Drug-sensitive Tuberculosis Patients Research Articles

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 >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 <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.

Determinants, risk factors and spatial analysis of multi-drug resistant pulmonary tuberculosis in Jodhpur, India

This study was planned to estimate the proportion of confirmed multi-drug resistance pulmonary tuberculosis (TB) cases out of the presumptive cases referred to DTC (District Tuberculosis Center) Jodhpur for diagnosis; to identify clinical and socio-demographic risk factors associated with the multidrug-resistant pulmonary TB and to assess the spatial distribution to find out clustering and pattern in the distribution of pulmonary TB with the help of Geographic Information System (GIS). In the Jodhpur district, 150 confirmed pulmonary multi-drug resistant tuberculosis (MDR-TB) cases, diagnosed by probe-based molecular drug susceptibility testing method and categorized as MDR in DTC's register (District Tuberculosis Center), were taken. Simultaneously, 300 control of confirmed non-MDR or drug-sensitive pulmonary TB patients were taken. Statistical analysis was done with logistic regression. In addition, for spatial analysis, secondary data from 2013-17 was analyzed using Global Moran's I and Getis and Ordi (Gi*) statistics. In 2012-18, a total of 12563 CBNAAT (Cartridge-based nucleic acid amplification test) were performed. 2898 (23%) showed M. TB positive but rifampicin sensitive, and 590 (4.7%) showed rifampicin resistant. Independent risk factors for MDR TB were ≤60 years age (AOR 3.0, CI 1.3-7.1); male gender (AOR 3.4, CI 1.8-6.7); overcrowding (AOR 1.6, CI 1.0-2.7); using chulha (smoke appliance) for cooking (AOR 2.5, CI 1.2-4.9), past TB treatment (AOR 5.7, CI 2.9-11.3) and past contact with MDR patient (AOR 10.7, CI 3.7-31.2). All four urban TUs (Tuberculosis Units) had the highest proportion of drug-resistant pulmonary TB. There was no statistically significant clustering, and the pattern of cases was primarily random. Most of the hotspots generated were present near the administrative boundaries of TUs, and the new ones mostly appeared in the area near the previous hotspots. A random pattern seen in cluster analysis supports the universal drug testing policy of India. Hotspot analysis helps cross administrative border initiatives with targeted active case finding and proper follow-up.

Weight Changes and its Determinants among Sputum Positive Pulmonary TB Patients in Bengaluru – A Prospective Study

Background and Objectives Underweight indicating undernutrition has a bidirectional relationship with Tuberculosis TB and is an established prognostic risk factor. It contributes to an estimated 55 of annual TB incidence in India. Positive weight changes among Indian patients without additional nutritional support are in the range of 3ndash4 kg. Undernourished patients with TB get into a vicious cycle of worsening disease and undernutrition which is detrimental. With this background we intend to assess the weight changes and its determinants among newly diagnosed drug sensitive smear positive pulmonary TB patients and estimate the prevalence of undernutrition.Methodology A prospective study was conducted among 121 newly diagnosed drug sensitive smear positive pulmonary TB patients ge 18 years registered in selected tuberculosis units in Bangalore. A pretested questionnaire was administered weight and height were measured at recruitment. Patients were followed up for weight assessment at the end of two and six months. Repeated ANOVA measures were applied to see statistical differences in the weight changes between the start of treatment end of two months and six months.Results Mean weight at the start of the treatment end of two months and six months was 55.72plusmn8.9 56.7plusmn8.5 and 58.2plusmn8.2 kg respectively. The weight changes between the groups was found to be statistically significant p value lt0.001. Mean weight gain in the study subjects was 2.3plusmn1.4 kg. An average of 4 positive weight change was seen at the end of the treatment. Positive weight change was significantly associated with higher socio economic status absence of alcohol consumption absence of tobacco use absence of clubbing and pallor in TB patients while only absence of pallor OR-16.169.3-3.7 and tobacco use OR-12.6 43.9-3.5 in multivariate analysis showed a p value lt 0.05.Conclusion Monitoring the weight regularly in TB patients during the course of treatment with proper nutritional counselling is essential for treatment support and success of National TB Elimination Program NTEP as the nutritional status has a bidirectional relationship with TB acting as an important determinant factor for treatment success

Altered Microbial Composition of Drug-Sensitive and Drug-Resistant TB Patients Compared with Healthy Volunteers.

Mycobacterium tuberculosis infection has three discernible outcomes: active tuberculosis, latent tuberculosis, or clearance of the bacterium. The outcome of the infection depends on the interaction of the bacterium, the immune system, and the microbiome of the host. The current study uses 16S rRNA sequencing to determine the diversity and composition of the respiratory microbiome of drug-resistant and drug-sensitive tuberculosis patients as well as healthy volunteers. Tuberculosis patients exhibited increased microbial diversity and differentially abundant bacteria than healthy volunteers. Compositional differences were also observed when comparing drug-sensitive or -resistant tuberculosis patients. Finally, we defined and assessed the differences in the core sputum microbiota between tuberculosis patients and healthy volunteers. Our observations collectively suggest that in sputum, Mycobacterium tuberculosis infection is related to altered bacterial diversity and compositional differences of core members of the microbiome, with potential implications for the bacterial pulmonary ecosystem’s stability and function.

Determinants of household catastrophic costs for drug sensitive tuberculosis patients in Kenya

BackgroundDespite free diagnosis and treatment for tuberculosis (TB), the costs during treatment impose a significant financial burden on patients and their households. The study sought to identify the determinants for catastrophic costs among patients with drug-sensitive TB (DSTB) and their households in Kenya.MethodsThe data was collected during the 2017 Kenya national patient cost survey from a nationally representative sample (n = 1071). Treatment related costs and productivity losses were estimated. Total costs exceeding 20% of household income were defined as catastrophic and used as the outcome. Multivariable Poisson regression analysis was performed to measure the association between selected individual, household and disease characteristics and occurrence of catastrophic costs. A deterministic sensitivity analysis was carried using different thresholds and the significant predictors were explored.ResultsThe proportion of catastrophic costs among DSTB patients was 27% (n = 294). Patients with catastrophic costs had higher median productivity losses, 39 h [interquartile range (IQR): 20–104], and total median costs of USD 567 (IQR: 299–1144). The incidence of catastrophic costs had a dose response with household expenditure. The poorest quintile was 6.2 times [95% confidence intervals (CI): 4.0–9.7] more likely to incur catastrophic costs compared to the richest. The prevalence of catastrophic costs decreased with increasing household expenditure quintiles (proportion of catastrophic costs: 59.7%, 32.9%, 23.6%, 15.9%, and 9.5%) from the lowest quintile (Q1) to the highest quintile (Q5). Other determinants included hospitalization: prevalence ratio (PR) = 2.8 (95% CI: 1.8–4.5) and delayed treatment: PR = 1.5 (95% CI: 1.3–1.7). Protective factors included receiving care at a public health facility: PR = 0.8 (95% CI: 0.6–1.0), and a higher body mass index (BMI): PR = 0.97 (95% CI: 0.96–0.98). Pre TB expenditure, hospitalization and BMI were significant predictors in all sensitivity analysis scenarios.ConclusionsThere are significant inequities in the occurrence of catastrophic costs. Social protection interventions in addition to existing medical and public health interventions are important to implement for patients most at risk of incurring catastrophic costs.Graphic abstract

Evaluation of adherence monitoring system using evriMED with a differentiated response compared to standard of care among drug-sensitive TB patients in three provinces in South Africa: a protocol for a cluster randomised control trial

BackgroundSouth Africa has achieved drug-susceptible TB (DS-TB) treatment success of only 77% among people with new and previously treated TB. Alternative approaches are required to improve medication adherence and treatment completion to limit transmission, TB relapse and the development of resistance. This study aims to implement and evaluate the use of adherence medication monitors (Wisepill evriMED 1000) with a differentiated response to patient care, among DS-TB patients in three provinces of South Africa.MethodsIn total, 18 public health clinics across three provinces were selected. Clinics were randomised to intervention or standard of care clinics. In each clinic, approximately 145 DS-TB patients are being enrolled to reach a total of 2610. All patients have their daily adherence monitored using medication monitors. In the intervention arm, patients are receiving medication monitor reminders and differentiated care in response to adherence data. This weekly review of daily real-time monitoring will be undertaken from a central database. The differentiated care model includes automated SMS reminders with a missed dose, research staff-initiated phone call to the patient with a second or third missed dose, a home visit if four or more doses are missed, and motivational counselling if four or more doses are missed repeatedly. Fidelity of the intervention will be measured through process evaluation. Patients in control clinics will receive medication monitors for adherence tracking, standard of care TB education, and normal clinic follow-up procedures. The primary outcome is the proportion of patients by arm with >80% adherence, as measured by the medication monitor. The feasibility and acceptability of the intervention will be assessed by in-depth interviews with patients, stakeholders, and study staff. A cost effectiveness analysis of the intervention and standard of care clinics will be conducted.SignificanceThis trial will provide evidence for the use of an intervention, including medication monitors and differentiated care package, to improve adherence to TB treatment. Improved adherence should also improve TB treatment completion rates, thus reducing loss to follow-up rates, and TB relapse among people with TB. The intervention is intended to ultimately improve overall TB control and reduce TB transmission in South Africa.Trial registrationPan African Trial Registry PACTR201902681157721. Registered on 11 February 2019.

Leukocytes from Patients with Drug-Sensitive and Multidrug-Resistant Tuberculosis Exhibit Distinctive Profiles of Chemokine Receptor Expression and Migration Capacity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains as a leading infectious cause of death worldwide. The increasing number of multidrug-resistant TB (MDR-TB) cases contributes to the poor control of the TB epidemic. Currently, little is known about the immunological requirements of protective responses against MDR-TB. This is of major relevance to identify immune markers for treatment monitoring and targets for adjuvant immunotherapies. Here, we hypothesized that MDR-TB patients display unique immunophenotypical features and immune cell migration dynamics compared to drug-sensitive TB (DS-TB). Hence, we prospectively conducted an extensive characterization of the immune profile of MDR-TB patients at different time points before and after pharmacological therapy. For this purpose, we focused on the leukocyte expression of chemokine receptors, distribution of different monocyte and lymphocyte subsets, plasma levels of chemotactic factors, and in vitro migration capacity of immune cells. Our comparative cohort consisted of DS-TB patients and healthy volunteer donors (HD). Our results demonstrate some unique features of leukocyte migration dynamics during MDR-TB. These include increased and prolonged circulation of CD3+ monocytes, CCR4+ monocytes, EM CD4+ T cells, EM/CM CD8+ T cells, and CXCR1+CXCR3+ T cells that is sustained even after the administration of anti-TB drugs. We also observed shared characteristics of both MDR-TB and DS-TB that include CCR2+ monocyte depletion in the blood; high plasma levels of MPC-1, CCL-7, and IP-10; and increased responsiveness of leukocytes to chemotactic signals in vitro. Our study contributes to a better understanding of the MDR-TB pathobiology and uncovers immunological readouts of treatment efficacy.

Knowledge about tuberculosis, treatment adherence and outcome among ambulatory patients with drug-sensitive tuberculosis in two directly-observed treatment centres in Southwest Nigeria

BackgroundTuberculosis (TB) remains one of the most common infectious diseases worldwide. Although TB is curable provided the treatment commenced quickly, appropriately and uninterrupted throughout TB treatment duration. However, high default rate, treatment interruption and therapy non-adherence coupled with inadequate disease knowledge significantly contribute to poor TB treatment outcome, especially in developing countries. This study therefore assessed knowledge about TB and possible reasons for treatment non-adherence among drug-sensitive TB (DS-TB) patients, as well as evaluated treatment outcomes for the DS-TB managed within a 5-year period.MethodsA mixed-method design comprising a cross-sectional questionnaire-guided survey among 140-ambulatory DS-TB patients from January–March 2019, and a retrospective review of medical-records of DS-TB managed from 2013 to 2017 in two WHO-certified TB directly-observed-treatment centres. Data were summarized using descriptive statistics, while categorical variables were evaluated with Chi-square at p < 0.05.ResultsAmong the prospective DS-TB patients, males were 77(55.0%) and females were 63(45.0%). Most (63;45.0%) belonged to ages 18-34 years. A substantial proportion knew that TB is curable (137;97.9%) and transmittable (128;91.4%), while 107(46.1%) accurately cited coughing without covering the mouth as a principal mode of transmission. Only 10(4.0%) mentioned adherence to TB medications as a measure to prevent transmission. Inaccessibility to healthcare facility (33;55.0%) and pill-burden (10,16.7%) were topmost reasons for TB treatment non-adherence. Of the 2262-DS-TB patients whose treatment outcomes were evaluated, 1211(53.5%) were cured, 580(25.6%) had treatment completed, 240(10.6%) defaulted, 54(2.3%) failed treatment and 177(7.8%) died. Overall, the treatment success rate within the 5-year period ranged from 77.4 to 81.9%.ConclusionsKnowledge about TB among the prospective DS-TB patients is relatively high, especially with respect to modes of TB transmission and preventive measures, but a sizeable number lacks the understanding of ensuring optimal TB medication-adherence to prevent TB transmission. Inaccessibility to healthcare facility largely accounts for treatment non-adherence. Outcomes of treatment within the 5-year period show that nearly half were cured, while almost one-tenth died. Overall treatment success rate is about 12% below the WHO-defined target. There is generally a need for concerned stakeholders to step-up efforts in ensuring consistent TB enlightenment, while improving access to TB care is essential for better treatment outcome.

Serum zinc level and its association with multidrug-resistant tuberculosis.

Zinc deficiency is evident in chronic diseases, but little is known about its association with multi-drug resistant tuberculosis (MDRTB). We aimed to measure serum zinc level in MDRTB patients and explore its association with MDRTB compared to drug-sensitive tuberculosis (DSTB). We recruited 107 MDRTB and 87 DSTB patients from a tuberculosis referral hospital in Bangladesh. After overnight fasting, 5 ml venous blood was collected from each patient to measure serum zinc level through graphite furnace atomic absorption spectrophotometry method. Multivariate logistic regression was done to measure its association with MDRTB. The mean age of all patients was 36 years, where 70% were male. About 27% MDRTB patients and 2.3% DSTB patients had low serum zinc level (P < 0.0001). An inverse correlation was observed between serum zinc level and duration of anti-TB therapy (r-value: -0.252, P < 0.01). Reduced serum zinc level (odds ratio, 0.957; 95% confidence interval 0.923-0.992) was found as a significant associating factor for MDRTB after adjusted with age, sex, occupation, residence, tobacco consumption, Bacillus Calmette-Guérin-vaccination, and duration of anti-TB therapy. A lower serum zinc level is significantly associated with MDRTB. The tuberculosis control program should address this in the MDRTB control strategy.

Determinants of drug resistant & drug sensitive tuberculosis patients from North India-a case control study

Background and objectiveThe burden of drug resistant tuberculosis (DRTB) has posed a huge challenge to for the governments, throughout the world. India has 27% of the global DRTB burden with incidence of 130,000 cases. India has kept an ambitious target of elimination of tuberculosis by 2025 which requires understanding and mitigating various determinants of DRTB. MethodsThe retrospective case control study was undertaken from May to September 2019 among drugresistant (cases) and drug sensitive (controls) tuberculosis patients from two districts of Himachal Pradesh, India. A total of 211 participants were recruited in the study, which includes all 102 cases and randomly selected, age and sex matched 109 controls. A semi structured questionnaire, adapted from a study by Lobo et al, was used for assessing the determinants of DRTB and DSTB. The data collection was undertaken from district and block level health care facilities followed by home visits to patients. Multivariate logistic regression was used to determine risk factors associated with DRTB. ResultsDiagnostic delay (aOR-7.72, p value 0.000), history of treatment default (aOR-2.97, self history of tuberculosis (aOR 1.42, p value 0.01), migration (aOR-4.84, p value 0.000), smoking (aOR-2.70, p value 0.014), and belonging to rural area (aOR-2.62, p value- 0.013) were found as independent risk factors for the occurrence of DRTB. ConclusionThe risk factors identified in the study should be prioritized by the policy makers, implementators and educators for framing appropriate policies in TB control programme in India. The diagnostic delay as a risk factor merits active case finding of TB patients and educating health care staff and community.

Predicting TB treatment outcomes using baseline risk and treatment response markers: developing the PredictTB early treatment completion criteria

Standard treatment of drug-sensitive pulmonary tuberculosis requires six months of treatment. Several randomized clinical trials have attempted to shorten treatment to four months using various strategies but thus far all have failed. The PredictTB trial is an ongoing international randomized clinical trial testing a treatment shortening strategy whereby only drug-sensitive pulmonary TB patients who meet the study early treatment completion criteria are randomized to four vs. six months of treatment. The PredictTB early treatment completion criteria were developed based on a cohort of 92 pulmonary tuberculosis patients treated programmatically through the local tuberculosis treatment program in Cape Town, South Africa, with FDG-PET/CT scans also performed at baseline and week 4 of treatment. Patients were followed for one year after the end of therapy for programmatic treatment outcomes. This methodology paper describes how the PET/CT scans and GeneXpert cycle threshold data of this cohort were analyzed to develop the early treatment completion algorithm currently being used in the PredictTB trial.

Households experiencing catastrophic costs due to tuberculosis in Uganda: magnitude and cost drivers

BackgroundTuberculosis (TB) patients in Uganda incur large costs related to the illness, and while seeking and receiving health care. Such costs create access and adherence barriers which affect health outcomes and increase transmission of disease. The study ascertained the proportion of Ugandan TB affected households incurring catastrophic costs and the main cost drivers.MethodsA cross-sectional survey with retrospective data collection and projections was conducted in 2017. A total of 1178 drug resistant (DR) TB (44) and drug sensitive (DS) TB patients (1134), 2 weeks into intensive or continuation phase of treatment were consecutively enrolled across 67 randomly selected TB treatment facilities.ResultsOf the 1178 respondents, 62.7% were male, 44.7% were aged 15–34 years and 55.5% were HIV positive. For each TB episode, patients on average incurred costs of USD 396 for a DS-TB episode and USD 3722 for a Multi drug resistant tuberculosis (MDR TB) episode. Up to 48.5% of households borrowed, used savings or sold assets to defray these costs. More than half (53.1%) of TB affected households experienced TB-related costs above 20% of their annual household expenditure, with the main cost drivers being non-medical expenditure such as travel, nutritional supplements and food.ConclusionDespite free health care in public health facilities, over half of Ugandan TB affected households experience catastrophic costs. Roll out of social protection interventions like TB assistance programs, insurance schemes, and enforcement of legislation related to social protection through multi-sectoral action plans with central NTP involvement would palliate these costs.