Drug-sensitive Tuberculosis Patients Research Articles

Socio-demographic factors & adherence of newly diagnosed pulmonary tuberculosis patients to the newly introduced daily regimen: A hospital survey based follow up study

IntroductionPoor adherence to anti-tuberculosis medication is a major barrier to its global control. Patient adherence to the standard anti-TB therapy (ATT) in developing countries has been estimated to be as low as 40%. Multiple factors influencing adherence to treatment are:Economic and structural factors such as homelessness, unemployment and poverty; patient related factors like ethnicity, gender, age, knowledge about TB, cultural belief systems, mental state etc. Aims & objectivesThis study was planned with the aim to study the association between various socio-demographic factors with level of adherence to the daily regimen amongst newly diagnosed pulmonary TB patients at a tertiary care hospital in metropolitan city of Maharashtra. Additionally, we tried to determine the type of non-adherence along with reasons for it. Methodology: An interview based pre-tested and validated questionnaire was developed & used as data collection tool. Total 181 newly diagnosed, FDC naïve, drug sensitive pulmonary TB patients from DOT center of a tertiary care hospital were enrolled & interviewed for sociodemographic, treatment & adherence details. They were followed up at 2nd & 6th month of their treatment, i.e., IP & CP follow up. Their Nikshay portal data & TB treatment cards were accessed for information on treatment adherence. ResultsOut of 181 patients, 110 (60.8%) were found to be adherent whereas 71 (39.2%) were found to be non-adherent. Among those non-adherent, 64 (90.9%) had treatment gaps (intermittent missed doses) & 7 (9.9%) showed discontinuation of treatment. Majority of these patients reported personal obligations & starting to feel better as the main reason for non-adherence (p < 0.0001). The sociodemographic factors that had significant impact on level of adherence were patients’ age (p = 0.013); level of education (p = 0.035); family size (p = 0.018); family history of TB (p = 0.0001) & current smoking habit (p = 0.025). ConclusionIt is evident from the study that socio-demographic factors do have a major impact on patients’ levels of adherence to treatment. Family history of TB as well as sputum conversion at end of treatment/CP have been identified as independent risk factors among pulmonary TB patients who are non-adherent to treatment. Thus, ensuring robust availability of DBT & intensive tobacco cessation sessions for all diagnosed patients as well as strengthening system for making prophylaxis available for household & close contacts of patients can help in reducing impact of socio-demographic factors & improving adherence levels. RecommendationsIn-patient care option specifically during IP; regular dietary counseling to improve nutrition & help reduce drug side effects & use of alternate adherence technologies like facility-based DOT or Video Observed Therapy (VOT) wherever feasible can help to improve adherence levels for TB patients from all walks of life.

Uptake and Completion of Tuberculosis Preventive Treatment Using 12-Dose, Weekly Isoniazid-Rifapentine Regimen in Bangladesh: A Community-Based Implementation Study.

The United Nations high-level meeting (UNHLM) pledged to enroll 30 million in tuberculosis preventive treatment (TPT) by 2022, necessitating TPT expansion to all at tuberculosis (TB) risk. We assessed the uptake and completion of a 12-dose, weekly isoniazid-rifapentine (3HP) TPT regimen. Between February 2018 and March 2019 in Dhaka, community-based TPT using 3HP targeted household contacts of 883 confirmed drug-sensitive pulmonary TB patients. Adhering to World Health Organization guidelines, contacts underwent active TB screening before TPT initiation. Of 3193 contacts who were advised health facility visits for screening, 67% (n = 2149) complied. Among these, 1804 (84%) received chest X-rays. Active TB was diagnosed in 39 (2%) contacts; they commenced TB treatment. Over 97% of 1216 contacts began TPT, with completion rates higher among females, those with more education and income, non-slum residents, and those without 3HP-related adverse events. Adverse events, mainly mild, occurred in 5% of participants. The 3HP regimen, with its short duration, self-administered option, and minimal side effects, achieved satisfactory completion rates. A community-focused TPT approach is feasible, scalable nationally, and aligns with UNHLM targets.

Internalized social stigma and its determinants among drug-sensitive tuberculosis patients in Armenia

Abstract Background Internalized social stigma (ISS) is still an issue among tuberculosis (TB) patients, exacerbating their suffering and affecting their treatment compliance. Quantitative studies of TB-related ISS are scarce. This study sought to measure ISS and identify its predictors among primary drug-sensitive TB patients in Armenia. Methods All patients throughout Armenia diagnosed with drug-sensitive TB from Apr, 2019 through Feb, 2021 were targeted for baseline and follow-up interviews at the start of their TB treatment and shortly after completing it, respectively. The instrument included domains on patient's social support, TB knowledge, health, and stigma. ISS was measured via a 10-item scale previously used in Armenia, with the total score ranging from 10 to 50. Fitted linear regression models identified predictors of ISS at each assessment. Results Overall, 401 patients were interviewed at the baseline and 285 at the follow-up. Between the assessments, patient's ISS score decreased from 27.4 to 23.8 (p &amp;lt; 0.01). Factors related to higher stigma at the baseline included age (B = 0.13, p &amp;lt; 0.01), rural residence (B = 1.56, p &amp;lt; 0.05), depression (B = 2.46, p &amp;lt; 0.01), frequent alcohol use (B = 2.67, p &amp;lt; 0.01), and higher stigma in the family (B = 0.55, p &amp;lt; 0.01), while socioeconomic status score was protective against ISS (B = (-0.74), p &amp;lt; 0.01). The fitted model explained 33.4% of the ISS score variance. Age and depression were related to higher ISS score at the follow-up as well, while quality of life score (B = (-5.27), p &amp;lt; 0.01), family support score (B = (-0.53), p &amp;lt; 0.01), and receiving psychological counseling/education (B = (-2.04), p &amp;lt; 0.05) were protective against ISS. Conclusions This study found rather high levels of ISS both at the time of TB diagnosis and after the treatment course. It also pointed out several factors that could be targeted to reduce ISS, including educating TB patients and their family members, providing them timely psychological counseling and financial support. Key messages • During TB treatment, ISS decreased significantly. Modifiable factors protective against ISS included more support in the family and family's satisfactory financial status. • After the treatment, ISS score was significantly lower among those patients who received psychological counseling and education on TB at the treatment start compared to those who did not receive it.

Factors affecting ability of TB patients to follow treatment guidelines – applying a capability approach

BackgroundNegotiating anti-Tuberculosis treatment is a complicated process comprising daily consumption of multiple medications at stipulated times and dosages, as well as periodic follow-ups and investigations, may not be uniform for all Tuberculosis (TB) patients and some may perform better than others. In this context, we conducted a study in Thiruvananthapuram district, Kerala to ascertain the ability of those suffering from TB to follow treatment guidelines.MethodsThis study used an embedded mixed methods design. We collected cross-sectional data from 135 drug sensitive pulmonary TB patients aged 18 years or above in Thiruvananthapuram, Kerala using a structured questionnaire to get the proportion of patients following all treatment guidelines. We also did eight in-depth interviews (four men and four women) from within the survey sample. The in-depth interviews were inductively analysed for getting deeper insights about reasons for the choices people made regarding the treatment guidelines. Written informed consent was taken from all participants and the study was implemented after the necessary programmatic and ethical clearances.ResultsOf the 105 men and 30 women studied, uninterrupted daily drug consumption was reported by 80 persons (59.3%, 95% Confidence Intervals (CI) 50.8-67.2%). Overall, 38 (28.2%, 95% CI 21.3%-36.3%) persons were able to follow all seven aspects of advised guidelines. Living in an extended/ joint family (Adjusted Odds ratio (AOR) 2.6, 95% CI 1.1-6.0), approximate monthly household expenditure of over rupees 13,500 (AOR 2.9, 95% CI 1.3–6.7) and no perceived delay in seeking initial care (AOR 3.2, 95% CI 1.2–8.7) were significantly associated with following all aspects of treatment guidelines. In-depth interviews revealed reflective treatment related behaviours were influenced by bodily experiences, moral perceptions, social construct of TB, programmatic factors and substance use. Sometimes behaviours were non-reflective also. Programmatic stress was on individual agency for changing behaviour but capability and opportunity for these were influenced social aspects like stigma, gender roles and poverty.ConclusionTB patients live amidst a syndemic of biomedical and social problems. These problems influence the capabilities and opportunities of such TB patients to follow treatment guidelines. Interventions should balance focus on individual agency and social abd economic factors.

Assessment of anxiety and depression among tuberculosis patients of Ahmedabad, India

BackgroundIndia has high prevalence of Tuberculosis (TB). The long duration of treatment and chronic nature of illness predispose a person to anxiety as well as depression. Various addiction habits may affect treatment outcome and impact mental wellbeing in TB patients. This study was planned with the objectives of finding prevalence of anxiety and depression in tuberculosis patients at Ahmedabad district and to find association between anxiety, depression and different variables of TB patients as well as to assess the addiction profile of TB patients. MethodsA total of 600 TB patients above 18 years and having completed 3 months of anti TB treatment without any psychiatric illness were selected randomly from 3 types of health institutes where patients receive treatment namely Ahmedabad district TB center (Institute 1), one medical college attached hospital (Institute 2) and one private hospital (Institute 3).Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression. ResultsThe mean age of study patients was 41.57 ± 13.44 years and 66.3% (398) patients were males. The prevalence of anxiety and depression was found to be 37.5% and 41.2% respectively while in 18.66% patients both anxiety and depression coexisted simultaneously. Institute 1 reported highest prevalence of anxiety (45.4%) while institute 2 reported highest prevalence of depression (42.9%). The prevalence of anxiety among drug sensitive TB patients was 32.7% while among drug resistant TB patients was 80%.The prevalence of depression in drug sensitive TB patients was 37.03% while among drug resistant TB patients was 78.3%. Anxiety had a statistically significant association with gender, occupation, socioeconomic class, type of TB, site of TB and perceived social isolation (p < 0.05).Except gender, depression was significantly associated with all the variables (p < 0.05).Tobacco addiction was found in 37.5% patients, alcohol addiction in 8.3% while 4.5% patients had both types of addiction. There was a statistically significant association found between addiction and variables like gender, residence, occupation, type of TB and site of TB. ConclusionOne third of patients had anxiety and more than one third had depression in which the prevalence of depression was higher than anxiety. District TB Center had highest prevalence of anxiety while medical college attached hospital had highest prevalence of depression. Anxiety and depression were higher in drug resistant TB patients. Tobacco addiction was more common than alcohol. Addiction had a significant association with depression, nonworking rural males and patients who had drug resistant pulmonary TB.

Prevalence of Stigma Among TB Patients and Its Associated Factors - A Community Based Cross-Sectional Study in Puducherry, India

Background: Tuberculosis (TB) is a disease that has both medical as well as social dimensions. Stigma and associated discrimination experienced by persons affected by TB is a barrier to the interventions towards TB elimination. A better understanding of stigma will improve the effectiveness of the interventions aimed to alleviate the effects of TB stigma. The objectives were to measure the prevalence of self, anticipated, experienced stigma and its associated factors and to explore the impact of tuberculosis related stigma among TB patients. Methodology: A cross-sectional study was conducted in Puducherry district, Southern India among 420 adult drug sensitive non-HIV TB patients registered under NTEP. Data was collected by face-to-face interview using standardised questionnaire. Results: The mean(±SD) age of the study participants was 44.5 (±15.03) years. Majority were males (267, 63.6%) and were married (330, 78.6%). The prevalence of stigma among TB patients was found to be 69.3%. Perceived stigma was noted in 47.1%, 33.6% had self- stigma and 26.0% had experienced stigma. On measuring the impact of stigma, 52.6% reported participation restriction. Illiteracy and lower-socio economic status were found to be significantly associated with TB stigma. Conclusions: Stigma among TB patients was high. Tailored patient-centric interventions to address stigma and discrimination using culturally appropriate and locally available resources are necessary.

Counseling intervention improves treatment adherence among newly diagnosed drug sensitive Tuberculosis patients of Ahmedabad city – A mixed methods approach

IntroductionCounselling sessions based on the health behaviour module for patients on TB treatment may help improve the level of understanding of tuberculosis and its treatment, importance of adherence to therapy, possible side effects, dietary habits and to address any misconceptions; leading to better adherence and improved outcome. Hence, study attempted to assess the impact of brief counselling intervention through treatment adherence supportive activist (TASA) in improving adherence to treatment among drug sensitive TB patients. MethodsAn explanatory mixed methods design (QUAN-Qual) was carried out. Out of 23 Tuberculosis units (TUs) in Ahmedabad Municipal Corporation (AMC) two were selected, one interventional group where trained counsellor was recruited while other was the control group. All drug sensitive TB patients diagnosed at both selected TUs during January to March 2020 were included in the study. Among all patients who were non-adherent in both the TUs, 14 were selected to explore factors contributing to non-adherence to treatment. ResultsAt the end of intensive phase, drug adherence in the study TU was 85.71% while it was 67.5% in the control TU. At the end of one month of treatment, the proportion of patients having better level adherence was more among counselled patients as compared to non-counselled patients. Marital status, religion, gender did not affect the level of adherence. Reasons for non-adherence as well as perceived barriers to adherence to TB treatment were treatment related, patient related and social barriers. ConclusionDedicated NTEP counsellor (TASA) can help improve the treatment adherence and impact of physical counselling.

Tuberculosis Monitoring Encouragement Adherence Drive (TMEAD): Toward improving the adherence of the patients with drug-sensitive tuberculosis in Nashik, Maharashtra.

Adherence to tuberculosis (TB) medication is one of the critical challenges to tuberculosis elimination in India. Digital adherence technologies (DAT) have the potential to facilitate medication adherence and monitor it remotely. Tuberculosis Monitoring Encouragement Adherence Drive (TMEAD) is one such DAT piloted in Nasik, Maharashtra, from April 2020 to December 2021. The study aims to assess the adherence and cost-effectiveness of TMEAD compared to the standard of care among patients with drug-sensitive tuberculosis (DSTB) residing in the urban areas of Nasik, Maharashtra, India. A quasi-experimental study was conducted among new cases of TB as per the National TB Elimination Programme (NTEP) residing in the urban geography of Nasik. The intervention and control arms were purposively selected from non-contaminating TB units (TUs). A total of 400 DSTB patients (200 in the intervention group and 200 in the control group) were enrolled. After enrolment, patients in the intervention arm were provided with the TMEAD device and followed for 24 weeks to assess treatment outcomes. Adherence was measured as those patients who have completed 80% of prescribed doses, as reported during patient follow-up, and further validated by analyzing the trace of rifampicin in urine among 20% of patients from both arms. A budget impact analysis was done to assess the impact of the TMEAD program on the overall state health budget. Out of 400 enrolled DSTB patients, 261 patients completed treatment, 108 patients were on treatment, 15 patients died, and 16 patients were defaulters over the study period. The study reported overall treatment adherence of 94% among those who completed treatment. Patient reports indicated high levels of treatment adherence in the intervention group (99%) as compared to the control group (90%). Adherence assessed through analyzing trace of rifampicin in the urine sample for the intervention arm was 84% compared to the control arm (80%). Per beneficiary (discounted) cost for TMEAD was Indian rupees (INR) 6,573 (USD 83). The incremental cost-effectiveness ratio of the intervention is INR 11,599 (USD 146), which shows that the intervention is highly cost-effective. This study revealed that patient-reported treatment adherence was high in TMEAD when compared to standard therapy of care for DSTB patients and the intervention is cost-effective. TMEAD could complement the national strategy to end TB by improving adherence to the treatment regimen in India.

Characteristics and contributing factors of adverse drug reactions: an analytical study of patients with tuberculosis receiving treatment under the National TB Program of India

Background Tuberculosis (TB) continues to pose a serious threat to the public health system in India. Although the National Tuberculosis Elimination Program (NTEP) is providing a wide range of interventions from early diagnosis to complete treatment to reduce morbidity and mortality from TB, adverse drug reactions (ADR) remain a challenge in treatment adherence and completion. Methods An observational cross-sectional study was conducted in selected districts of Gujarat state. A total of 593 reported TB patients were recruited with an adjusted unified distribution based on the type of cases, site of diseases, and service facility through a simple random sampling method. A semi-structured questionnaire tool was used to collect socio-demographic, clinical, and ADR-related data from the TB patients. Data was analyzed for the frequency, percentage, chi-squared, and adjusted odds ratio to find the association between the variables. Results The majority of the study participants were male (87.2%), aged 15 to 60 (57.8%), daily laborers (22.4%), and married (64.2%). Over 75% of individuals had pulmonary TB, with 87% having experienced their first episode, 83% being new cases, and 44.7% having a history of addiction. ADR with mild symptoms was reported by more than a quarter (29%) of TB patients during the intensive phase (77%). The association between ADR experience and drug susceptibility was significant (p&lt;0.005) and drug-resistant TB patients experience two times more ADRs than drug-sensitive TB patients (OR 2.04). Binomial logistic regression was carried out to describe the association between various variables and occurrence of ADRs. Conclusion The study highlighted a need to enhance health care providers’ capacity and program structure for managing ADRs among TB patients. In order to completely eliminate TB across the country, it also emphasized the attention for a holistic and all-encompassing strategy for managing TB patients at the field level.

Level of adherence to anti-tubercular treatment among drug-sensitive tuberculosis patients on a newly introduced daily dose regimen in South India: A cross-sectional study.

Tuberculosis (TB) patients on the National Tuberculosis Elimination Program (NTEP) treatment protocol receive daily doses without health professional-supervised drug intake as during the previous directly observed treatment short-course (DOTS) regimen. We aimed to measure the level of adherence to anti-tubercular treatment (ATT) and the reasons for non-adherence among drug-sensitive TB patients on a daily-dose regimen in South India. A cross-sectional study was conducted among TB patients who received ATT as part of the standard treatment protocol in NTEP. Patients were interviewed to capture their understanding of TB, adherence, and the reason for non-adherence to ATT using validated instruments. Urine drug metabolite testing was performed using the high-performance liquid chromatography (HPLC) technique to confirm adherence. A total of 488 patients were recruited for the study. 64.8% of patients had 'good knowledge' about TB and ATT. According to the subjective report, 63.7% of patients were adherent, but urine drug metabolite testing revealed 53.4% adherence. A statistically significant difference (p< 0.05) exists between subjective and objective adherence measures. Patient-reported reasons for non-adherence were side effects of ATT (18.6%), loss of daily wages (15.0%), and forgetfulness (10.0%), among others. Nearly half of the patients were non-adherent to the daily dosing regimen. Adherence as reported by the patients is unreliable, and urine testing could be used in routine care to assess adherence. CTRI/2020/04/024941.

Determinants Of Treatment Adherence In Drug-Sensitive Tuberculosis Patients During The Covid-19 Pandemic

Background: During the COVID-19 pandemic in Surakarta, there were patients who were absent, failed, and dropped out of treatment. This study aims to analyze factors associated with treatment adherence of drug-sensitive tuberculosis patients (TB-SO) during the COVID-19 pandemic at the Surakarta City Public Health Center.&#x0D; Methods: This research method combines quantitative research with cross-sectional research. A sample of 105 patients from 10 Public Health Center (Puskesmas) in Surakarta City was obtained using a total population sampling based on inclusion and exclusion criteria. This research was conducted from April to June 2022. The research instrument used was a questionnaire, and the data was analyzed univariate and bivariate with the chi-square.&#x0D; Results: This study showed that more patients were adherere (79%) than non-adherent (21%). Factors related to treatment adherence were the role of health professionals (p = 0.045) and Treatment Supervisors (Pengawas Menelan Obat/PMO) support (p = 0.035).&#x0D; Conclusion: The role of health workers and the support provided by the PMO to patients related to adherence to treatment for TB-SO patients Therefore, it is expected that health professionals need to keep a good relationship with patients through personal counseling and need to provide socialization to PMOs.

Fluoroquinolone Derivatives in the Treatment of Mycobacterium tuberculosis Infection.

Tuberculosis (TB) is currently one of the leading causes of death due to infective agents, and the growing rate of multidrug-resistant tuberculosis (MDR TB) cases poses an emergent public health threat. Fluoroquinolones are commonly used in the treatment of both MDR TB and drug-sensitive tuberculosis patients who are intolerant to first-line antitubercular agents. Unfortunately, these drugs have mild side effects, relevant to the prolonged treatment regimens and diminished bioavailability due to binding of metal ions. Moreover, the resistance to fluoroquinolones is also on the rise, a characteristic of extensively drug-resistant TB (XDR TB). Here, we developed esters as prodrugs of the fluoroquinolones levofloxacin and ciprofloxacin, with long-chain fatty alcohols. Both the alcohols and the quinolone have previously shown antimycobacterial activity and the aim was to develop esters with improved lipophilicity and capable of delivering the free acid inside mycobacterial cells. The carboxylic acid group of fluoroquinolones is essential to the mode of action but is also responsible for many of its side effects and metal-chelating properties. The synthesis, stability in biological media, and antibacterial activity were evaluated, the latter not only against Mycobacterium tuberculosis but also against other clinically relevant bacterial species, since the parent compounds display a broad spectrum of activity. The biological results show a reduction in the antitubercular activity of the synthesized derivatives, probably due to deficient activation of the ester prodrug. Despite this, it was found that the derivatives exhibit bioactivity against other fluoroquinolone-resistant bacteria, indicating a different mode of action and suggesting that it may be worthwhile to research further modifications to the carboxylic acid group. This might lead to new compounds that are efficient against resistant strains. This idea that the compounds may act by a different mechanism of action was further supported by a brief computer investigation that demonstrated the potential lack of selectivity of the esters to the fluoroquinolone target.

Factors Influencing Treatment Adherence Among Drug-Sensitive Tuberculosis (DS-TB) Patients in Armenia: A Qualitative Study

PurposeDespite the availability of effective treatment, tuberculosis (TB) is still one of the leading causes of mortality around the globe. Poor adherence to treatment challenges TB management both globally and locally. Proper adherence to treatment contributes to successful outcomes and prevents the development of drug-resistant forms of TB.Patients and MethodsWe conducted a qualitative study to identify and describe the factors that facilitated treatment adherence among drug-sensitive TB (DS-TB) patients in Armenia. Sixteen in-depth interviews (IDIs) with former DS-TB patients, two IDIs with family members of former DS-TB patients, and a focus group discussion with healthcare providers who manage DS-TB patients were conducted. The educational and ecological assessment component of the PRECEDE-PROCEED model was applied as a conceptual framework to guide the interview content and data analysis.ResultsFormer patients’ awareness of TB and its treatment, beliefs about TB, trust in TB healthcare providers, and a sense of responsibility were the most common factors that predisposed them to complete the treatment. Support received from providers, family, and friends, a desire to avoid TB-associated stigma, and good tolerance of TB medications were the main reinforcing factors. Enabling factors included a relatively simple regimen of TB treatment and accessibility and affordability of TB services.ConclusionThe findings of the study provide new perspectives on factors that facilitate adherence to long-term therapies, such as TB. Interventions that aim to invoke a patient’s sense of responsibility and positive beliefs about TB as well as engage families might promote the successful completion of treatment.

Association of IL – 23 R rs 7518660 Gene Polymorphism with Susceptibility and Disease Severity of Pulmonary Tuberculosis

Pulmonary Tuberculosis (TB) is a global health problem. Of all people infected with Mycobacterium tuberculosis only a small proportion develops into TB. IL 23 is the key cytokine in the pathogenesis of TB infection. This study aims to determine the association of IL-23 R rs 7518660 gene polymorphism with susceptibility and disease severity of Pulmonary TB. A case control study involved 105 people consisting of 31 drug sensitive pulmonary TB patients, 40 patients with drug-resistant pulmonary TB and 34 healthy subjects as a control. IL-23 R rs 7518660 gene polymorphism G allele increases susceptibility to both TB drug-sensitive and drug-resistant. G and A allele, AA and AG genotypes indicates (p value &gt;0.05) in correlation with disease severity based on lesion in chest x-ray and high load of Mycobacterium tuberculosis in sputum. There was a significant relationship between allele A and susceptibility to pulmonary TB with an odds ratio of 0.231. It showed that patients with A alleles (AG and AA genotypes) were at risk of developing TB by 1/0.231 = 4.33 times lower than patients with GG genotypes. Meanwhile, the relationship of the G allele with susceptibility to pulmonary TB obtained (p value &lt;0.05) and an odds ratio value of 0.127 indicating that patients with G alleles (GG and AG genotypes) were at risk of developing TB of 1/0.127 = 7.87 times higher than in patients with the AA genotype. Conclusion: We found significant correlation between IL-23 R rs 7518660 gene polymorphism G allele with susceptibility to pulmonary TB, but the result was not significant with disease severity.

BLOCKING PD-1 RESCUES PROTECTIVE T CELL RESPONSE TO FACILITATE BACILLARY CLEARANCE AND MODULATION OF THE EFFLUX PUMP EXPRESSION OF MYCOBACTERIUM TB

TYPE: Late Breaking Abstract TOPIC: Chest Infections PURPOSE: Previously, we have shown the critical role of regulatory Treg cells and PD-1 pathway in causing suppressed state of Tcell response against Mycobacterium tuberculosis among TB patient. In this study, we attempted to understand the status of host immune response among the MDR and Drug Sensitive TB patients. We also checked the contribution of PD-1 pathway on poly-functional Tcells,critical for protective immunity in TB. METHODS: For immune response profile and invitro experiments, polychromatic flowcytometry based immunological assays were performed.PD1 blocking experiments were performed in mice infected with Mtb. RESULTS: We observed rescue of PFTS in TB patients by blocking PD-1.We also observed that PFTs (IFN-γ+ TNF-α+) undergo apoptosis in TB patients due to higher expression of PD-1.Blocking PD-1 pathway in vivo among mice infected with Mtb, demonstrated restoration of PFTs with enhanced reduction of bacillary load. We observed increase in the frequency of Tregs whereas decrease in the PFTs response in Drug Resistant as compared to Drug Sensitive TB patients. Furthermore, we observed modulation of efflux pump of M.tb by pro-inflammatory (IFN-γ , TNF-α) and anti-inflammatory cytokines (IL-10 and TGF-β) in invitro MDM model. CONCLUSIONS: Our results demonstrate elicitation of weaker effector T cell response in DR TB compared to DS TB patients.Our results showed that rescuing appropriate immune response improves the efficacy of anti-tubercular therapy in TB. CLINICAL IMPLICATIONS: Our findings suggest critical role of PD-1 in suppressing the protective immune response in TB. Rescuing PFTs by blocking PD-1 pathway may offer a novel strategy for adjunct immunotherapy in TB. DISCLOSURE: Nothing to declare. KEYWORD: Tuberculosis PD1 Regulatory T cells Polyfunctional T cells

A social networks-driven approach to understand the unique alcohol mixing patterns of tuberculosis patients: reporting methods and findings from a high TB-burden setting

Individuals who consume alcohol have a higher chance of contracting tuberculosis (TB) due to their social mixing patterns. We aimed to study the social mixing patterns of TB patients who consume alcohol on a regular basis using a quantitative social network approach. In a high-TB prevalence context in India, a social network survey of 300 newly diagnosed pulmonary drug-sensitive TB patients was done. The survey found 52 (17%) male TB patients who shared alcohol on a regular basis with 106 (4%) of their first-degree social contacts. Alcohol sharing happened in 16 neighborhood venues. When compared to contacts who did not use alcohol, a higher proportion of contacts with regular alcohol use were diagnosed with TB (12.3%; 95% CI: 6.6–20.00 vs. 3.5%; 95% CI: 2.8–4.3). Social network analysis showed that the network consisting of patients and contacts was less dense and less connected (with density ratio of 0.009, and degree centrality of 1.3, and betweenness centrality of 0.5), indicating weaker transmission potential of the network. Comparatively the network consisting of patients, contacts and their alcohol sharing venues was more dense and more connected (with density ratio of 0.018, higher degree centrality of 3.1 and betweenness centrality of 154.2) indicating stronger transmission potential of the network. Regular alcohol sharing in four venues created a giant network component, that linked a higher proportion of contacts without TB (72.3%) to a higher proportion of TB patients (67.3%) and their contacts with TB (38.4%). When examined from a network perspective, the pooled TB transmission exposure of contacts with regular alcohol use grew by a factor of 10, which helped explain the unfavorable social mixing of patients and contacts with regular alcohol use.

Outcomes and predictors of tuberculosis mortality in Kweneng West District, Botswana: a retrospective cohort study

IntroductionBotswana is among the countries with the highest tuberculosis (TB) notification rates in the world. However, there is paucity of data on the outcomes and predictors of TB mortality at district level in Botswana. This study was aimed at describing the TB outcomes and identifying the predictors of mortality in Kweneng West district, Botswana.Methodsthis was a retrospective cohort study of TB outcomes in Kweneng West, from January 2008 to December 2016. All documented drug-sensitive TB (DS-TB) patients aged 16 years and above were included. The World Health Organization (WHO) definitions of treatment outcomes for DS-TB were used. Binary logistic regression was used to identify predictors of mortality.Resultsthere were 1475 TB notifications in the study period. The median age was 36 years and 41.5% were female. A total of 728 (49.4%) were HIV positive. Pulmonary TB (PTB) accounted for 87.3% of all cases. The overall treatment success rate (TSR) was 81.9% and the mortality rate was 9.4%. Compared to the 16-25 years age group, patients aged more than 65 years had the highest risk of mortality (AOR=9.63). Other significant predictors of mortality were male sex (AOR=1.63), no sputum microscopy (AOR=1.77), positive HIV (AOR=2.13) and unknown HIV status (AOR=4.47). Positive sputum microscopy (AOR=0.50) and extra-pulmonary TB (EPTB) (AOR=0.56) were associated with less mortality.Conclusionwhile Botswana has relatively good TB treatment success rates, the mortality rates are high. Public health interventions should target the identified risk factors of mortality.

Evaluation of Diagnostic Value of Mediastinum for Differentiation of Drug Sensitive, Multi and Extensively Drug Resistant Tuberculosis Using Chest X-Rays

Background and ObjectiveThe rise of Drug Resistant Tuberculosis (DR TB), particularly Multi DR (MDR), and Extensively DR (XDR) has reduced the rate of control of the disease. Computer aided diagnosis using Chest X-rays (CXRs) can help in mass screening and timely diagnosis of DR TB, which is essential to administer proper treatment regimens. In CXRs, lungs and mediastinum are two significant regions which contain the information about the likelihood of DR TB. The objective of this work is to analyze the shape characteristics of lungs and mediastinum to improve the diagnostics accuracy for differentiation of Drug Sensitive (DS), MDR and XDR TB using computer aided diagnostics system. MethodsThe CXR images of DS and DR TB patients are obtained from a public database. The lung fields are segmented from the CXRs using Reaction Diffusion Level Set Evolution. Mediastinum is segmented from the delineated lung masks using Chan Vese model. The shape features from each lung and mediastinum masks are extracted and analysed. The discriminative power of individual and combination of both lung and mediastinum features are evaluated using machine learning techniques for classification of DS vs MDR, MDR vs XDR and DS vs XDR TB images. The performances of classifiers are compared using standard metrics. ResultsThe proposed segmentation methods are able to delineate lungs and mediastinum from the CXR images. The extracted lung and mediastinum features are found to be statistically significant (p < 0.05) for differentiation of DS and DR TB conditions. Using the combination of both lung and mediastinum features, Multi-Layer Perceptron classifier achieves maximum F-measure of 82.4%, 81.0% and 87.0% for differentiation of DS vs MDR, MDR vs XDR and DS vs XDR, respectively. ConclusionAnalysis of mediastinum along with the lungs in chest X-rays could improve the diagnostic performance for differentiation of drug sensitive and resistant TB conditions. The proposed methodology is able to differentiate DS, MDR and XDR TB, and found to be clinically relevant. Hence, this work is useful for computer-based early detection of DS and DR TB conditions.

Factors predicting self-report adherence (SRA) behaviours among DS-TB patients under the \u201cIntegrated model\u201d: a survey in Southwest China

BackgroundChina is one of 30 countries with a high tuberculosis (TB) burden, and poor adherence to TB treatment is one of the biggest challenges for TB control. We aimed to explore the barriers and facilitators of treatment adherence among drug-sensitive tuberculosis (DS-TB) patients under the “Integrated model” in Western China, to provide evidence-based treatment and control regimens for DS-TB patients to improve adherence behaviours.MethodsBoth qualitative and quantitative research methods were used to explore the factors associated with self-reported adherence (SRA) behaviours. Questionnaire surveys with DS-TB patients and in-depth interviews with leaders from the Centers for Disease Control and Prevention (CDC) and community health sectors (CHCs), healthcare workers (HCWs) from CHCs, and DS-TB patients were conducted.ResultsA total of 459 eligible patients were included in the quantitative survey, and two patients and 13 healthcare providers were included in the in-depth interviews. The percentage of patients who experienced a missed dose, lack of follow-up sputum examination, and interrupted treatment were 19.0%, 11.3%, and 9.2%, respectively. Patients aged 20–39 had a higher risk of missed dose [OR (95% CI): 2.302 (1.001–5.305)] and a lower risk of interrupted treatment [OR (95% CI): 0.278 (0.077–0.982)] than patients more than 60 years. Patients who were of Han ethnicity (OR [95% CI]: 0.524 [0.301–0.912]) received psychological support (OR [95% CI]: 0.379 [0.144–0.998]) from their family and had a lower risk of missed doses. Patients who had drug side effects had a higher risk of interrupted treatment (OR [95% CI]: 2.587 [1.237–5.412]). Patients who possessed higher knowledge had a lower risk of lack of follow-up sputum examination [OR (95% CI): 0.817 (0.673–0.991)]. The results of the qualitative study also reported that patients’ poor TB knowledge was the main reason for their non-SRA behaviours.ConclusionsPatient-centred strategies should be implemented to improve health literacy and strengthen psychological support. More effective case management should be designed and implemented based on different patient characteristics to improve adherence behaviours in further studies.

Expansion of social protection is necessary towards zero catastrophic costs due to TB: The first national TB patient cost survey in the Philippines.

Tuberculosis (TB) is a disease associated with poverty. Moreover, a significant proportion of TB patients face a substantial financial burden before and during TB care. One of the top targets in the End TB strategy was to achieve zero catastrophic costs due to TB by 2020. To assess patient costs related to TB care and the proportion of TB-affected households that faced catastrophic costs, the Philippines National TB Programme (NTP) conducted a national TB patient cost survey in 2016-2017. A cross-sectional survey of 1,912 TB patients taking treatment in health facilities engaged with the NTP. The sample consists of 786 drug-sensitive TB (DS-TB) patients in urban facilities, 806 DS-TB patients in rural facilities, and 320 drug-resistant TB (DR-TB) patients. Catastrophic cost due to TB is defined as total costs, consisting of direct medical and non-medical costs and indirect costs net of social assistance, exceeding 20% of annual household income. The overall mean total cost including pre- and post-diagnostic costs was US$601. The mean total cost was five times higher among DR-TB patients than DS-TB patients. Direct non-medical costs and income loss accounted for 42.7% and 40.4% of the total cost of TB, respectively. More than 40% of households had to rely on dissaving, taking loans, or selling their assets to cope with the costs. Overall, 42.4% (95% confidence interval (95% CI): 40.2-44.6) of TB-affected households faced catastrophic costs due to TB, and it was significantly higher among DR-TB patients (89.7%, 95%CI: 86.3-93.0). A TB enabler package, which 70% of DR-TB patients received, reduced catastrophic costs by 13.1 percentage points (89.7% to 76.6%) among DR-TB patients, but only by 0.4 percentage points (42.4% to 42.0%), overall. TB patients in the Philippines face a substantial financial burden due to TB despite free TB services provided by the National TB Programme. The TB enabler package mitigated catastrophic costs to some extent, but only for DR-TB patients. Enhancing the current social and welfare support through multisectoral collaboration is urgently required to achieve zero catastrophic costs due to TB.