulmonary tuberculosis (PTB) surveys among adults. Objectives Estimate sensitivity and specificity of screening tools for PTB and sputum microscopy. Methods For each survey site, we estimated sensitivity and specificity of different screening criteria and microscopy against culture; pooled estimates were obtained using Random Effects Model. Results Sensitivity of cough alone, screening for any symptom (persistent cough ≥2 weeks, fever or chest pain ≥1 month, hemoptysis), any symptom or history of anti-TB treatment (h/o ATT) were 56.2%, 66% and 71.2% respectively; specificities were 95.3%, 93.8% and 92.7% respectively. X-ray when used alone for primary screening had sensitivity and specificity of 76.6% and 97.3% respectively. When used along with screening for cough, these figures were 94.3% and 93.1%, and 100% and 97.3% when used with any symptom and h/o ATT. When used for secondary screening, sensitivity and specificity of X-ray was 66.8% and 87.8% respectively after primary screening for cough, 65.0% and 89.8% after screening for any symptom, and 67.1% and 86.7% when used after screening for any symptom or h/o ATT. Pooled sensitivity and specificity of smear was 46.2% and 99.3% respectively. Conclusion Program managers may use these estimates while evaluating algorithms for active case finding.
TL;DR: It is concluded that HRQOL is significantly reduced in patients with PTB, and that it improves rapidly and significantly with DOTS-based intensive phase of treatment.
Abstract: Background Pulmonary Tuberculosis (PTB) is a contagious, airborne infection that destroys when M tuberculosis primarily attacks the lungs PTB is curable with an early diagnosis and antibiotic treatment Stigmatization and negative emotions resulting from the illness could result in long term impairment of patients psychological well being which may result in work absenteeism resulting in loss of productivity and reduced monthly income Methods This was a prospective study which was conducted over a period of one and half year A total of 198 patients were recruited for the study Quality Of Life (QOL) was assessed at baseline and at the end of intensive phase For QOL WHO based QOLBREF was used Results In the present study patients scored lowest in the baseline physical (836 ± 160) followed by the psychological domain (1040 ± 172) however at the end of intensive phase both physical (1198 ± 170) and psychological (1275 ± 1) domains improved very much and the difference was statistically significant Conclusion We conclude that HRQOL is significantly reduced in patients with PTB, and that it improves rapidly and significantly with DOTS-based intensive phase of treatment Special focus on reduction of stigmatization should be given in the management of TB to reduce the psychological distress
TL;DR: Xpert MTB/RIF assay uses various combinations of probe to detect MTB along with rifampicin resistance and is a valuable diagnostic tool that can become a useful epidemiological tool to identify dynamics of transmission of TB by addition of few more probes to identify mutations at specific codons.
Abstract: Setting Department of Microbiology Objective To determine the common mutations responsible for rifampicin resistance in TB cases detected by Xpert MTB/RIF assay Design Results of Xpert MTB/RIF assay performed from 2013 to 2017 were analysed for missing probes in different types of specimens containing rifampicin resistant MTB Results Successful results were obtained in14872 of the total 15129 specimens processed by Xpert MTB/RIF assay, of which 9458 (636%) were sputum and 5414 (364%) were extrapulmonary specimens MTB was detected in 1624 (1717%) sputum and 1121 (2070%) extrapulmonary specimens of which 409 (2518%) and 277 (2471%) were rifampicin resistant respectively Probe E (8382%) was the commonest probe responsible for rifampicin resistance followed by D (393%) and B (379%) Mutation in probe C (029%) was very rare Combination of missing probes like AB (073%), DE (116%) and ADE (014%) was observed 22 (32%) specimens showed presence of all five probes Conclusion Xpert MTB/RIF assay uses various combinations of probe to detect MTB along with rifampicin resistance and is a valuable diagnostic tool It can become a useful epidemiological tool to identify dynamics of transmission of TB by addition of few more probes to identify mutations at specific codons
TL;DR: IL-6 appears to be the major cytokine elaborated by mycobacteria infection as well as play a role in the clinical manifestations and pathological events and hence may function as a potent biomarker of tuberculosis.
Abstract: Background Mycobacterium tuberculosis can grow in hostile intracellular environment of macrophages by actively evading macrophage-associated antibacterial activities. The stress response factor contributes this process by releasing inflammatory cytokine Interleukin 6 (IL-6). IL-6 screening of patients with TB may be useful to monitor the progress of infection and to infer the risk of progression to active disease. Vitamin D has a critical role in the innate immune system, in the circulating metabolite and supports induction of pleiotropic antimicrobial responses, through the production of antimicrobial peptides, particularly cathelicidin and its active metabolite. 1,25-dihydoxyvitamin D, has long been known to enhance immune response to mycobacteria. In this study, we have studied the role of IL-6 and Vitamin D3 in M. tuberculosis. Materials and methods Three groups involved in this study are Control, Category I (newly diagnosed TB) and MDR TB patients. The serum levels of IL-6 and vitamin D3 were measured using chemiluminescence and fully-automated enzyme-linked immunosorbent assay respectively. Results The serum levels of IL-6 were significantly increased, whereas vitamin D3 decreased in TB multidrug-resistant group of patients compared to the newly diagnosed TB patients. Conclusion IL-6 appears to be the major cytokine elaborated by mycobacteria infection as well as play a role in the clinical manifestations and pathological events and hence may function as a potent biomarker of tuberculosis. Since, Vitamin D increases activity of cell-mediated immunity; it can be used as a supplementation during tuberculosis therapy.
TL;DR: A collaborative approach for early diagnosis and management of depression in patients with Tuberculosis (Secondary Prevention) can help decrease the burden of disease and improve outcomes.
Abstract: Introduction Depression is common in Tuberculosis (TB) and associated with adverse outcomes through pathogenic mechanisms and impaired self-care behaviours including reduced treatment adherence. Undiagnosed depression can threaten the robustness of DOTS model despite large public health investment. The Depression-Tuberculosis Syndemic requires collaborative partnership with mental health professionals. Aim To study the evidence base for Depression-Tuberculosis Syndemic. Methodology A Pubmed and Google Scholar search was conducted using the key words “Depression”, “Tuberculosis” and “Syndemic” and abstracts screened for appropriateness and relevance. Result Depression-TB Syndemic is common with a bidirectional relationship. Depression is associated with higher hazard ratio and increased prevalence of TB. Depression is independently associated with higher morbidity, mortality, drug resistance, risk of TB reactivation and community TB transmission. The underlying biopsychosocial mechanism of Depression- Tuberculosis Syndemic includes biological factors like inflammatory cascade, HPA axis dysregulation and psychosocial factors like perceived stigma and treatment non-adherence. Discussion Depression is a poor prognostic factor in TB. The National Mental Health Programme (NMHP) and National Strategic Plan (NSP) for Tuberculosis Elimination (2017–2025) work in independent verticals with no integration at policy or at ground level. This results in lack of identification and appropriate management of depression in patients with Tuberculosis despite repeated contact with health care personnel in DOTS centres. A collaborative approach for early diagnosis and management of depression in patients with Tuberculosis (Secondary Prevention) can help decrease the burden of disease and improve outcomes. Conclusion Depression-TB Syndemic requires collaborative approaches at the program level and at the point of service delivery.
TL;DR: Co-supplementation of antioxidants, along with ATT and inclusion of nutritious diet could be useful to reduce the pathogenesis of PTB and is warranted as a future study for the management ofPTB.
Abstract: Background Pulmonary tuberculosis (PTB) is a highly infectious dreadful disease caused by mycobacterium tuberculosis (MTB). Numerous studies reported free radicals activity, antioxidant status and lipid profile in PTB patients, but previous studies have lacunae in comparing the biochemical variables between before and after anti-tubercular therapy (ATT) supplementation to PTB patients. Hence, the present study was carried out to investigate oxidative stress markers, antioxidant status, lipid profile, liver function markers, and glycoprotein components in pulmonary tuberculosis patients (PTB) patients before and after 60 days of ATT. Methods This is a case-control study carried out with 100 healthy subjects and 110 PTB patients. All the patients diagnosed with sputum test and were positive for acid fast bacilli (AFB) were included for the study. An informed consent was obtained from all the patients. Results Our study found increased levels of oxidative stress markers, decreased enzymatic and non-enzymatic antioxidants, altered lipid profile in PTB patients as compared to healthy subjects before treatment and these levels were restored after clinical improvement with ATT. We also found increased concentrations of liver function parameters and components of glycoprotein in PTB patients. ATT refurbished lipid levels, antioxidant status and oxidative stress markers with decrease in liver function enzymes and glycoproteins in PTB patients. Conclusion Co-supplementation of antioxidants, along with ATT and inclusion of nutritious diet could be useful to reduce the pathogenesis of PTB and is warranted as a future study for the management of PTB.
TL;DR: In the past decade, India has made great strides towards ending TB, but the challenges, especially in a high burden setting, are great, and achieving the authors' ambitious targets and goals will require partnering with all stakeholders including civil society and the community.
Abstract: India has made great progress towards TB prevention and control with the adoption of the National Strategic Plan 2017-2025 with significantly greater allocated resources and high level political commitment. Aligning with the global End TB Strategy, India has announced the target of ending TB by 2025, five years ahead of the rest of the world. The End TB strategy is comprised of a multi-pronged approach incorporating patient-centered care and prevention, bold policies and supportive systems, and intensified research and innovation. In the past decade, India has made great strides towards ending TB, but the challenges, especially in a high burden setting, are great, and achieving our ambitious targets and goals will require partnering with all stakeholders including civil society and the community.
TL;DR: Bedaquiline along with an optimized background regimen has shown early sputum conversion in larger number of difficult to treat patients having additional resistance of second line drugs along with INH and Rifampicin.
Abstract: Background Bedaquiline (BDQ) was approved for treatment of drug resistant TB (DR-TB) under Conditional Access Programme (CAP) of Revised National Tuberculosis Control Programme (RNTCP) and was also implemented in the National Institute of TB and Respiratory Diseases (NITRD). We present early efficacy and safety of BDQ containing regimens for DR-TB. Objective To ascertain the early efficacy and safety of Bedaquline containing regimens in treatment of DR-TB. Methods BDQ containing regimens along with other drugs were designed as per WHO recommendations for DR-TB patients. They were followed up for sputum smear and culture conversion, adverse events during the treatment. Results A cohort of 290 DR-TB patients (Median age-29.77) were initiated on BDQ containing regimens. Of the available Sputum results, smear conversion was seen in 51% and 91% patients at the end of 1st week and 3rd month respectively. Similarly, 93% and 98% patients had culture conversion at the end of 3rd and 6th month respectively. 201 adverse events (AE) including 47 deaths were reported among 109 patients. QTc prolongation was seen in 29% patients but only 4 required discontinuation of BDQ. Lost to follow up of treatment was about 6%. Conclusion Bedaquiline along with an optimized background regimen has shown early sputum conversion in larger number of difficult to treat patients having additional resistance of second line drugs along with INH and Rifampicin. The regimen is feasible in programmatic conditions and is relatively safe.
TL;DR: The CRP serum levels was not significantly different in patients with pulmonary TB who experienced sputum conversion compared to patients without sputUM conversion after two months of anti-tuberculosis drug treatment.
Abstract: Background Pulmonary tuberculosis (TB) produces an inflammatory process of the lung parenchyma. While effective treatment of pulmonary TB and disease resolution processes have an impact on decreasing inflammatory conditions of the pulmonary parenchyma. This stimulates researchers to investigate changes in lung parenchymal inflammatory conditions detected from changes of C-reactive protein (CRP) serum levels pre and post two months of anti-tuberculosis drug treatment. Objectives To know the changes of CRP serum levels in pulmonary TB patients with Acid Fast Bacillus (AFB) smear-positive sputum before and 2 months after receiving anti-tuberculosis drug treatment. Method This study used prospective cohort study design, conducted in pulmonary outpatient unit at Dr. Soetomo General Hospital Surabaya from March to June 2013. Sample size was 30 pulmonary TB patients with AFB smear-positive sputum. AFB sputum grading and CRP serum level was measured before and 2 months after receiving anti-tuberculosis drug treatment. International Union Against Tuberculosis and Lung Disease (IUATLD) scale was used for AFB sputum grading. CRP serum was measured using immunoturbidimetric method. Result The average CRP serum levels of pre anti-tuberculosis drug treatment were 6.48 ± 4.27 mg/dL in males and 6.28 ± 5.26 mg/dL in females. After two months of anti-tuberculosis drug treatment, the average CRP serum levels were 1.21 ± 1.94 mg/dL in males and 1.21 ± 1.22 mg/dL in females. Sputum conversion occurred in 27 out of 30 samples after two months of anti-tuberculosis drug treatment. Conclusion The CRP serum levels was not significantly different in patients with pulmonary TB who experienced sputum conversion compared to patients without sputum conversion after two months of anti-tuberculosis drug treatment.
TL;DR: It is high time when TB control programs must begin to address tobacco control as a potential preventive intervention to combat colliding epidemics of tobacco and tuberculosis.
Abstract: Background Ending the TB epidemic by 2030 is among the key targets for countries to achieve Sustainable Development Goals. In current times we are grappling with dual burden of tuberculosis as well as tobacco use. Methods There is sufficient evidence to establish that tobacco smoking significantly spikes up the risk of acquiring, developing and death among tuberculosis patients. Active or passive exposure to tobacco smoke is significantly associated with tuberculosis infection and tuberculosis disease, independent of a large number of other potential confounders. Results Despite having substantial evidence about the impact of tobacco control measures, particularly tobacco cessation, on TB outcomes, the integration of TB and tobacco control still remains far-off. Conclusion It is high time when TB control programs must begin to address tobacco control as a potential preventive intervention to combat colliding epidemics of tobacco and tuberculosis. This white paper discusses about the role of tobacco control in reaching the ambitious goal of ending TB epidemic by 2030.
TL;DR: Treatment success rate under RNTCP is good but still need to improve, to make it 100 percent, according to the study.
Abstract: Background India accounts for one fourth of the global tuberculosis (TB) burden. In 2015, an estimated 28 lakh cases occurred and 4.8 lakh people died due to TB and proportion of children among new TB patients was 6% in 2016. The clinical presentation of childhood TB is extremely variable, therefore the study attempted to understand, the socio-demographic profile of pediatric tuberculosis patients, and the treatment outcomes under Revised National Tuberculosis Control Program (RNTCP). Methods It was a prospective study carried out from January 2015 to December 2015. A predesigned, pretested and semi-structured questionnaire was used to interview caregivers of pediatric TB patients and they were followed up at two more occasions i.e. at the end of intensive phase at the end of continuation phase. Results A total of 141 study subjects were enrolled. Majority of the subjects (51.8%) belonged to 11–14 years of age group were females (63.8%) and from lower middle class families (48.9%). Extra pulmonary TB (70.2%) was almost three times more prevalent than pulmonary TB. During follow up visits symptoms like chest pain, breathlessness and eye redness were disappeared by the end of intensive phase and fever, cough and skin lesion improved by the end of continuation phase. Mean weight gain in malnourished children (2.6 kg) was lesser as compared to normal children (3.0 kg) at the end of 3rd visit. Treatment success rate in category 1 was 96.2% and in category 2 was 90%. Conclusion Treatment success rate under RNTCP is good but still need to improve, to make it 100 percent.
TL;DR: Perceived stigma among the patients was identified as an important predictor for the adherence to DOTS therapy and in-depth qualitative research is recommended to get more insight on the extent and shape of stigma and the way it influences the adherence.
Abstract: Background Stigma is a major barrier to the successful completion of the Directly Observed Treatment Short Course (DOTS). People put on DOTS have to face repeated exposure to stigma as per the requirement of the treatment. Thus stigma can shape the extent of access and adherence to treatment. But there is very little information available in Indian context explaining the extent of association between the stigma perceived among the patients and adherence to their DOTS therapy. Aim To explore the level of stigma perceived by the persons with TB and its influence on the adherence to DOTS treatment. Methods A cross sectional epidemiological study was conducted among 145 DOTS defaulters from three randomly selected districts in West Bengal. Respondents were approached at their households. Information was collected using a pretested questionnaire. Adherence to DOTS was grouped as early default (continued DOTS from 0 to 30 days) and late default (continued DOTS > 30). Stigma score was assessed using 11 item questions. Stigma score was grouped as low level (0–23) and high level (24–44). Analysis was done using Chi-square and multivariate logistic regression models to identify factors to influence adherence to DOTS. SPSS 23.0 version statistical software was used for analysis. Results Mean stigma score for the state was 23.0. Total 51 (40.69%) persons were within the low stigma group and 94 persons (59.31%) were within high stigma score group. District wise mean score was 19.8, 22.8 and 24.5 respectively for Birbhum, Jalpaiguri and North 24 Parganas. In North 24 Parganas, the high stigma score group accounted for 85.5% compared to 35.9% in Birbhum. Among the low stigma group, late default was 52.1% compared to 66.7% in high stigma group (p = 0.054). People with lower stigma level were 8.59 times more likely to have late default than the people with higher stigma level (p = 0.001). Conclusion Perceived stigma among the patients was identified as an important predictor for the adherence to DOTS therapy. Stigma reduction strategy should be designed to improve adherence to DOTS therapy. Present study recommends in-depth qualitative research to get more insight on the extent and shape of stigma and the way it influences the adherence. Apart from the stigma of the patients, influence of community stigma is a gray area for further research.
TL;DR: The accuracy and approximate cost of various ACF algorithms currently in vogue in India or those which could be useful, while inputting the sensitivity and specificity of screening and diagnostic tools as estimated from recently conducted community based surveys are explored.
Abstract: Community based active case finding (ACF) for tuberculosis (TB) has seen resurrection in the current armamentarium of many TB managers in their fight toward eliminating TB. This article explores the accuracy and approximate cost of various ACF algorithms currently in vogue in India or those which could be useful, while inputting the sensitivity and specificity of screening and diagnostic tools as estimated from recently conducted community based surveys. This analysis informs that ACF may be prioritized to higher prevalence settings and the diagnostic algorithm for specific setting may be chosen taking into account the expected prevalence, estimated accuracy of the algorithm and resource availability. Further, chest X-ray cannot be used alone as a diagnostic tool and can be relied upon for this purpose when at least one of the three sputum specimen is smear positive. Accuracy of Xpert MTB/RIF as a diagnostic tool in community situations needs to be investigated further. The review brings out significant proportions of initial default and default during treatment among cases detected through ACF thus emphasizing the need for heightened efforts toward preventing the same. The article rounds off emphasizing priority to addressing barriers to speedy scale up of more sensitive diagnostic tools for health center based case finding including in private sector and ACF in high risk clinical groups for early and efficient case detection. It concludes by putting forth certain research areas that would strengthen future efforts.