Drug-susceptible Tuberculosis Research Articles

Routine tuberculosis contact investigation yield and preventive treatment cascade in central Ethiopia

IntroductionThere is a global gap between tuberculosis incident cases and the notified cases. Active household contact investigation is one of the strategies to narrow this gap. It has the advantage of giving early diagnosis and preventive treatment to vulnerable and eligible groups. This study assessed the practice of contact investigation and tuberculosis preventive treatment adherence in central Ethiopia. MethodA cross-sectional study covering all registered bacteriologically confirmed pulmonary tuberculosis patients and their close contacts was conducted in central Ethiopia from January 1, 2022, to December 30, 2022. ResultA total of 1372 household contacts were declared by the index cases. From these 79.44 % (1090) contacts received a one-time tuberculosis screening giving a total of four (0.36 %) active TB cases. Among 484 household contacts of drug-resistant tuberculosis index cases, 5.53 % (14) had presumptive tuberculosis and 0.79 % (2) had active tuberculosis. While among 837 household contacts of drug-susceptible tuberculosis index cases presumptive TB cases were 1.91 % (16) and active TB cases were 0.23 % (2). Of the 142 eligible under 15 children 81.69 % (116) had started tuberculosis preventive treatment and 84.48 % (98) completed the treatment. On multivariable logistic regression, the associated factor for tuberculosis preventive treatment non-adherence was age 2–5 years (aOR, 0.02, 95 % CI (0.002–0.20) and age 5–15 years (aOR, 0.04,95 % CI (0.002–0 0.95)) P=<0.05). ConclusionThere was low contact screening practice in the DR-TB index cases as compared to national and global targets. The yield of routine contact investigation was low and it indicates the quality of screening. Tuberculosis preventive treatment initiation and completion rates were also low as compared to those of many other countries and global achievements which need further improvement, especially for completion. Alternative mechanisms should be planned to increase the yield of tuberculosis screening and tuberculosis preventive treatment adherence.

Catastrophic costs for tuberculosis patients in India: Impact of methodological choices.

As financial risk protection is one of the goals towards universal health coverage, detailed information on costs, catastrophic costs and other economic consequences related to any disease are required for designing social protection measures. End Tuberculosis (TB) Strategy set a milestone of achieving zero catastrophic cost by 2020. However, a recent literature review noted that 7%-32% TB affected households in India faced catastrophic cost. Studies included in the review were small scale cross-sectional. We followed a cohort of 1482 notified drug-susceptible TB patients from four states in India: Assam, Maharashtra, Tamil Nadu, and West Bengal to provide a comprehensive picture of economic burden associated with TB treatment. Treatment cost was calculated using World Health Organization guidelines on TB patient cost survey and both human capital and output approaches of indirect cost (time, productivity, and income loss related to an episode) calculation were used to provide the range of households currently facing catastrophic cost. Depending on choice of indirect cost calculation method, 30%-61% study participants faced catastrophic cost. For over half of them, costs became catastrophic even before starting TB treatment as there was average 7-9 weeks delay from symptom onset to treatment initiation which was double the generally accepted delay of 4 weeks. During that period, they made average 8-11 visits to different providers and spent money on consultations, drugs, tests, and travel. Following the largest cohort of drug-susceptible TB patients till date, the study concluded that a significant proportion of study participants faced catastrophic cost and the proportion was much higher when income loss was considered as indirect cost calculation method. Therefore, ensuring uninterrupted livelihood during TB treatment is an absolute necessity. Another reason of high cost was the delay in diagnosis and costs incurred during pre-diagnosis period. This delay and consequently, economic burden, can be reduced by both supply side (intense private sector engagement, rapid diagnosis) and demand side (community engagement) initiatives. Reimbursement of expenses incurred before treatment initiation could be used as short-term measure for mitigating financial hardship.

Incidence, Outcomes, and Risk Factors for Isoniazid-Resistant Tuberculosis from 2012 to 2022 in Eastern China.

Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. Between January 2012 and December 2022, all Hr-TB patients' information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients' clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment.

Factors Associated with Successful Drug Susceptible Tuberculosis Treatment among Tuberculosis – Human Immunodeficiency Virus Patients in DKI Jakarta Province 2020 – 2022

Factors Associated with Successful Drug Susceptible Tuberculosis Treatment among Tuberculosis – Human Immunodeficiency Virus Patients in DKI Jakarta Province 2020 – 2022

Caregivers' experiences and practices for malnourished children undergoing tuberculosis treatment in Eswatini.

Eswatini is one of the countries affected by malnutrition and tuberculosis (TB) and some cases remained untreated. These two conditions are major public health problems. This study aimed to explore and describe caregivers' experiences and practices of children's nutrition during treatment. Baylor College of Nursing Children's Foundation - Eswatini (BCMCF-SD). A qualitative study following a narrative design used purposive sampling to identify 12 caregivers of malnourished children and informed consent obtained. In-depth interview used semi-structured interview guide and digital voice recorder. Field notes were taken, transcribed, translated and analysed using NVivo version 11. Two themes emerged as home's nutritional situation and health facility's nutritional support. The study found that most of the caregivers gave children unbalanced diet, while those less than a year were mixed-fed. Some caregivers reported experience of lost breadwinners, unemployment and high number of children than what the family could afford. The caregivers' practices around food by prescription included inadequate supply of the ready-to-use therapeutic food and sharing of prescribed food supplies with other healthy children. During treatment, children's caregivers need short health education and support. The Ministry of Health in Eswatini should consider using some comic books to guide that. Moreover, upscale vocational training promotes entrepreneurship and agricultural activities. Association of malnutrition and TB outcomes has provided evidence-based information for more comprehensive integration between nutrition programmes and tuberculosis programmes. The study's findings contributed to the growing body of knowledge about the association between malnutrition and diagnosed drug-susceptible TB among children aged from 0 - 15 years.

Safety and immunogenicity of the H56:IC31 tuberculosis vaccine candidate in adults successfully treated for drug-susceptible pulmonary TB: a phase 1 randomized trial.

H56:IC31 is a candidate vaccine against tuberculosis (TB) with the potential to reduce TB recurrence rate. It is thus important for future clinical trials to demonstrate safety and immunogenicity of H56:IC31 in individuals treated for TB. 22 adults confirmed to be Mtb negative (by 2 GeneXpert tests or 2 sputum cultures) after four-five months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive two doses of H56:IC31 (5 mg H56:500 nmol IC31; N=16) or placebo (N=6) 56 days apart. Participants were followed for 420 days for safety and immunogenicity. H56:IC31 vaccination was associated with an acceptable safety profile, consisting mostly of mild self-limited injection site reactions. No serious adverse events, and no vaccine-related severe adverse events, were reported. H56:IC31 induced a CD4+ T-cell response for Ag85B and ESAT-6, with ESAT-6 being immunodominant, which persisted through six months after the last vaccination. There was some evidence of CD8+ T-cell responses for both Ag85B and ESAT-6, but to a lesser extent than CD4+ responses. H56:IC31 was associated with an acceptable safety profile, and induced a predominant CD4+ T-cell response, in adults recently treated for drug-susceptible, uncomplicated pulmonary TB. ClinicalTrials.gov, NCT02375698.

Haematological parameter among drug resistant tuberculosis patients in Ibadan

Background: Haematological abnormalities are common among tuberculosis patients but there is dearth of information on their value as prognostic markers in multidrug resistant tuberculosis patients. This study examined the association between complete blood count variables and drug resistant tuberculosis.&#x0D; Materials and methods: Nighty (90) consenting adults comprising 30 Drug Resistant Tuberculosis patients (DR-TB), 30 Drug susceptible tuberculosis patients (DS-TB) and 30 healthy participants were recruited in this study. Ethical approval was obtained from Oyo State Ministry of Health Institutional Review Board while patients’ demographic data were collected using structured questionnaire. Five milliliters (5mL) of blood samples were collected in EDTA bottle. Haematological parameters were analysed using impedance technique and Mindary-BG5380 5-part automated system.&#x0D; Result: The mean hemoglobin levels were significantly lower in DR-TB patients (11.70 ± 2.73 g/dL) than in DS-TB patients (8.33 ± 9.56 fL), with a mean difference of -3.37 ± 12.29 g/dL. The mean MCH and MCHC levels were also slightly lower in DR-TB patients (26.17 ± 3.44 pg and 30.41 ± 1.92 g/dL, respectively), but the differences were not statistically significant. The WBC count was similar in both groups (8.20 ± 3.80 × 10^9 /L and 8.45 ± 3.63 × 10^9 /L, respectively).&#x0D; Conclusion: The mean hemoglobin levels were significantly lower in DR-TB patients than in DS-TB patients which may be due to the increased inflammation associated with DR-TB. The WBC count was similar in both groups, suggesting that the immune system is responding similarly to the infection in both DR-TB and DS-TB patients.Recommendation: In the meantime, healthcare providers should be aware of these potential differences and use them to inform their diagnosis and treatment of patients with tuberculosis.&#x0D; Keywords: Haematological parameters; drug resistant tuberculosis; Ibadan.

Assessing efficacy in non-inferiority trials with non-adherence to interventions: Are intention-to-treat and per-protocol analyses fit for purpose?

Non-inferiority trials comparing different active drugs are often subject to treatment non-adherence. Intention-to-treat (ITT) and per-protocol (PP) analyses have been advocated in such studies but are not guaranteed to be unbiased in the presence of differential non-adherence. The REMoxTB trial evaluated two 4-month experimental regimens compared with a 6-month control regimen for newly diagnosed drug-susceptible TB. The primary endpoint was a composite unfavorable outcome of treatment failure or recurrence within 18 months post-randomization. We conducted a simulation study based on REMoxTB to assess the performance of statistical methods for handling non-adherence in non-inferiority trials, including: ITT and PP analyses, adjustment for observed adherence, multiple imputation (MI) of outcomes, inverse-probability-of-treatment weighting (IPTW), and a doubly-robust (DR) estimator. When non-adherence differed between trial arms, ITT, and PP analyses often resulted in non-trivial bias in the estimated treatment effect, which consequently under- or over-inflated the type I error rate. Adjustment for observed adherence led to similar issues, whereas the MI, IPTW and DR approaches were able to correct bias under most non-adherence scenarios; they could not always eliminate bias entirely in the presence of unobserved confounding. The IPTW and DR methods were generally unbiased and maintained desired type I error rates and statistical power. When non-adherence differs between trial arms, ITT and PP analyses can produce biased estimates of efficacy, potentially leading to the acceptance of inferior treatments or efficacious regimens being missed. IPTW and the DR estimator are relatively straightforward methods to supplement ITT and PP approaches.

Improvement of Organizational Measures for Detection and Diagnosing of Tuberculous Infection and Tuberculosis in Adolescents in the Republic of Kazakhstan

The objective: to improve organizational measures for detection and diagnosing of tuberculous infection and tuberculosis in adolescents in the Republic of Kazakhstan.Subjects and Methods. Screening was conducted among 27,648 adolescents aged 15-17 years from regions of the Republic of Kazakhstan with a high burden of tuberculosis. It was planned to use TRA tests and fluorography in parallel, while local doctors, district and school nurses, and nurses in vaccination rooms were preliminary trained by pediatric phthisiologists to perform the test, evaluate its results and monitor manifestations of adverse events (AEs) caused by TRA test.Results. 27,648 adolescents (aged 15-17 years) were given TRA test. No adverse events were observed during TRA skin test. Latent tuberculous infection was diagnosed in 320 (1.2%) adolescents. During further examination, 10 patients were diagnosed with drug susceptible pulmonary tuberculosis with no bacillary excretion. Based on the study results, to detect LTBI and tuberculosis in adolescents, in addition to fluorography examination, it is necessary to use TRA skin test with in the groups facing a high risk of tuberculosis.

Singapore tuberculosis (TB) clinical management guidelines 2024: A modified Delphi adaptation of international guidelines for drug-susceptible TB infection and pulmonary disease

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore’s clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

Singapore tuberculosis (TB) clinical management guidelines 2024: A modified Delphi adaptation of international guidelines for drug-susceptible TB infection and pulmonary disease

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore’s clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

Assessment of treatment outcome among HIV positive tuberculosis patients in Visakhapatnam

In March 2016, RNTCP revised its technical and operational guidelines. One of the major additions was introduction of Daily Regimen in the treatment of Drug sensitive TB, started initially among TB-HIV co-infected patients in 2017. The present study was taken up to assess the treatment outcomes of Tuberculosis among TB-HIV co-infected patients and certain factors related to the poorer outcome of the treatment.An Observational Longitudinal study conducted at an ART centre, attached to King George Hospital in Visakhapatnam District, Andhra Pradesh, among all TB-HIV co-infected patients newly diagnosed with Drug Susceptible Tuberculosis, aged above 18years, at the selected ART centre, from the month of June 2018 to December 2018. The sample size calculated was 88 with an absolute precision of 10. Ethical clearance from Institutional Ethics Committee, Andhra Medical College; Written informed consent from all the study participants were taken prior to start of study. Confidentiality of the study participants was maintained Qualitative variables were presented as proportions. Analytical statistics include chi-square test and regression analysis. 74% of the patients had a favourable treatment outcome, 15% of the patients died and 11% of the patients were lost to follow up. Occupational status of the study participant, Socio- economic class, tobacco using habit and their CD4 counts had a statistically significant impact on their TB treatment outcome.CD4 count below 200cells/mm, Tobacco use, Diabetes Mellitus- factors responsible for unfavourable treatment outcome of Tuberculosis treatment Case-specific approaches among LFUs may be carried out to bring improvements in the strategies which are already existing or framing new strategies.

Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption. We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant. Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%). Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

Exploring Variability in Rifampicin Plasma Exposure and Development of Anti-Tuberculosis Drug-Induced Liver Injury among Patients with Pulmonary Tuberculosis from the Pharmacogenetic Perspective.

Genetic polymorphisms can exert a considerable impact on drug pharmacokinetics (PK) and the development of adverse drug reactions (ADR). However, the effect of genetic polymorphisms on the anti-tuberculosis (anti-TB) drug, and particularly rifampicin (RIF), exposure or anti-TB drug-induced liver injury (DILI) remains uncertain. Here, we evaluated the relationship between single nucleotide polymorphisms (SNPs) detected in the RIF pharmacogenes (AADAC, SLCO1B1, SLCO1B3, ABCB1, and NR1I2) and RIF PK parameters, as well as anti-TB treatment-associated DILI. In total, the study enrolled 46 patients with drug-susceptible pulmonary TB. The RIF plasma concentration was measured using the LC-MS/MS method in the blood samples collected pre-dose and 2 and 6 h post-dose, whilst the DILI status was established using the results from blood biochemical analysis performed before and 10-12 days after treatment onset. The genotyping was conducted using a targeted NGS approach. After adjustment for confounders, the patients carrying the rs3732357 GA/AA genotype of the NR1I2 gene were found to have significantly lower RIF plasma AUC0-6 h in comparison to those with GG genotype, while the difference in RIF plasma Cmax was insignificant. None of the analyzed SNPs was related to DILI. Hence, we are the first to report NR1I2 intronic SNP rs3732357 as the genetic component of variability in RIF exposure. Regarding anti-TB treatment-associated DILI, the other preexisting factors promoting this ADR should be considered.

Pharmacokinetic-Pharmacodynamic Evidence from a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.

The optimal dosing strategy for rifampicin in treating drug-susceptible tuberculosis (TB) is still highly debated. In the Phase 3 clinical trial Study 31/ACTG 5349 (NCT02410772), all participants in the control regimen arm received 600 mg rifampicin daily as a flat dose. Here, we evaluated relationships between rifampicin exposure and efficacy and safety outcomes. We analyzed rifampicin concentration time profiles using population nonlinear mixed-effects models. We compared simulated rifampicin exposure from flat- and weight-banded dosing. We evaluated the effect of rifampicin exposure on stable culture conversion at 6 months, TB-related unfavorable outcomes at 9, 12, and 18 months using Cox proportional hazard models, and all trial-defined safety outcomes using logistic regression. Our model derived rifampicin exposure ranged from 4.57 mg·h/L to 140.0 mg·h/L with a median of 41.8 mg·h/L. Pharmacokinetic simulations demonstrated that flat-dosed rifampicin provided exposure coverage similar to weight-banded dose. Exposure-efficacy analysis (N=680) showed that participants with rifampicin exposure below the median experienced similar hazards of stable culture conversion and TB-related unfavorable outcomes compared to those with exposure above the median. Exposure-safety analysis (N=722) showed that increased rifampicin exposure was not associated with increased grade 3 or higher adverse events, or serious adverse events. Flat-dosing of rifampicin at 600 mg daily may be a reasonable alternative to the incumbent weight-banded dosing strategy for the standard of care 6-month regimen. Future research should assess the optimal dosing strategy for rifampicin, at doses higher than the current recommendation.

DETERMINING THE DEMOGRAPHIC PATTERNS OF DRUG-RESISTANT AND DRUG-SUSCEPTIBLE TUBERCULOSIS IN KPK, PAKISTAN THROUGH A RETROSPECTIVE SURVEY

Objectives: The objective of this research was to find out the demographic characteristics of drug-susceptible and drug-resistant Tuberculosis in Khyber Pakhtunkhwa, Pakistan. Material and Methods: A retrospective survey was conducted on data from the TB Control Program Khyber Pakhtunkhwa recorded between 1st January 2021 to 3rd June 2022. 7 sentinel sites and 5 Programmatic Management of Drug-resistant Tuberculosis sites report the data to the TB control program. The data was entered into Excel and analyzed through frequency tables, histograms, and bar charts. Results: A total of 39,210 Tuberculosis cases were reported to TB control program KPK from 1st January 2021 to 3rd June 2022; 38,723 were drug-susceptible while 487 were drug-resistant TB cases. The highest percentage of TB was found in the age group 15-24 years. Males were more affected than females with drug-susceptible TB. In contrast, drug-resistant TB was affecting females more than males.  58% of cases were reported in the public sector while 42% cases in the private sector. The households of only 2,412 (6.22%) patients of drug-susceptible Tuberculosis were screened out of 38,723 patients. In 2815 Tuberculosis patients screened for HIV, 4 drug-susceptible and 5 drug-resistant cases were positive for HIV. 8.41% of drug-resistant TB patients were diabetic. Conclusion: The frequency of TB cases is high in Khyber Pakhtunkhwa, especially among 15-24-year-olds. Household contact screening is inadequate in Khyber Pakhtunkhwa. There is a high percentage of coexisting drug-resistant TB and diabetes. Keywords: Drug susceptible TB, Drug-resistant TB, HIV co-infection, Household contact.  

The prevalence, clinical reasoning and impact of non-standard anti-tuberculosis regimens at the initial prescription

Regarding clinically-concerning non-standard initial anti-tuberculous (TB) regimens, few studies have examined their prevalence, risk factors and impacts. We recruited patients with drug susceptible TB and non-standard initial anti-TB regimens (NSTB group) and matched them with patients with standard initial regimens (STB group) in a 1:1 ratio. The risk factors and outcomes were analyzed. During the 11-year study period, we analyzed 50 (3.7%) patients with NSTB from a total set of 1337 patients with drug-susceptible TB. Pyrazinamide (60%) was the drug most commonly not prescribed in the NSTB group, followed by ethambutol (34%). Multivariable logistic regression identified independent risk factors as underlying eye disease (adjusted odds ratio [aOR]: 8.869; 95% CI 2.542–30.949; p = 0.001), gout/hyperuricemia (aOR: 4.012 [1.196–13.425]; p = 0.024), and liver disease (aOR: 12.790 [3.981–41.089]; p < 0.001). The NSTB group had longer treatment durations (281 ± 121 vs. 223 ± 63 days; p = 0.003) and more occurrences of treatment interruption (26% vs. 8%; p = 0.021) than the STB group. In conclusion, NSTB occurs in around 3.7% of patients and is associated with longer treatment and more treatment interruption. The risk factors might include underlying liver and eye diseases, and gout. Further studies to improve non-standard initial regimens and prevent negative outcomes are warranted.

Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

2022 TB programme review in Pakistan: strengthening governance, with better patient diagnosis and treatment

&lt;sec&gt;&lt;title&gt;BACKGROUND&lt;/title&gt;In Pakistan, 84% of healthcare is provided by the private sector. We conducted an epidemiological and programme review for TB to document progress and guide further efforts.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;METHODS&lt;/title&gt;Surveillance and data systems were assessed before analysing epidemiological data. We reviewed the programme at federal, provincial and peripheral levels and compiled national data along with WHO estimates to describe the evolution of epidemiological and programme indicators.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;RESULTS&lt;/title&gt;In 2021, of the estimated number of TB cases, 55% of overall cases and 18% of drug-resistant cases were diagnosed and treated respectively. The contribution of the private sector in case detection increased from 30% in 2017 to 40% by 2021. For newly diagnosed pulmonary TB cases, the overall proportion of confirmed cases was 52%. In 2021, testing for rifampicin resistance among confirmed cases was 66% for new and 84% for previously treated patients. The treatment success rate exceeded 90% for drug susceptible TB. The main challenges identified were a funding gap (60% in 2021–2023), fragmented electronic systems for data collection and suboptimal coordination among provinces.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;CONCLUSIONS&lt;/title&gt;The main challenges prevent further progress in controlling TB. By addressing these, Pakistan could improve coverage of interventions, including diagnosis and treatment. Bacteriological confirmation using recommended diagnostics also requires further optimisation.&lt;/sec&gt;

Pyrazinamide resistance due to pncA gene mutation and its association with treatment outcome among tuberculosis patients of South India- A longitudinal observational study

IntroductionMycobacterium tuberculosis has been extensively studied for mutations leading to drug resistance. Pyrazinamide is a drug acting on the semi-dormant bacteria that is responsible for relapse of tuberculosis. This drug helped reduce the treatment duration of tuberculosis from nine to six months. However, this drug is not being screened for resistance along with Rifampicin and Isoniazid. Aims and objectivesThis study aimed to estimate the proportion of pncA gene mutation among tuberculosis patients and its association between treatment outcomes, clinical characteristics, and phenotypic drug resistance. Methodology: A total of 154 samples included 73 drug-resistant and 81 drug-susceptible isolates. The isolates were subjected to DNA extraction and amplification using conventional PCR. The PCR product was sequenced by the Sanger sequencing method, and phenotypic drug susceptibility testing was done using the broth dilution method. The association of this gene with the treatment outcome was done by following up with the patients till the end of the regimen. ResultsNone of the drug susceptible tuberculosis patients showed significant non-synonymous mutations. Among the drug-resistant TB patients, seven unique significant mutations out of 73 isolates (9.6%) were distributed among Isoniazid-resistant tuberculosis and Multi-Drug Resistant Tuberculosis isolates. No association was found between the mutations and the clinical characteristics of the subjects harboring these isolates. ConclusionThis study estimated seven unique mutations in drug-resistant tuberculosis and none in drug-sensitive tuberculosis. Isolates harboring was not significantly associated with the participant's treatment outcome and other clinical characteristics. The pyrazinamide resistance testing by the phenotypic and genotypic methods was found to be in concordance.