Tuberculosis Case Treatment Research Articles

Diagnostic accuracy of cartridge-based nucleic acid amplification test and resistance pattern in new and previously treated tuberculosis cases: A prospective observational study

Background: Diagnostic methods, particularly sputum microscopy, are the standard method for diagnosing tuberculosis (TB) in many settings. The emergence of cartridge-based nucleic acid amplification test (CBNAAT) as a newer diagnostic tool for TB has shown promising results. CBNAAT is a rapid molecular test that detects the genetic material of Mycobacterium tuberculosis (MTB), the bacterium causing TB, in sputum samples. It offers higher sensitivity and faster results compared to sputum microscopy. Aim: The study aimed to 1) compare the diagnostic accuracy of CBNAAT in detecting smear-positive and smear-negative pulmonary TB cases, and 2) compare rifampicin resistance prevalence between newly diagnosed and previously treated pulmonary TB patients. Methodology: A hospital-based prospective study was conducted in the Respiratory Medicine Department of Guru Gobind Singh Government Hospital, Jamnagar, on PTB patients from August 2019 to December 2020. Data were collected through a self-structured questionnaire that included detailed clinical history, radiological, biochemical, and microbiological investigations. Descriptive statistical analyses were performed to present data as percentages and frequencies. Diagnostic accuracy analysis was conducted. A P-value <0.05 was considered significant. Results: Out of 150 cases, 104 (69.3 %) were male, while 46 (30.7%) were female. Sixty-one percent of new and 86% of previously treated cases were male, whereas 39% of new and 14% of previously treated cases were female. The sensitivity of sputum smear microscopy is 77.33% in cases of PTB, whereas sputum CBNAAT detected 94% of cases of PTB. The sensitivity of CBNAAT for MTB detection in smear microscopy–positive samples was 93.97%, whereas the sensitivity in smear microscopy–negative samples was 94.12%. Regarding rifampicin resistance, the prevalence was lower in newly diagnosed (3/100) compared to previously treated patients with rifampicin-resistant PTB (3/50). Conclusion: These findings suggest that CBNAAT can be a valuable tool for the detection of TB, particularly in cases where sputum smear microscopy results are negative. However, further research is needed to validate these results and evaluate the clinical implications of using CBNAAT in routine TB diagnostics.

Enhanced active case finding of drug-resistant tuberculosis in Namibia: a protocol for the hotspots, hospitals, and households (H3TB) study

IntroductionNamibia is a high tuberculosis (TB)-burden country with an estimated incidence of 460/100 000 (around 12 000 cases) per year. Approximately 4.5% of new cases and 7.9% of previously treated...

Resistance to pyrazinamide in Mycobacterium tuberculosis complex isolates from previously treated tuberculosis cases in Southwestern Oromia, Ethiopia

ObjectivePyrazinamide (PZA) susceptibility testing is important to develop evidence-based algorithms for case management. We aimed to assess the prevalence of PZA-resistance and its impact on treatment outcomes in previously treated tuberculosis (TB) cases in southwestern Oromia, Ethiopia. MethodsA Phenotypic Drug Susceptibility Testing (DST) of PZA with BACTEC MGIT 960 was conducted at the Mycobacteriology Research Center of Jimma University (MRC-JU) from June to November 2021 on sixty-six Mycobacterium tuberculosis complex (MTBC) isolates from previously treated TB cases. SPSS software package version 21 was used. The differences in the proportion of PZA resistance between the groups were compared using the chi squared test. Logistic regression was used to identify the association between PZA resistance and treatment outcomes. ResultsAmong 66 MTBC isolates (49 rifampicin-resistant and 17 rifampicin-sensitive) included in this study, 31.8 % were resistant to PZA. The proportion of PZA resistance was almost three times higher in previously treated TB cases with rifampicin resistance than in rifampicin-sensitive patients (38.8 % vs. 11.8 %, p = 0.039). An unfavorable treatment outcome was documented for 23 % (15/65) of the participants. Patients with PZA resistance were almost four times more likely to have an unfavorable treatment outcome than patients with PZA sensitive (aOR 4.2, 95 % CI: 1.13–15.3). ConclusionsThe prevalence of PZA resistance was high compared to the pooled PZA resistance estimated worldwide. The majority of TB cases with PZA resistance had an unfavorable treatment outcome. PZA susceptibility testing should be included in the multidrug-resistant TB diagnostic algorithm to improve management of these patients.

A mathematical analysis of the two-strain tuberculosis model dynamics with exogenous re-infection

The rise of drug resistance has become a major obstacle in treating tuberculosis (TB), significantly contributing to the increasing disease burden. Therefore, it is essential to study the transmission dynamics of the disease, considering the factors that contribute to the strain’s impact on the disease burden, using an epidemiological model. We present a deterministic mathematical model that explores the dynamics of TB with two strains: drug-susceptible and drug-resistant, taking into account exogenous re-infection. We thoroughly analyze to gain insights into the behavior of the model. The qualitative analysis of the model reveals an interesting phenomenon known as “backward bifurcation,” where both stable disease-free and stable endemic equilibria coexist when the associated reproduction number is less than one. In the absence of exogenous re-infection, the model shows the existence of unique positive endemic equilibria. Numerical simulations were conducted, yielding noteworthy results. Increasing the treatment rate for individuals infected with the drug-susceptible strain reduces the number of new cases of drug-susceptible TB while increasing the detection of drug-resistant TB cases. The simulations demonstrate that drug-susceptible and drug-resistant TB strains can coexist when their reproduction numbers exceed one without competitive exclusion occurring. In summary, this study sheds light on the challenges posed by drug resistance in TB treatment and highlights the importance of understanding the disease dynamics through mathematical modeling to develop effective strategies for its control.

Association Between Cycle Threshold Value of Cartridge-Based Nucleic Acid Amplification Test and Clinical Severity of Pulmonary Tuberculosis: A Cross-sectional Study

Introduction: Tuberculosis (TB) is a major global health problem caused by Mycobacterium tuberculosis (MTB). The National Tuberculosis Elimination Programme (NTEP) emphasises early diagnosis and treatment of TB cases. The Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) is a semi-automated molecular assay that rapidly detects MTB Deoxyribonucleic Acid (DNA) and Rifampicin (RIF) resistance-associated mutations using Real-Time Polymerase Chain Reaction (RT-PCR). Aim: This cross-sectional study aims to assess the association between the Cycle Threshold (Ct) value of CBNAAT and the clinical severity of Pulmonary Tuberculosis (PTB). Materials and Methods: The study was conducted at the Department of Respiratory Medicine, Navodaya Medical College Hospital and Research Centre-Raichur, from January 2020 to July 2021. A sample size of 106 participants, aged ≥18 years and meeting the NTEP guidelines for presumptive PTB cases, were enrolled. Participants underwent chest radiography, sputum smear microscopy for Acid-Fast Bacilli (AFB), and CBNAAT testing. Clinical severity of PTB was categorised as mild, moderate, or severe using the Bandim TB score. Data was entered into Microsoft Excel 2017, and statistical analysis was performed using SPSS version 23. Descriptive statistics, frequencies, percentages, means, and standard deviations were calculated, and the chi-square test was utilised to assess associations between qualitative variables. Results: Among the participants, the majority (55.7%, n=59) had moderate clinical severity. Of these, 12.3% (n=13) had high CBNAAT Ct values, 20.8% (n=22) had medium Ct values, 11.3% (n=12) had low Ct values, and 11.3% (n=12) had very low Ct values. A total of 31.1% (n=33) had severe clinical severity, with 13.2% (n=6) having high Ct values, 12.3% (n=13) having medium Ct values, and 6.6% (n=7) each having low and very low Ct values. Additionally, 13.2% (n=14) had mild clinical severity, with 0.9% (n=1) having high Ct values, 3.8% (n=4) having medium Ct values, 5.7% (n=6) having low Ct values, and 2.8% (n=3) having very low Ct values. The chi-square value was 4.697, with a p-value of 0.58. Conclusion: There is no association between the Ct value of CBNAAT and the clinical severity of PTB.

Pre-extensively drug-resistant tuberculosis among pulmonary multidrug-resistant tuberculosis patients in Eastern Nigeria.

Pre-extensively drug-resistant tuberculosis (Pre-XDR-TB), an emerging form of drug-resistant tuberculosis, is challenging efforts at tuberculosis control, leading to treatment failure among multidrug-resistant tuberculosis (MDR-TB) patients and progression to extensively drug-resistant tuberculosis (XDR-TB). We determined the rate of Pre-XDR-TB among multidrug-resistant patients in Southeast, Nigeria. A prospective laboratory-based study was carried out at the South East Zonal Tuberculosis Reference Laboratory from January 2021 to December 2021. Second-line drug (SLD) resistance was performed on 225 sputum samples of multidrug-resistant patients prior to treatment initiation using GenoType MTBDRsl genotypic drug susceptibility testing (DST) method. The rate of Pre-XDR-TB among 225 MDR-TB cases was 3.1%. Fluoroquinolone-resistant Pre-XDR-TB was observed (100%) in previously treated tuberculosis cases. Only one (0.4%) case showed resistance to both fluoroquinolone (FQ) and one second-line injectable drug (XDR-TB). The extensively drug-resistant case observed was a de-novo resistance. Exactly 0.9% of the multidrug-resistant cases showed resistance to second-line injectables. The prevalence of Pre-XDR-TB among MDR-TB cases was high. There is need for rapid detection of Pre-XDR-TB among MDR-TB cases before treatment initiation.

Incidence of tuberculosis among PLHIV on antiretroviral therapy who initiated isoniazid preventive therapy: A multi-center retrospective cohort study.

Isoniazid preventive therapy (IPT) is effective in treating tuberculosis (TB) infection and hence limiting progression to active disease. However, the durability of protection, associated factors and cost-effectiveness of IPT remain uncertain in low-and-middle income countries, Uganda inclusive. The Uganda Ministry of health recommends a single standard-dose IPT course for eligible people living with HIV (PLHIV). In this study we determined the incidence, associated factors and median time to TB diagnosis among PLHIV on Antiretroviral therapy (ART) who initiated IPT. We conducted a retrospective cohort study at eleven The AIDS Support Organization (TASO) centers in Uganda. We reviewed medical records of 2634 PLHIV on ART who initiated IPT from 1st January 2016 to 30th June 2018, with 30th June 2021 as end of follow up date. We analyzed study data using STATA v.16. Incidence rate was computed as the number of new TB cases divided by the total person months. A Frailty model was used to determine factors associated with TB incidence. The 2634 individuals were observed for 116,360.7 person months. IPT completion rate was 92.8%. Cumulative proportion of patients who developed TB in this cohort was 0.83% (22/2634), an incidence rate of 18.9 per 100,000 person months. The median time to TB diagnosis was 18.5 months (minimum- 0.47; maximum- 47.3, IQR: 10.1-32.4). World Health Organization (WHO) HIV clinical stage III (adjusted hazard ratio (aHR) 95%CI: 3.66 (1.08, 12.42) (P = 0.037) and discontinuing IPT (aHR 95%CI: 25.96(4.12, 169.48) (p = 0.001)), were associated with higher odds of TB diagnosis compared with WHO clinical stage II and IPT completion respectively. Incidence rates of TB were low overtime after one course of IPT, and this was mainly attributed to high completion rates.

Costs and cost-effectiveness of Gene Xpert compared to smear microscopy for the diagnosis of pulmonary tuberculosis using real-world data from Arsi zone, Ethiopia.

BackgroundEarly diagnosis and treatment are one of the key strategies of tuberculosis control globally, and there are strong efforts in detecting and treating tuberculosis cases in Ethiopia. Smear microscopy examination has been a routine diagnostic test for pulmonary tuberculosis diagnosis in resource-constrained settings for decades. Recently, many countries, including Ethiopia, are scaling up the use of Gene Xpert without the evaluation of the cost and cost-effectiveness implications of this strategy. Therefore, this study evaluated the cost and cost-effectiveness of Gene Xpert (MTB/RIF) and smear microscopy tests to diagnosis tuberculosis patients in Ethiopia.MethodsWe compared the costs and cost-effectiveness of tuberculosis diagnosis using smear microscopy and Gene Xpert among 1332 patients per intervention in the Arsi zone. We applied combinations of top-down and bottom-up costing approaches. The costs were estimated from the health providers’ perspective within one year (2017–2018). We employed “cases detected” as an effectiveness measure, and the incremental cost-effectiveness ratio was calculated by dividing the changes in cost and change in effectiveness. All costs and incremental cost-effectiveness ratio were reported in 2018 US$.ResultsThe unit cost per test for Gene Xpert was $12.9 whereas it is $3.1 for AFB smear microscopy testing. The cost per TB case detected was $77.9 for Gene Xpert while it was $55.8 for the smear microscopy method. The cartridge kit cost accounted for 42% of the overall Gene Xpert’s costs and the cost of the reagents and consumables accounted for 41.3% ($1.3) of the unit cost for the smear microscopy method. The ICER for the Gene Xpert strategy was $20.0 per tuberculosis case detected.ConclusionUsing Gene Xpert as a routine test instead of standard care (smear microscopy) can be potentially cost-effective. In the cost scenario analysis, the price of the cartridge, the number of tests performed per day, and the life span of the capital equipment were the drivers of the unit cost of the Gene Xpert method. Therefore, Gene Xpert can be a part of the routine TB diagnostic testing strategy in Ethiopia.

The effect of empirical and laboratory-confirmed tuberculosis\xa0on treatment outcomes

The World Health Organization (WHO) criteria for diagnosing and treating Tuberculosis (TB) includes clinical signs, therefore not requiring bacteriological laboratory confirmation. In resource-limited settings, including Kenya, this empirical TB treatment is routine practice however limited data exist on patient clinical outcomes when comparing the method of diagnosis. We evaluated TB treatment outcomes comparing clinically diagnosed and bacteriologically confirmed TB, 6 months after starting treatment of TB in a rural county in Kenya. Our analysis compared patients with a clinical versus a bacteriologically confirmed TB diagnosis. In this retrospective analysis, we included all adults (≥ 18 years) starting treatment of TB and followed up for 6 months, within the County TB surveillance database from 2012 to 2018. Patients included from both public and private facilities. The TB treatment outcomes assessed included treatment success, treatment failure, death, defaulted and transferred out. We used survival regression models to assess effect of type of diagnosis on TB treatment outcome defining time at risk from date of starting treatment to experiencing one of the treatment outcomes or completing 6-months of treatment. A total of 12,856 patients; median age 37 [IQR 28 − 50] years were included. 7639 (59%) were male while 11,339 (88%) were pulmonary TB cases. Overall, 11,633 (90%) were given first-line TB treatment and 3791 (29%) were HIV infected. 6472 (50%) of the patients were clinically diagnosed of whom 4521/6472 (70%) had a negative sputum/GeneXpert test. During the study 5565 person-years (PYs) observed, treatment success was 82% and 83% amongst clinically and bacteriologically diagnosed patients (P = 0.05). There were no significant differences in defaulting (P = 0.70) or transfer out (P = 0.19) between clinically and bacteriologically diagnosed patients. Mortality was significantly higher among clinically diagnosed patients: 639 (9.9%) deaths compared to 285 (4.5%) amongst the bacteriologically diagnosed patients; aHR 5.16 (95%CI 2.17 − 12.3) P < 0.001. Our study suggests survival during empirical TB treatment is significantly lower compared to patients with laboratory evidence, irrespective of HIV status and age. To improve TB treatment outcomes amongst clinically diagnosed patients, we recommend systematic screening for comorbidities, prompt diagnosis and management of other infections.

Molecular Detection of Drug-Resistant Mycobacterium tuberculosis in Sputum Specimens from the New and Previously Treated Tuberculosis Cases at the National Reference Chest Diseases Laboratory in Lusaka, Zambia

Background: Drug-Resistant Tuberculosis (DR-TB) is one of the major public health issues globally. Zambia is highly burdened by TB and multi-drug resistant TB. In this study, sputum samples obtained from the new and previously treated cases of TB were examined for drug-resistant Mycobacterium tuberculosis (MTB). Methods: Sputum specimens were processed using the N-acetyl-L-cysteine-sodium hydroxide method, stained and examined using fluorescent technique and microscopy respectively. Mycobacterial DNA was extracted using the Genolyse kit, then subjected to multiplex polymerase chain reaction amplification and reverse hybridization. Drug-resistance and mutations in MTB genes were detected using the Genotype MTBDRplus VER 2.0 and MTBDRsl VER 2.0 assays. Results: A total of 329 MTB-positive sputum specimens, 102 from the new TB cases and 227 from previously treated TB cases, were analysed for drug-resistance. Among the new TB cases, 3.9% had Rifampicin (RIF) mono-resistance, 12.8% Isoniazid (INH) mono-resistance, and 17.7% had Multi-Drug Resistance (MDR). For the previously treated TB cases, 10.1% had RIF mono-resistance, 6.6% INH mono-resistance, 33.0% MDR, 1.8% poly-drug resistance, and 0.8% had pre-Extensively Drug-Resistance (pre-XDR). Mutations identified were rpoB (Ser531Leu, His526Asp, Asp516Val, His526Tyr, and Glu510His), katG (Ser315Thr 1 and Ser315Thr 2), InhA (Cys15Thr), gyrA (Ala90Val and Asp94Gly), and eis (Cys14Thr), each with a varying frequency. Conclusion: DR-TB is prevalent, especially MDR-TB, which is currently the most worrisome form of DR-TB and an emerging threat hampering efforts in the control of TB in Zambia. The early detection and effective treatment of TB cases are key in the control of DR-TB.

Prevalence and associated risk factors of drug-resistant tuberculosis in Thailand: results from the fifth national anti-tuberculosis drug resistance survey.

To assess the prevalence and risk factors of drug-resistant tuberculosis (TB), the fifth national anti-TB drug resistance survey was conducted in Thailand. A cross-sectional study was conducted by stratified cluster sampling with probability proportional to size of TB cases from public health facilities in 100 clusters throughout Thailand from August 2017 to August 2018. Susceptibility testing of TB isolates to first- and second-line anti-TB drugs was performed on Löwenstein-Jensen medium using the indirect proportion method. Multiple imputation was done for handling missing data using Stata 16. The proportion of TB cases with drug resistance was determined. The odds ratio was used to evaluate risk factors associated with drug-resistant TB. Among 1501 new TB and 69 previously treated TB cases, 14.0% [95% confidence interval (CI): 12.1-16.1] and 33.4% (95% CI: 23.6-44.8), respectively, had resistance to any anti-TB drug. Multidrug-resistant TB accounted for 0.8% (95% CI: 0.5-1.4) of new TB cases and 13.0% (95% CI: 6.5-24.4) of previously treated TB cases. Drug-resistant TB was associated with prior TB treatment [odds ratio (OR), 2.9; 95% CI: 1.6-5.0], age at 45-54years (OR, 1.6; 95% CI: 1.0-2.4), male (OR, 1.5; 95% CI: 1.0-2.1) and human immunodeficiency virus (HIV) infection (OR, 1.6; 95% CI: 1.0-2.4). The burden of drug-resistant TB remains high in Thailand. Intensified prevention and control measures should be implemented to reduce the risks of drug-resistant TB in high-risk groups previously treated, especially individuals of late middle age, males and those with coinfection of TB and HIV.

A Cbnaat based Study on Rifampicin Resistance in Tuberculosis in East Godavari District

Background: Globally 1.2 million Tuberculosis deaths occurred among HIV negative people and an estimated 251000 deaths occurred among HIV positive people in 2018. TB continues to be a public health threat as about half a million news cases were Rifampcin resistant. CBNAAT offer the prospect of very high sensitivity approaching that of liquid culture for TB diagnosis. It also provides information on drug susceptibility to rifampicin, which is a surrogate marker for identification of MDR TB cases. Objectives- 1.To know the magnitude of rifampicin resistance among TB cases. 2. To find out the incidence of TB HIV co-infection. Materials &amp; Method: Monthly Data regarding CBNAAT results during the year 2019 January-December was collected from District Tuberculosis Center (DTC), East Godavari district. Statistical analysis used: Data was entered and analyzed in MS-EXCEL. Results: A total of 20364 cases were screened for tuberculosis using CBNAAT, out of which 9366 patients were PLHIV (people living with HIV/AIDS). Among all the patients who were screened, 1951(9.6%) were positive for mycobacterium tuberculosis. 93(0.45%) cases were resistant to rifampicin. Among the PLHIV patients, 241(2.6%) were positive for tuberculosis. In those PLHIV cases, 20(0.2%) were resistant to rifampicin suggesting that rifampicin resistance was more common in HIV/AIDS. Among previously treated tuberculosis cases prevalence of rifampicin resistance was 5.1% as compared to 1.5% &amp; 1.8% among newly diagnosed cases &amp; non-responders respectively. Conclusion: CBNAAT is an effective tool in the diagnosis of tuberculosis and in identifying drug resistant tuberculosis. In our study drug resistance to rifampicin was more common in PLHIV and also in previously treated tuberculosis patients. By increasing the case detection rate of RR TB and TB-HIV co-infection cases using CBNAAT as the first line of diagnostic procedure we can be able to treat cases effectively in order to achieve the Sustainable Developmental Goal(SDG) of ending TB by 2025 as committed by Government of India

Prevalence of and risk factors associated with latent tuberculosis infection in a Latin American region

Tuberculosis (TB) represents a health problem in Colombia, and its control is focused on the search for contacts and treatment of TB cases underscoring the role of latent tuberculosis infection (LTBI) as a reservoir of Mycobacterium tuberculosis. The burden of LTBI in Colombia is unknown. We aimed to estimate the prevalence of LTBI and identify the associated risk factors. In this cross-sectional study, we recruited participants from four health care centers in Cali, Colombia. The participants were eligible if they were aged between 14 and 70 years, and all participants answered a survey evaluating their medical history and sociodemographic and lifestyle factors. LTBI status was based on tuberculin skin test (TST) positivity using two thresholds: ≥10 mm (TST-10) and ≥15 mm (TST-15). The magnitude of the associations between independent factors and dependent outcomes (LTBI status and TST induration) were evaluated by logistic regression and generalized linear models, respectively. A total of 589 individuals were included with TST positivity rates of 25.3% (TST-10) and 13.2% (TST-15). Logistic regression showed that being between age 40 and 69 years (OR = 7.28, 95% CI [1.62–32.7]), being male (OR = 1.71, 95% CI [1.04–2.84]), being employed (OR = 1.56, 95% CI [1.02–2.38]), and having a low intake of alcohol (OR = 2.40, 95% CI [1.13–5.11]) were risk factors for TST positivity, while living in the north zone (OR = 0.32, 95% CI [0.18–0.55]), living in the suburb zone (OR = 0.28, 95% CI [0.15–0.52]) and having a secondary education (OR = 0.49 95% CI [0.29–0.83]) lowered the risk of TST positivity. The generalized linear model showed that the previous predictors, as well as a low body mass index, had an effect on TST reaction size. The LTBI prevalence found in the population was moderate, reflecting the continuous transmission of M. tuberculosis. Social factors seem to play a decisive role in the risk of LTBI. Employed males, who are over 40 years of age, are overweight, have a lower level of education and have a low intake of alcohol (50–100 mL, once/week) should be a priority group for prophylactic treatment as a strategy for TB control in this city.

Video-observed therapy and medication adherence for tuberculosis patients: randomised controlled trial in Moldova.

The effectiveness of video-observed therapy (VOT) for treating tuberculosis (TB) has not been measured in low- and middle-income countries (LMICs), where >95% of TB cases and deaths occur. In this study, we analyse the effectiveness and patient cost-difference of VOT compared to clinic-based directly observed therapy (DOT) in improving medication adherence in Moldova, a LMIC in Eastern Europe. The study was a two-arm individually randomised trial with 197 TB patients (n=99 DOT control group; n=98 VOT treatment group; multidrug-resistant TB cases were excluded). The primary outcome was observed medication adherence, measured by the number of days that a patient failed to be observed adhering to medication for every 2-week period during the course of their treatment. VOT significantly decreased nonadherence by 4 days (95% CI 3.35-4.67 days, p<0.01) per 2-week period: 5.24 days missed per 2-week period for DOT and 1.29 days for VOT. VOT patients spent MDL 504 (∼EUR 25) (95% CI MDL 277-730, p<0.01) and 58 h (95% CI 48-68 h, p<0.01) less on their treatment. In addition, VOT increased self-reported satisfaction with treatment. We found no significant results pertaining to treatment success, patient wellbeing or patient employment status and some evidence of an increase in side-effects. In this trial, VOT increased observed medication adherence for TB patients in Moldova, a LMIC, when compared to clinic-based DOT. Additionally, VOT significantly reduced the time and money patients spent on their treatment.

A model-based investigation into urban-rural disparities in tuberculosis treatment outcomes under the Revised National Tuberculosis Control Programme in India.

In this study, we investigate differences in tuberculosis (TB) treatment outcomes between urban and rural India and estimate their impact on epidemiological outcomes such as TB incidence, prevalence and mortality using a mathematical model of TB transmission dynamics. Publicly available district-level treatment outcomes data for new and previously treated TB cases was analyzed in conjunction with census data providing the proportion of urban population in each district to determine the effect of urbanity/rurality on treatment outcomes. Districts were grouped in clusters based on the proportion of urban population in each district, wherein the clusters were identified by applying machine learning methods. Regression analyses revealed that average treatment success rates among both new and previously treated cases decline with increase in the proportion of urban population in a district cluster, with substantially sharper declines in treatment success rates with degree of urbanity observed for previously treated cases. The impact of differences in treatment outcomes on epidemiological outcomes was estimated using a dynamic transmission model developed for this purpose. For example, the cluster with highest treatment success rates is projected to have an average of 3.2% fewer deaths per 100,000 population in comparison with the national average across 2019–24, and the cluster with the lowest treatment success rates has an average of 4.5% more deaths per 100,000 in comparison with the national average. We anticipate that these disparities in TB treatment outcomes and epidemiology between urban and rural India may motivate investigations into the associated causes and their redressal.

The Effect of Treatment during A Haze/Post-Haze Year on Subsequent Respiratory Morbidity Status among Successful Treatment Tuberculosis Cases.

The purpose of this study was to evaluate the respiratory morbidity status within the two to three years among successful (completed/cured) treatment of tuberculosis cases during a haze year (2015) and a post-haze year (2016). The study was conducted among 133 cases of a 2015 group and 103 cases of a 2016 group between January to March 2018 in Pekanbaru city, Indonesia. The St George Respiratory Questionnaire (SGRQ) was used to assess respiratory morbidity status. A higher score corresponds to worse respiratory morbidity. Based on a directed acyclic graph, quantile regression models were constructed to assess the associations between haze/post-haze year and the SGRQ (symptom, activity, impact, and total) domains score. The subsequent respiratory morbidity status of tuberculosis (TB) cases was poorer among respondents treated during a haze year (2015). Among SGRQ domains, only the activity domain score showed significant difference, in which the median for the 2015 group was 23.7 (inter-quartile range (IQR); 17.2, 30.9) compared to 18.4 (IQR; 11.9, 24.8) for the 2016 group. The effect was limited to the 2015 group who were exposed by an average PM10 index ≥ 55 during TB treatment. This raises concern for monitoring and improving the quality of life of TB patients treated during a haze year.

Patient and health care system characteristics are associated with delayed treatment of tuberculosis cases in Taiwan

BackgroundThe decline of the incidence rate of tuberculosis in Taiwan has been partly attributed to the launch of the directly observed therapy short course (DOTS) program in 2006, followed by the DOTS-Plus in 2007. However, with the phasing out of the specialized tuberculosis care system and the declining incidence, clinical workers in Taiwan might become less familiar with the presentation of tuberculosis. Complementing the patient-pathway analysis with health system delay estimates, the objective of this study is twofold: to estimate the alignment between patient care initiation and the availability of prompt diagnostic and treatment services, and to identify the risk factors of delayed tuberculosis treatment.MethodsThe study population included all Taiwanese patients with incident tuberculosis in 2013. We (1) identified 11,507 incident tuberculosis patients from the 2013 National TB Registry, and (2) linked 10,932 Taiwanese from the registry to the 2012–2013 National Health Insurance Research Database. We assessed patient’s care-seeking pathways and associated the determinants of health system delay in a Cox model.ResultsThe overall health system delay was 46 days. We found that 20.5 and 3.5% of 10,932 tuberculosis patients were diagnosed and treated respectively at the initial visit to seek care for TB-related symptoms. Risk factors related to the prolonged health system delay included female gender (adjusted HR = 0.921, 95% CI: 0.884, 0.960), age > =65 years (adjusted HR = 0.720, 95% CI: 0.692, 0.750), non-severe (chest X-ray without cavities) (adjusted HR =0.721, 95% CI 0.683–0.760), chronic respiratory diseases (adjusted HR = 0.544, 95% CI: 0.522, 0.566), living in long-term care facilities (adjusted HR = 0.580, 95% CI: 0.525,0.640), an initial visit at a primary care clinic (adjusted HR = 0.588, 95% CI: 0.565, 0.612), and living in southern Taiwan (adjusted HR = 0.887, 95% CI: 0.798, 0.987).ConclusionsThe low access to TB diagnostic and treatment services at the initial visit and the prolonged health system delay indicate inefficiency in the health care system. Strengthening training of physicians at public hospitals and health workers at nursing homes might improve the efficiency and timeliness of tuberculosis diagnosis and treatment in Taiwan.

Notification of relapse and other previously treated tuberculosis in the 52 health districts of South Africa.

OBJECTIVE: To investigate the extent to which relapse and other previously treated tuberculosis (TB) contribute to the notified TB burden in South Africa.DESIGN: We conducted an ecological analysis at the level of the 52 South African health districts using national electronic TB register data. We included all bacteriologically confirmed TB cases treated for presumed drug-susceptible TB in 2011. Treatment history information was based on recorded patient categories (new vs. retreatment).RESULTS: Relapse and other previously treated TB cases constituted between 7.6% and 40% (median 17%, interquartile range 12-22) of all bacteriologically confirmed TB cases in the 52 South African districts. Multivariable analysis suggested that districts with higher proportions of previously treated TB cases had higher TB case notification rates (P < 0.001), lower estimates of antenatal human immunodeficiency virus (HIV) prevalence in the district population (P < 0.001) as well as lower HIV co-infection rates (P < 0.001) among new TB cases.CONCLUSION: Relapse and other previously treated TB cases contributed substantially to the notified TB burden in several South African health districts, particularly those with high case notification rates and lower antenatal HIV prevalence. Additional efforts to prevent TB among previously treated people, such as strengthening treatment monitoring and/or secondary preventive therapy, should be considered.

Assessment of lung function in successfully treated tuberculosis reveals high burden of ventilatory defects and COPD.

BackgroundBurden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear.MethodsWe performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC<LLN among participants with obstruction. Restrictive spirometry pattern was defined as FVC<LLN among participants without obstruction. Multivariable logistic and linear regression was used to identify risk-factors for obstruction, restriction and low lung function despite successful treatment.ResultsOf the 172 participants included in the analysis, 82 (48%) were female, 22 (13%) had diabetes and 34 (20%) ever-smoked with a median (IQR) exposure of 3.5 (0.2–9.9) pack-years. Median (IQR) age and body-mass index (BMI) at enrollment was 32 (23–39) years and 18.1 (16.0–20.5) kg/m2 respectively. Airflow obstruction was detected in 42 (24%) participants; of whom 9 (21%) responded to short-acting bronchodilators and 25 (56%) had COPD; and was associated with duration of illness prior to treatment (aOR = 1.32 per 30-days, 95%CI 1.04–1.68, p = 0.02). A restrictive spirometry pattern was detected in 89 (52%) participants and was associated with female sex (aOR = 3.73, 95%CI 1.51–9.17, p = 0.004) and diabetes (aOR = 4.06, 95%CI 1.14–14.42, p = 0.03). Higher HbA1c at treatment initiation was associated with greater odds of a restrictive spirometry pattern (aOR = 1.29 per unit higher HbA1c, 95%CI 1.04 to 1.60, p = 0.02).ConclusionWe found a high burden of lung function defects and COPD in tuberculosis cases who successfully completed treatment. Screening for chronic lung diseases following treatment and linkage to respiratory health clinics should be included in the routine management plan of all tuberculosis cases in India, regardless of conventional COPD risk-factors such as older age and smoking.

Global Epidemiology of Tuberculosis and Progress Toward Achieving Global Targets - 2017.

Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1) and the leading cause of death among persons living with human immunodeficiency virus (HIV) infection, accounting for approximately 40% of deaths in this population (2). The United Nations' (UN) Sustainable Development Goals (3) and the World Health Organization's (WHO's) End TB Strategy (4) have defined ambitious targets for 2020-2035, including a 35% reduction in the absolute number of TB deaths and a 20% reduction in TB incidence by 2020, compared with 2015 (4). Since 2000, WHO has produced annual TB estimates for all countries (1). Global and regional disease estimates were evaluated for 2017 to determine progress toward meeting targets. In 2017, an estimated 10 million incident cases of TB and 1.57 million TB deaths occurred, representing 1.8% and 3.9% declines, respectively, from 2016. Numbers of TB cases and disease incidence were highest in the WHO South-East Asia and Africa regions, and 9% of cases occurred among persons with HIV infection. Rifampicin-resistant (RR) or multidrug-resistant (MDR) (resistance to at least both isoniazid and rifampicin) TB occurred among 3.6% and 18% of new and previously treated TB cases, respectively (5.6% among all cases). Overall progress in global TB elimination was modest in 2017, consistent with that in recent years (1); intensified efforts to improve TB diagnosis, treatment, and prevention are required to meet global targets for 2020-2035.