Drug-resistant Tuberculosis Patients Research Articles

Latent Demographic and Clinical Correlates of Drug Resistant Tuberculosis Among Treated Patients

Demographic and Clinical variables (data) collected from tuberculosis patients whose cases were drug resistant were analysed. The tuberculosis patients studied were those treated in the 11 Local Governments Areas and a treatment centre of Anambra State, Nigeria, for six years (2017 – 2022). Data from 197 Drug Resistant Tuberculosis (DR-TB) patients were analysed. The pair of data collected, being multivariate in nature, were analysed using the Canonical Correlation Analysis (CCA) and the Canonical loadings (structure coefficients) between the Demographic and Clinical Variables were extracted. Data obtained showed that mean age of the study participants was 40.2 ± 18.9 years (95% Confidence Interval). Males were 60.9%. Participants with HIV co-infection was 22.3%. The CCA showed that the first canonical variate was significant with 79% contribution, extracting 28.5% of the variance from demographic variables and 6.7% variance from the clinical variables. The variables that significantly contributed to the relationship include Age, Location and Body Mass Index (BMI). Human Immuno-Deficiency Virus (HIV) negative was protective in the relationship but not statistically significant.

Catastrophic costs incurred by tuberculosis affected households from Thailand’s first national tuberculosis patient cost survey

Tuberculosis (TB) causes an economic impact on the patients and their households. Although Thailand has expanded the national health benefit package for TB treatment, there was no data on out-of-pocket payments and income losses due to TB from patients and their household perspectives. This national TB patient cost survey was conducted to examine the TB-related economic burden, and assess the proportion of TB patients and their households facing catastrophic total costs because of TB disease. A cross-sectional TB patient cost survey was employed following WHO methods. Structured interviews with a paper-based questionnaire were conducted from October 2019 to July 2021. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2021 and estimated throughout pre- and post-TB diagnosis episodes. We assessed the proportion of TB-affected households facing costs > 20% of household expenditure due to TB. We analyzed 1400 patients including 1382 TB (first-line treatment) and 18 drug-resistant TB patients (DR-TB). The mean total costs per TB episode for all study participants were 903 USD (95% confident interval; CI 771–1034 USD). Of these, total direct non-medical costs were the highest costs (mean, 402 USD, and 95%CI 334–470 USD) incurred per TB-affected household followed by total indirect costs (mean, 393 USD, and 95%CI 315–472 USD) and total direct medical costs (mean, 107 USD, and 95%CI 81–133 USD, respectively. The proportion of TB-affected households facing catastrophic costs was 29.5% (95%CI 25.1–34.0%) for TB (first-line), 61.1% (95%CI 29.6–88.1%) for DR-TB and 29.9% (95%CI 25.6–34.4%) overall. This first national survey highlighted the economic burden on TB-affected households. Travel, food/nutritional supplementation, and indirect costs contribute to a high proportion of catastrophic total costs. These suggest the need to enhance financial and social protection mechanisms to mitigate the financial burden of TB-affected households.

Comparison of QTc interval changes in drug-resistant tuberculosis patients on delamanid-containing regimens versus shorter treatment regimens.

Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). A retrospective cohort was implemented on secondary data obtained from two participating hospitals. The QTc interval and the changes in QTc interval from baseline (ΔQTc) were assessed every 4 weeks for 24 weeks. The maximum increased of QTc interval and ΔQTc interval were smaller in the DLM group with mean difference of 18,6 (95%CI 0.3 to 37.5) and 31.6 milliseconds (95%CI 14.1 to 49.1) respectively. The proportion of QTc interval prolongation in DLM group were smaller than STR group (RR=0.62; 95%CI 0.42 to 0.93). This study has shown that DLM regimens are less likely to increase QTc interval compared to STR. However, close monitoring of the risk of QT interval prolongation needs to be carried out upon the use of QT interval prolonging antituberculoid drugs.

Epidemiology and outcomes of drug-resistant tuberculosis cases notified in a low-resource district in Kerala, India 2017–2021 – A 5-year retrospective analysis

Objectives: Kasaragod district reports the highest drug-resistant tuberculosis (DR-TB) case notification rates in Kerala. We conducted a cross-sectional study in Kasaragod to describe the DR-TB cases notified from January 2017 to December 2021 and to identify the factors associated with unfavorable treatment outcomes in DR-TB patients. Materials and Methods: We analyzed the programmatic data from the “Nikshay portal” (a web-based patient management information system for [TB] under the National TB Elimination Program), DR-TB treatment cards, and treatment registers available with the district TB center for all the DR-TB patients notified during the study period. We described the DR-TB cases by year, local self-government area (the local administrative setup), age, gender, income level, and treatment outcomes. We compared sociodemographic, anthropometric, and clinical factors among the DR-TB patients with favorable (cured and treatment completed) and unfavorable (died, lost to follow-up, and treatment failure) treatment outcomes. Results: From January 2017 to December 2021, 128 DR-TB cases were notified from Kasaragod. Annual notification rates varied from 1.4 to 3.4/100,000 population with the highest notification in 2019. The proportion of new TB cases notified tested for drug sensitivity rose from 22% in 2017 to 86% in 2021. Seven of 41 local self-government areas had not notified DR-TB cases during 2017–2021. The notification was higher in inter-state border areas and the coastal belt of the district. The notification of DR-TB cases was highest among the 45–59 age group (17/100,000), followed by the 60 above group (11/100,000). Males and those living below the poverty line had higher notification rates. Among the outcomes evaluated 118 DR-TB patients, 89 (75.4%) had favorable outcomes, whereas the remaining 24.6% had unfavorable outcomes (death 18 [15.3%], loss to follow-up 7 [6%], and treatment failure 4 [3.4%]). Age more than 45 years adjusted odds ratio (aOR) 3.1 (95% confidence interval [CI] 1.1–8.8), income category below the poverty line aOR 6 (95% CI 1.2–28.6), admitted at least twice during treatment aOR 9.2 (95% CI 2.8–30.3), and body mass index at diagnosis <18.5 kg/m2 aOR 3 (95% CI 1.1–10.3) were found to be significantly associated with unfavorable treatment outcomes. Conclusion: DR-TB notifications have increased in the Kasaragod district from 2017 to 2021, with a high burden among males aged 45 years and above. The favorable treatment outcome is better than the national and state average. Regular monitoring and follow-up of multidrug-resistant patients with low incomes, above 45 years, and underweight may improve the final treatment outcomes.

Development of a multiplex droplet digital PCR method for detection and monitoring of Mycobacterium tuberculosis and drug-resistant tuberculosis

BackgroundThe prevalence of multidrug-resistant tuberculosis (MDR-TB) among Korean tuberculosis patients is about 4.1%, which is higher than the OECD average of 2.6%. Inadequate drug use and poor patient compliance increase MDR-TB prevalence through selective pressure. Therefore, prompt detection of drug resistance in tuberculosis patients at the time of diagnosis and quantitative monitoring of these resistant strains during treatment are crucial.MethodsA multiplex droplet digital PCR (ddPCR) assay was developed and assessed using DNA material of nine Mycobacterium tuberculosis strains with known mutation status that were purchased from the Korean National Tuberculosis Association. We collected a total of 18 MDR-TB residual samples referred for PCR analysis. Total DNA was extracted from the samples and subjected to the quadruplex ddPCR assay. Their results were compared to those of known resistance phenotypes.ResultsThe analytical sensitivity and specificity of the multiplex ddPCR assay for detecting INH, RIF, EMB, FQ, and SM resistance-causing mutations ranged from 71.43 to 100% and 94.12–100%, respectively. Follow-up sample results showed that the quadruplex ddPCR assay was sensitive enough to detect IS6110 and other mutations even after onset of treatment.ConclusionsWe developed a sensitive and accurate multiplex ddPCR assay that can detect the presence of tuberculosis quantitatively and resistance-conveying mutations concurrently. This tool could aid clinicians in the diagnosis and treatment monitoring of tuberculosis.

Эпидемиологические аспекты формирования новых рисков заболеваемости и лечения туберкулеза среди населения.

In accordance with the instruction of the Minister of Health of the Russian Federation No. 19 dated 02/07/2023, specialists currently face several important tasks: from 2015 to 2025, to reduce the incidence of tuberculosis, as well as the number of deaths from tuberculosis by 75%. To do this, it is necessary to identify all the risk factors that may create difficulties in achieving these goals. Purpose of the study is to characterize the epidemiological aspects of the formation of new risks of morbidity and treatment of tuberculosis among the population. Materials and methods. An analysis was carried out among newly identified patients with tuberculosis by molecular genetic (n=1682) and bacterial (n=1630) research methods in the period from 2017 to 2020 according to drug resistance indicators. Results. It was found that in the period from 2015 to 2017, the indicators of drug resistance in tuberculosis patients were almost at the same level. The leading antimicrobial drugs in demand among the population were ceftriaxone, azithromycin, levofloxacin, moxifloxacin. The maximum increase in sales in 2020 relative to 2019 data to 150% was determined among quinolone derivatives of moxifloxacin and levofloxacin, which began to be used in the treatment of coronavirus infection. At the same time, these drugs are traditionally used to treat tuberculosis, but in 2020, an alarming trend was revealed, which was that drug resistance was detected in patients with tuberculosis to these drugs. Among newly diagnosed tuberculosis patients, from 2018 to 2020, an increase in the proportion of patients with primary drug resistance to levofloxacin and moxifloxacin was established by 189-480%; whereas for other antibiotics, the increase averaged up to 60.8%. Findings. The findings suggest an alarming scenario in which drug resistance develops towards highly virulent and highly resistant to antibacterial drugs genotypes.

The clinical profile and outcomes of drug resistant tuberculosis in Central Province of Zambia

BackgroundThe emergence of Drug Resistant Tuberculosis (DR-TB) is one of the main public health and economic problems facing the world today. DR-TB affects mostly those in economically productive years and prevents them from being part of the workforce needed for economic growth. The aim of this study was to determine the Clinical Profile and Outcomes of DR-TB in Central Province of Zambia.MethodsThis was a retrospective cross sectional study that involved a review of records of patients with confirmed DR-TB who were managed at Kabwe Central Hospital’s Multi-Drug Resistant TB (MDR-TB) Ward from the year 2017 to 2021. 183 patients were managed during this period and all were recruited in the study. Data was collected from DR-TB registers and patient files and then entered in SPSS version 22 where all statistical analyses were performed.ResultsThe study revealed that the prevalence of DR-TB among registered TB patients in Central Province was 1.4%. Majority of those affected were adults between the ages of 26 and 45 years (63.9%). The study also found that more than half of the patients were from Kabwe District (60.7%). Other districts with significant number of cases included Kapiri Mposhi 19 (10.4%), Chibombo 12 (6.6%), Chisamba 10 (5.5%), Mumbwa 7 (3.8%) and Mkushi 7 (3.8%). Furthermore, the analysis established that most of the patients had RR-TB (89.6%). 9.3% had MDR-TB, 0.5% had IR-TB and 0.5% had XDR-TB. RR-TB was present in 93.8% of new cases and 88.9% of relapse cases. MDR-TB was present in 6.2% of new cases and 10% of relapse cases. With regard to outcomes of DR-TB, the investigation revealed that 16.9% of the patients had been declared cured, 45.9% had completed treatment, 6% were lost to follow up and 21.3% had died. Risk factors for mortality on multivariate analysis included age 36–45 years (adjusted odds ratio [aOR] 0.253, 95% CI [0.70–0.908] p = 0.035) and male gender (aOR 0.261, 95% CI [0.107–0.638] p = 0.003).ConclusionThe research has shown beyond doubt that the burden of DR-TB in Central Province is high. The study recommends putting measures in place that will help improve surveillance, early detection, early initiation of treatment and proper follow up of patients.

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.
 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.
 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).
 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.
 Keywords: Haematological parameters; drug resistant tuberculosis; Ibadan.

Decentralised ECG monitoring for drug-resistant TB patients in ambulatory settings

Decentralised ECG monitoring for drug-resistant TB patients in ambulatory settings

Determinants of Treatment Delay in Drug-Resistant Tuberculosis Patients in Banten Province in 2020

Indonesia is currently ranked 2nd with the most tuberculosis cases in the world, after India and China. is ranked 2nd with the most tuberculosis sufferers in the world, after India and China.
 Tuberculosis control in Indonesia faces many challenges, one of which is the increase in patients
 with drug-resistant tuberculosis (DR TB). In 2019, the number of tuberculosis sufferers in Indonesia
 reached 543,874 cases, with drug-resistant tuberculosis cases reaching 11,463 (2.1%). Banten is
 one of the provinces with the highest number of Tuberculosis sufferers in Java, which is 223 people
 per 100,000 population, with a national TB rate of 203 people per 100,000 population, of which
 only 58.3% take medication regularly. This study aims to determine the determinants of treatment
 delay in drug-resistant tuberculosis patients in Banten province in 2020. The study design was a
 retrospective cohort. The sampling technique was a total sampling of the list of DR TB cases at
 South Tangerang city General Hospital and dr. Drajat Prawiranegara Serang. Secondary data
 search was carried out on the TB Information System (SITB) and patient medical records. The study
 population was 114 respondents, obtained 90 respondents who fit the inclusion and exclusion
 criteria. Univariate, bivariate analysis with chi-square test and multivariate with logistic regression
 statistical test were performed to obtain a fit final model. The results of the bivariate analysis
 showed a significant relationship between age (p=0.030) and employment status (p=0.003). The
 final multivariate model, showing employment status with delayed treatment (p = 0.008), with OR
 18,788 (95% CI: 2,122 – 166.329), meaning that respondents who have jobs have 18.8 times risk for
 late treatment compared to respondents who do not have jobs after being controlled by variables
 of age, gender, history of TB, and education level. The researcher concludes that the determinants
 of delay in treatment of DR TB patients in Banten province in 2020 are employment status and age.
 It is recommended that the Banten Provincial Health Office can coordinate cross sectors, to ensure the treatment of DR TB patients until they are cured.
 Keywords: epidemiology, tuberculosis, drug-resistant

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.

Incidence and risk factors of myelosuppression of linezolid in patients with drug-resistant tuberculosis: A scoping review

Background: Drug-resistant tuberculosis (DR-TB) poses a significant global health challenge, requiring prolonged treatment with multiple second-line anti-tuberculosis drugs. Among these medications, bedaquiline and linezolid have shown promising outcomes. However, the primary adverse effects of linezolid leading to dose reduction or early discontinuation is myelosuppression. Methods: This study involved a comprehensive review to evaluate the incidence and risk factors of linezolid-induced myelosuppressionin patients with DR-TB in bedaquiline-based regimens. Furthermore, the procedure adhered to the Systematic Reviews and Meta-Analyses (PRISMA) guideline for a scoping review. Results: The results showed that nine cohort studies met the inclusion criteria. Among the 3310 DR-TB patients in these studies, 661 (19.9%) had HIV. The incidence of myelosuppression ranged from 5.1% to 49.0%, with anemia being the most prevalent case, ranging from 2.9% to 39.0%. According to the reports, linezolid interruption, such as dose adjustments or complete discontinuation ranged from 20.5% to 23.6%. Myelosuppression occurred within a period less than three months on average. Several factors were identified as influencing myelosuppression (anemia) in DR-TB patients within these regimens, including age ≥ 60, concurrent treatment with zidovudine in HIV positive patients, and linezolid concentrations > 2 mg/L. No studies reported mortality cases associated with linezolid. Conclusions: The incidence of myelosuppression was relatively high in DR-TB patients with regimen containing linezolid. Anemia was the most prevalent symptom of myelosuppression during treatment, leading to early discontinuation of linezolid. It indicates that hematologic parameter should be closely supervised, especially in patients with risk factors during linezolid treatment.

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.

Lysosomal enzymes and the oxygen burst capability of monocyte-derived macrophages in active drug-resistant tuberculosis patients in relation to cell attachment

Drug resistance to tuberculosis (TB) has become an obstacle in eliminating tuberculosis. The transmission of drug-resistant TB from patients increases the incidence of primary drug-resistant (DR) TB in individuals who are in close contact. Therefore, it is necessary to incorporate an immunological approach into preventive therapy. This study focuses on the activity of lysosomal enzymes, oxygen bursts, and the attachment ability of macrophages among individuals diagnosed with active drug-resistant TB compared with close contacts with latent TB or healthy cases. We measured macrophage oxygen burst ability (Water-soluble tetrazolium salt (WST) test, Nitric Oxide production, and myeloperoxidase activity) and the degradative ability of lysosomes (activity of the β-glucuronidase and acid phosphatase enzymes). Six active DR-TB patients and 18 close-contact cases (8 Latent Tuberculosis Infection (LTBI); 10 healthy) were recruited at Universitas Indonesia Hospital. The macrophage attachment of the LTBI group was higher than in the other groups. NO production, myeloperoxidase activity, β-glucuronidase, and acid phosphatase were higher in the active DR-TB group. A negative correlation was uncovered between phagocytosis and NO production, myeloperoxidase activity, and lysosomal enzymes. The difference in macrophage function is expected to be a further reference in active DR-TB treatment or preventive therapy.

Time to sputum culture conversion and its associated factors among drug-resistant tuberculosis patients: a systematic review and meta-analysis

ObjectiveWe aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors.MethodsPubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software.ResultsA total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1+) (aHR = 0.87,95%CI:0.77,0.99), (grade 2+) (aHR = 0.81,95%CI:0.69,0.95), (grade 3+) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB.ConclusionPatients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m2, lung cavity, sputum smear grading at baseline (Positive, grade 1+, grade 2+, grade 3+) may be risk factors for longer sputum culture conversion time.This systematic review has been registered in PROSPERO, the registration number is CRD42023438746.

Vitamin D, Body Mass Index, and Total Lymphocyte Count in Drug-Sensitive and Drug-Resistant Tuberculosis Patients in Banjarmasin

Introduction: Tuberculosis (TB) remains a global health problem that causes high morbidity and mortality. Based on its classification, TB is divided into drug-sensitive (DS) and drug-resistant (DR). Several risk factors susceptible to TB are malnutrition with low body mass index (BMI), vitamin D deficiency (VDD), and low total lymphocyte count (TLC) related to low immune status. This study aimed to examine the relationship between vitamin D (VD), BMI, and TLC in the TB population in Banjarmasin. Methods: This was an analytic observational study with a cross-sectional design. The total study sample was 42 patients, confirmed by rapid molecular testing, who had not been treated for TB in Banjarmasin from January to May 2023 and met the inclusion and exclusion criteria. Chi-Square and Fisher's exact statistical tests were used to see the relationship between VD, BMI, and TLC in DS TB and DR TB. Results: The median age of DS TB was 38 (24-52) years old, and DR TB was 51 (37-58) years old. Most of the gender was male (24 patients/57.1%). There was a statistically significant difference between VD and BMI in DS TB and DR TB (p = 0.048; p = 0.019). There was a significant relationship between VD and TLC in DS TB and DR TB (p = 0.048). Conclusion: VD and BMI significantly differed in DS TB and DR TB. There was a significant correlation between VD and TLC in TB patients.

Healthcare seeking behavior and delays in case of Drug-Resistant Tuberculosis patients in Bangladesh: Findings from a cross-sectional survey.

The emergence of Drug-Resistant Tuberculosis (DR-TB) has become a major threat globally and Bangladesh is no exception. Delays in healthcare seeking, proper diagnosis and initiation of treatment cause continuous transmission of the resistant tubercule bacilli through the communities. This study aimed to assess the different health care-seeking behaviors and delays among DR-TB patients in Bangladesh. A prospective cross-sectional study was conducted from November to December 2018, among 92 culture positive and registered DR-TB patients in four selected hospitals in Bangladesh. Data were collected through face-to-face interviews with survey questionnaire as well as record reviews. Among the 92 study participants, the median patient delay was 7 (IQR 3, 15) days, the median diagnostic delay was 88 (IQR 36.5, 210), the median treatment delay was 7 (IQR 4,12) days, and the median total delay among DR-TB patients was 108.5 (IQR 57.5, 238) days. 81.32% sought initial care from informal healthcare providers. The majority (68.48%) of the informal healthcare providers were drug sellers while 60.87% of patients sought care from more than four healthcare points before being diagnosed with DR-TB. The initial care seeking from multiple providers was associated with diagnostic and total delays. In Bangladesh, DR-TB cases usually seek care from multiple providers, particularly from informal providers, and among them, alarmingly higher healthcare-seeking related delays were noted. Immediate measures should be taken both at the health system levels and, in the community, to curb transmission and reduce the burden of the disease.

Toll-like receptor 2 (-196 to -174) del and TLR1 743 A > G gene polymorphism-a possible association with drug-resistant tuberculosis in the north Indian population.

The objective of this study is to analyze the association between TLR2 deletion (-196 to -174) and TLR1 743 A > G gene polymorphism with drug resistant tuberculosis (PTB, MDR-TB, and XDR-TB) in a population from Agra, Uttar Pradesh. The present case-control study included 101 pulmonary TB patients, 104 multidrug-resistant TB patients, 48 extremely drug-resistant TB patients, and 130 healthy and unrelated controls residing in the same locality. The genotyping method for TLR2 deletion (-196 to -174) was carried out by allele-specific polymerase chain reaction (PCR), and TLR1 743 A > G gene polymorphism was performed by hybridization probe chemistry in Roche Real-Time PCR. Genotype and allele frequencies were analyzed by the chi-square test. Cytokine levels were measured by ELISA and compared using Mann-Whitney and Kruskal-Wallis tests. The frequency of heterozygous (Ins/del) genotypes for TLR2 (-196 to -174) polymorphism was predominant in XDR-TB patients (0.57), whereas heterozygous A/G genotype for TLR1 743 A > G single nucleotide polymorphism (SNP) was predominant in healthy controls (0.57) for TLR1 743 A > G gene polymorphism. The heterozygous genotype of TLR2 deletion polymorphism was found to be significantly higher in XDR-TB (p = 0.0001). TLR1 743 A > G SNP, AG genotypes were found to be significantly associated with healthy controls than PTB (p = 0.047). The level of serum cytokines (IL-6, TNF-α, and IFN-γ) was also found to be significantly different among TB patients and healthy controls. The findings suggested that in the present population, the heterozygous (Ins/Del) genotype and deletion allele of TLR2 deletion (-196 to -174) polymorphism are associated with the risk for the development of drug-resistant TB. Furthermore, for TLR1 743 A > G gene polymorphism, A/G genotype, and G allele are found associated with healthy controls, suggesting the protective role against TB.

Associations between air pollutants and acute exacerbation of drug-resistant tuberculosis: evidence from a prospective cohort study

BackgroundShort-term exposure to air pollution may trigger symptoms of drug-resistant tuberculosis (DR-TB) through stimulating lung tissue, damaging tracheobronchial mucosa, the key anti-mycobacterium T cell immune function, and production and release of inflammatory cytokines.ObjectiveTo investigate the association between acute exacerbations of DR-TB and short-term residential exposure to air pollutants (PM10, PM2.5, SO2, NO2, CO and O3) based on a large prospective cohort in Anhui Province, China.MethodPatients were derived from a prospective cohort study of DR-TB in Anhui Province. All DR-TB patients underwent drug-susceptibility testing and prefecture-level reference laboratories confirmed their microbiologies. The case-crossover design was performed to evaluate the association between the risk of acute exacerbations of DR-TB and short-term residential exposure to air pollution.ResultsShort-term NO2 exposure was significantly related to an elevated risk of first-time outpatient visit due to acute exacerbations of DR-TB(relative risk:1.159, 95% confidence interval:1.011 ~ 1.329). Stratification analyses revealed that the relationship between the risk of acute exacerbations and NO2 exposure was stronger in the elderly (age ≥ 65) DR-TB patients, and in individuals with a history of TB treatment.ConclusionsNO2 Exposure was significantly associated with an elevated risk of acute exacerbation of DR-TB in Anhui Province, China.

Global adoption of 6-month drug-resistant TB regimens: Projected uptake by 2026.

The WHO has issued a call to action urging countries to accelerate the rollout of new WHO-recommended shorter all-oral treatment regimens for drug-resistant TB (DR-TB), which remains a public-health crisis. The all-oral, 6-month BPaL/M regimen comprises 3-4 drugs: pretomanid used in combination with bedaquiline and linezolid, with or without moxifloxacin. This regimen has been recommended by the WHO for use in DR-TB patients instead of ≥9-month (up to 24-month) regimens. This study aims to project this regimen's use, along with its components bedaquiline, pretomanid and linezolid, and other treatments for DR-TB globally through 2026. It is intended to guide global health stakeholders in planning and budgeting for DR-TB interventions. Projected usage could help estimate cost of the individual components of DR-TB regimens over time. Semi-structured interviews were conducted with national TB programme participants in key countries to gather intelligence on established plans and targets for use of various DR-TB treatment regimens from 2023 to 2026. These data informed development of projections for the global use of regimens and drugs. Consistent global growth in the use of shorter regimens in DR-TB treatment was shown: BPaLM reaching 126,792 patients, BPaL reaching 43,716 patients, and the 9-11-month all-oral bedaquiline-based regimen reaching 13,119 patients by 2026. By 2026, the longer all-oral regimen is projected to be used by 19,262 patients, and individualised treatment regimens by 15,344 patients. The study shows BPaL/M will be used in majority of DR-TB patients by 2024, reaching 78% by 2026. However, national efforts to scale-up, case-finding, monitoring, drug-susceptibility testing, and implementation of new treatments will be essential for ensuring they are accessible to all eligible patients in the coming years and goals for ending TB are met. There is an urgent need to engage communities in capacity building and demand generation.