Drug-susceptible Tuberculosis Patients Research Articles

Isoniazid resistance pattern among pulmonary tuberculosis patients in Bangladesh: An exploratory study

ObjectivesIn high tuberculosis (TB) burden countries such as Bangladesh, research and policy tend to focus on rifampicin (RIF)-resistant TB patients, leaving RIF-sensitive but isoniazid (INH)-resistant (Hr-TB) patients undiagnosed. Our study aims to determine the prevalence of INH resistance among pulmonary TB patients in selected health care facilities in Bangladesh. MethodsThis study was conducted across nine TB Screening and Treatment Centres situated in Bangladesh. Sputum samples from 1084 Xpert-positive pulmonary TB patients were collected between April 2021 and December 2022 and cultured for drug susceptibility testing. Demographic and clinical characteristics of Hr-TB and drug-susceptible TB patients were compared. ResultsAmong available drug susceptibility testing results of 998 culture-positive isolates, the resistance rate of any INH regardless of RIF susceptibility was 6.4% (64/998, 95% CI: 4.9–8.2). The rate was significantly higher in previously treated (21.1%, 16/76, 95% CI: 12.0–34.2) compared with newly diagnosed TB patients (5.2%, 48/922, 95% CI: 3.8–6.9) (p < 0.001). The rate of Hr-TB was 4.5% (45/998, 95% CI: 3.3–6.0), which was also higher among previously treated patients (6.6%, 5/76, 95% CI: 1.4–13.5) compared with newly diagnosed TB patients (4.3%; 40/922, 95% CI: 3.1–5.9) (p 0.350). Most importantly, the rate of Hr-TB was more than double compared with MDR-TB (4.5%, 45/998, vs. 1.9%, 19/998) found in the current study. DiscussionThis study reveals a high prevalence of Hr-TB, surpassing even that of the multi-drug-resistant TB in Bangladesh. This emphasizes the urgent need to adopt WHO-recommended molecular tools at the national level for rapid detection of INH resistance so that patients receive timely and appropriate treatment.

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.

Haematological parameter among drug resistant tuberculosis patients in Ibadan.

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. 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. 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). 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. 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.

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.

Possible depression in new tuberculosis patients in the Free State province, South Africa.

Despite compelling evidence of comorbidity between tuberculosis (TB) and depression, little is known about the prevalence and determinants of depression among TB patients in the Free State province in South Africa. This study assessed the prevalence and factors associated with possible depression among new drug susceptible TB patients attending primary health care facilities. The study followed a cross-sectional design. Trained fieldworkers conducted face-to-face interviews with conveniently selected patients. Depression was assessed using the Patient Health Questionnaire-9. Data were subjected to descriptive and binomial logistic regression analyses. Out of 208 patients, 46.2% screened positive for possible depression - 22.6%, 18.8%, and 4.8% presenting with mild, moderate, and severe symptoms, respectively. Possible depression odds were three times higher among females than males (adjusted odds ratio [AOR]: 3.0; 95% confidence interval [CI]: 1.25-7.32) and 2.7 times higher among extrapulmonary TB (EPTB) than pulmonary TB patients (95% CI: 1.03-7.21). Longer TB treatment duration was protective (AOR: 0.8; 95% CI: 0.70-0.95) against depression. Among human immunodeficiency virus-positive patients, those on antiretroviral therapy (ART) had 2.5 times higher odds of depression (95% CI: 1.13-5.46) than those who were not. The results highlight a significant burden of possible depression among new TB patients, particularly among females, EPTB patients, and ART recipients. Longer TB treatment duration may offer some protection against depression symptoms, suggesting a need for enhanced adherence support. The results suggest that strengthening TB and mental health service integration is critical to improving treatment outcomes, overall well-being of TB patients, and the performance of the Free State TB programme.

Case fatality among people with drug-susceptible TB enrolled in a private health sector TB treatment support program in Bihar, India during the first year of the COVID-19 pandemic.

Experiencing 27% of the global tuberculosis (TB) burden, India's TB epidemic is the largest in the world. Due to COVID-19-related disruptions to TB programs, India has also seen the largest drop in TB case notifications of any country globally. We estimated case fatality among people treated for TB in India during the pandemic and compared these to pre-pandemic estimates. A random sample of 4,000 adults enrolled in World Health Partners (WHP), a private sector TB treatment support program (enrolling only people with drug-susceptible TB) in Bihar, India in the first year of COVID-19 (Mar 2020-Mar 2021) were contacted via phone to collect information on TB case fatality and other relevant covariates. Inverse probability of selection (IPS) weighting was used to obtain selection-bias-corrected in-treatment and post-treatment case fatality estimates. Covariates associated with (but not necessarily causal of) case fatality were identified by estimating adjusted hazard ratios (HRs) using the Cox proportional hazards model. WHP enrolled 19,826 adult drug-susceptible TB patients in the first year of COVID-19 (Mar 2020 to Mar 2021). Of our random sample of 4,000 patients, n = 2,962 (74.1%) answered the follow-up call. Unweighted and IPS-weighted in-treatment case fatality in the primary analysis were 6.12% (95%CI: 5.31-6.97%) and 6.07% (95%CI: 5.22-6.93%), respectively. Post-treatment case fatality estimates were 0.97% (95%CI: 0.61-1.33%) (unweighted) and 1.27% (95%CI: 0.79-1.79) (IPS-weighted). Our IPS-weighted estimates for in-treatment and post-treatment case fatality were similar to pre-pandemic IPS-weighted estimates (in-treatment: 7.27%, 95%CI: 5.97%- 8.49% and 12 months post-treatment: 1.23, 95%CI: 0.75-1.73). Although not higher than pre-pandemic estimates, the observed case fatality in this private sector cohort of people treated for drug-susceptible TB during COVID-19 in Bihar, India is above the level needed to reach the 2025 and 2030 End TB Strategy targets for reductions in TB deaths, underlining the extent of pandemic-related setbacks to TB elimination.

Community-supported self-administered tuberculosis treatment combined with active tuberculosis screening: a pilot experience in Conakry, Guinea

ABSTRACT Directly observed treatment (DOT) for tuberculosis (TB) is recommended by the World Health Organization. However, DOT does not always meet patients’ preferences, burdens health facilities, and is hard to implement in settings where access to healthcare services is regularly interrupted. A model addressing these limitations of DOT is community-supported self-administered treatment (CS-SAT), in which patients who self-administer TB treatment receive regular visits from community members. Guinea is a country with a high TB burden, recurrent epidemics, and periodic socio-political unrest. We piloted a CS-SAT model for drug-susceptible TB patients in Conakry, led by community volunteers, who also conducted active TB case finding among household contacts and referrals for isoniazid preventive treatment (IPT) in children below 5 years old. We aimed to assess TB treatment outcomes of patients on CS-SAT and describe the number of patients identified with TB case finding and IPT provision. Prospectively enrolled bacteriologically confirmed TB patients, presenting to two facilities, received monthly TB medication. Community volunteers performed bi-weekly (initiation phase) and later monthly (continuation phase) home visits to verify treatment adherence, screen household contacts for TB, and assess IPT uptake in children under five. Among 359 enrolled TB patients, 237 (66.0%) were male, and 37 (10.3%) were HIV-positive. Three hundred forty (94.7%) participants had treatment success, seven (1.9%) died, seven (1.9%) experienced treatment failure, and five (1.4%) were lost-to-follow-up. Among 1585 household contacts screened for TB, 26 (1.6%) had TB symptoms, of whom five (19.2%) were diagnosed with pulmonary TB. IPT referral was done for 376 children from 198 households. In a challenging setting, where DOT is often not feasible, CS-SAT led to successful TB treatment outcomes and created an opportunity for active TB case finding and IPT referral. We recommend the Guinean CS-SAT model for implementation in similar settings.

Impact of randomized blinded rechecking program on the performance of the AFB Microscopy Laboratory Network in Uganda: a decadal retrospective study

BackgroundSmear microscopy has remained the initial diagnostic test for presumptive tuberculosis (TB) patients in health facilities without the World Health Organization (WHO) recommended rapid diagnostic tools. In the Uganda TB laboratory network, the technique remains the only tool to monitor response to treatment among drug susceptible TB patients, with the country currently having over 1,600 microscopy TB testing units. It has been evidenced that acid-fast bacilli (AFB) microscopy’s yield highly depends on the staining technique and reading ability of the laboratory personnel. For the quality of TB testing in the country, the TB control program set up a Randomized Blinded Rechecking (RBRC) program in 2008 to monitor the testing performance of laboratories to continuously improve the reliability and efficiency of results. This is the first study to determine the effectiveness and impact of the RBRC program on the performance of the participating laboratories in Uganda.MethodsThis was a retrospective cross-sectional study based on a record review of the RBRC’s annual results compilations between January 2008 and December 2017.ResultsBetween January 2008 and December 2017, a total of 265,523 smears were re-checked during the RBRC program. The number of enrolled laboratories in the RBRC program rose from 660 to 2008 to 1,406 in 2017. The RBRC program resulted in a statistically significant reduction in microscopy errors, with false positives decreasing from 12.8% to 2008 to 7.6% in 2017, false positive errors decreasing from 10 to 6.3%, false negative errors decreasing from 2.9 to 0.7%, quantification errors decreasing from 6.0 to 1.8%, and the overall sensitivity of smear microscopy compared to the controllers increased with statistical significance from 93 to 97%.ConclusionThe study reveals an overall significant error reduction and an improved sensitivity of smear microscopy upon continuous implementation of the RBRC program in an AFB microscopy TB laboratory network. Implementation of a RBRC program is crucial and essential to maintaining a reliable TB laboratory service that can facilitate accurate diagnosis and offset the disadvantages of using smear microscopy.

Optimizing (O) rifapentine-based (RI) regimen and shortening (EN) the treatment of drug-susceptible tuberculosis (T) (ORIENT) using an adaptive seamless design: study protocol of a multicenter randomized controlled trial

BackgroundStandard treatment for drug-susceptible tuberculosis (DS-TB) includes a multidrug regimen requiring at least 6 months of treatment, and this lengthy treatment easily leads to poor adherence. There is an urgent need to simplify and shorten treatment regimens to reduce interruption and adverse event rates, improve compliance, and reduce costs.MethodsORIENT is a multicenter, randomized controlled, open-label, phase II/III, non-inferiority trial involving DS-TB patients to evaluate the safety and efficacy of short-term regimens compared with the standardized six-month treatment regimen. In stage 1, corresponding to a phase II trial, a total of 400 patients are randomly divided into four arms, stratified by site and the presence of lung cavitation. Investigational arms include 3 short-term regimens with rifapentine 10 mg/kg, 15 mg/kg, and 20 mg/kg, while the control arm uses the standardized six-month treatment regimen. A combination of rifapentine, isoniazid, pyrazinamide, and moxifloxacin is administered for 17 or 26 weeks in rifapentine arms, while a 26-week regimen containing rifampicin, isoniazid, pyrazinamide, and ethambutol is applied in the control arm. After the safety and preliminary effectiveness analysis of patients in stage 1, the control arm and the investigational arm meeting the conditions will enter into stage 2, which is equivalent to a phase III trial and will be expanded to recruit DS-TB patients. If all investigational arms do not meet the safety conditions, stage 2 will be canceled. In stage 1, the primary safety endpoint is permanent regimen discontinuation at 8 weeks after the first dose. The primary efficacy endpoint is the proportion of favorable outcomes at 78 weeks after the first dose for both two stages.DiscussionThis trial will contribute to the optimal dose of rifapentine in the Chinese population and suggest the feasibility of the short-course treatment regimen containing high-dose rifapentine and moxifloxacin for DS-TB.Trial registrationThe trial has been registered on ClinicalTrials.gov on 28 May 2022 with the identifier NCT05401071.

Adherence to Tuberculosis Treatment and Its Associated Factors among Drug-susceptible Tuberculosis Patients in Lira District, Northern Uganda

Uganda has a high incidence of tuberculosis infection at 200 cases per 100,000 people. With effective therapy and adherence to medications is essential for reducing the spread of tuberculosis in the community. However, many of the initiated patients do not get to finish the entire course of treatment. The purpose of this study was to investigate the level of and factors associated with tuberculosis treatment adherence among drug-susceptible tuberculosis patients in the Lira district. A facility-based cross-sectional survey was conducted among 234 randomly selected tuberculosis patients between October and December 2022. The Morisky medication adherence scale was used to measure adherence. Using a structured questionnaire to collect data on socio-demographic characteristics, community factors, and health service delivery factors associated with adherence. Binary logistic regression analysis was used to determine the correlates of adherence to tuberculosis drugs at a p value of 0.05. Most of the respondents (135, 57.7%) were males, (93, 39.7%) aged above 45 years, and (135, 57.7%) in a marital relationship. The prevalence of adherence to tuberculosis drugs was 84.6% (198/234) and was associated with marital status (AOR: 0.307; 95% CI: 0.13-0.0724, p=0.007) and the experience of stigma (AOR: 4.39; 95% CI: 1.612-11.958, p=0.004). The study reported that 2 in 10 drug-susceptible tuberculosis patients are non-adherent, which is lower than the targeted 90%. Marital status and stigma experience are predictors of non-adherence. Interventions by the ministry of health should target how to improve tuberculosis treatment and reduce stigma.

Diabetes mellitus is associated with an increased risk of unsuccessful treatment outcomes among drug-susceptible tuberculosis patients in Ethiopia: A prospective health facility-based study

BackgroundThe impact of diabetes mellitus on tuberculosis (TB) treatment outcomes has not been well investigated in most sub-Saharan countries including Ethiopia. The current study aimed to determine the association between diabetes mellitus and unsuccessful TB treatment outcomes among drug-susceptible TB patients treated at selected health facilities in Addis Ababa, Ethiopia. MethodsThis health facility-based prospective cohort study was conducted at six randomly selected public health centers in Addis Ababa, from August 2020 until November 2021. Clinically diagnosed adult pulmonary and extra pulmonary TB patients were recruited at the time of treatment initiation. A multivariable logistic regression analysis was used to estimate the association between diabetes and unsuccessful TB treatment outcomes. ResultsAmong the total 267 enrolled participants, 9.7% of patients with TB were identified to have diabetes comorbidity. Of patients with diabetes and TB, 9 (34.6%) were newly diagnosed based on glucose test results. Despite an overall high TB treatment success rate (94.0%), more than one-fourth (26.9%) of patients with diabetes had a poor TB treatment outcome (26.9%), which was remarkably higher compared to patients without diabetes (3.7%). In multivariable regression, the adjusted odds of poor TB treatment outcome among those with diabetes was 14.8 (95% CI 3.5 – 62.7) times the odds of poor outcome patients without diabetes. ConclusionDiabetes was significantly associated with increased odds of poor TB treatment outcomes among patients in Addis Ababa, Ethiopia.

Quality of life among tuberculosis patients on treatment in Southwest Nigeria

BackgroundTuberculosis is still a major public health concern that affects millions of people worldwide. Despite the fact that tuberculosis has a well-established treatment, little attention is paid to the quality of life of TB patients on treatment. Poor quality of life has been linked to lower treatment adherence in patients having TB. As a result, the purpose of this study was to evaluate the quality of life of tuberculosis patients and its associated factors. MethodsThe study was a cross-sectional study conducted in Southwest Nigeria among drug-susceptible tuberculosis patients between February and September 2020. The World Health Organization Quality of Life Brief version questionnaire was used to collect data on quality of life (WHOQOL-BREF). A total of 330 people were approached. SPSS version 20 was used to analyze the data. The descriptive data was analyzed using means, standard deviations, and proportions, while the Chi-Square test and binary logistic regression were used to assess the association between variables. P < 0.05 was used to determine statistical significance. ResultsThe respondents' average age was 35.50 ± 11.59 years and most of the respondents (67.9%) were males. The overall mean quality of life was good (4.01 ± 0.529) with the highest score (66.47 ± 10.50) in the environmental domain and the least score (62.88 ± 15.36) in the social domain. There was an association between good quality of life and the patient's length of illness prior to diagnosis (AOR = 0.468, 95% CI = 0.225–0.973). ConclusionIn line with this study, the overall quality of life of drug-susceptible tuberculosis patients is good and is related to the duration of illness before the diagnosis of tuberculosis was made. Therefore, more efforts should be made to increase awareness of tuberculosis and intensify active case finding to enhance early case detection and a better quality of life.

Modelling Outcome of Drug Resistant Tuberculosis and Drug Susceptible Tuberculosis Patients in Oyo State

TB is perhaps the most important contagious disease in the world and the leading cause of mortality by an infectious disease. As a result, WHO declared that achieving the reduction in TB incidence rate for achievement of the 90-90-90 target of the END-TB strategy will be an illusion, if something severe is not done. Therefore, it is imperative to assess the visibility of achieving the END-TB goal in the country (Nigeria) by assessing the success of TB treatments so far in the country. Hence, this paper aims to model the outcome of drug-resistant-tuberculosis and drug-susceptible-tuberculosis patients in Oyo state of Nigeria using the logit function of estimating binary logistic regression model vis-à-vis identifying the success of these TB treatments. At baseline, based on WHO categorization, the study revealed the commonest cases of patients receiving DS-TB seen are ‘New’ (90.5%) followed by relapse after failure (4.2%). Contrarily, the commonest cases of patients receiving DR-TB seen are treatment after failure (44.3%), new (27.5%) and relapse after failure cases (20.6%). Four months after starting treatment, 91.5% and 3.2% were reportedly alive and dead respectively for patients receiving DS-TB treatment while 85.3% and 11.5% were reportedly alive and dead respectively for receiving DR-TB treatment. Hence, the percentage success of DS-TB recorded was higher than the recorded for DR-TB patients. Furthermore, the chi-square results for DS-TB patients indicated that mortality significantly associated with DS-TB categorised patients (i.e. Relapse) and HIV status (i.e. Negative). Also, for the DR-TB patients, the results depicted that mortality significantly associated with DR-TB categorised patients (i.e. TAF, Treatment after Loss to Follow Up and New), both HIV status and Sputum Smear status (i.e. Positive). Nevertheless, among other findings, the binary logistic regression model estimations revealed that categorised New patients and Sputum Smear status unfavourably and significantly predicted the treatment outcome (mortality) of DS-TB and DR-TB patients. As well, categorised Relapse patients unfavourably and significantly predicted the treatment outcome (mortality) of DR-TB patients. Thus, the DS-TB method of treatment is recommended in order to achieve the target goal of the END-TB strategy in Oyo state Nigeria.

Journey of the tuberculosis patients in India from onset of symptom till one-year post-treatment.

Historically, economic studies on tuberculosis estimated out-of-pocket expenses related to tuberculosis treatment and catastrophic cost, however, no study has yet been conducted to understand the post-treatment economic conditions of the tuberculosis patients in India. In this paper, we add to this body of knowledge by examining the experiences of the tuberculosis patients from the onset of symptoms till one-year post-treatment. 829 adult drug-susceptible tuberculosis patients from general population and from two high risk groups: urban slum dwellers and tea garden families were interviewed during February 2019 to February 2021 at their intensive and continuation phases of treatment and about one-year post-treatment using adapted World Health Organization tuberculosis patient cost survey instrument. Interviews covered socio-economic conditions, employment status, income, out-of-pocket expenses and time spent for outpatient visits, hospitalization, drug-pick up, medical follow-ups, additional food, coping strategies, treatment outcome, identification of post-treatment symptoms and treatment for post-treatment sequalae/recurrent cases. All costs were calculated in 2020 Indian rupee (INR) and converted into US dollar (US$) (1 US$ = INR 74.132). Total cost of tuberculosis treatment since the onset of symptom till one-year post-treatment ranged from US$359 (Standard Deviation (SD) 744) to US$413 (SD 500) of which 32%-44% of costs incurred in pre-treatment phase and 7% in post-treatment phase. 29%-43% study participants reported having outstanding loan with average amount ranged from US $103 to US$261 during the post-treatment period. 20%-28% participants borrowed during post-treatment period and 7%-16% sold/mortgaged personal belongings. Therefore, economic impact of tuberculosis persists way beyond treatment completion. Major reasons of continued hardship were costs associated with initial tuberculosis treatment, unemployment, and reduced income. Therefore, policy priorities to reduce treatment cost and to protect patients from the economic consequences of the disease by ensuring job security, additional food support, better management of direct benefit transfer and improving coverage through medical insurances need consideration.

Mass spectrometry-based identification of new serum biomarkers in patients with latent infection pulmonary tuberculosis

Noninvasive and simple indicators for diagnosing latent tuberculosis (TB) infection (LTBI) and tracking progression from latent infection to active TB infection are still desperately needed. The aim of this study was to screen and identify possible biomarkers for diagnosing LTBI and monitoring the progression from latent infection to active TB infection, as well as to investigate the underlying processes and functions. To assess changes in metabolite composition associated with active tuberculosis infection in humans, whole blood supernatants were collected from patients with LTBI, drug-susceptible TB patients, drug-resistant TB patients, and healthy controls. The metabolites in all serum samples were extracted by oscillatory, deproteinization, and then detected by liquid chromatography-tandem mass spectrometry/MS analysis. Normalization by Pareto-scaling method, the difference analysis was carried out by Metaboanalyst 4.0 software, and 1-way analysis of variance analysis among groups showed that P-value < 0.05 was regarded as a different metabolite. To clarify the dynamic changes and functions of differential metabolites with disease progression, and explore its significance and mechanism as a marker by further cluster analysis, functional enrichment analysis, and relative content change analysis of differential metabolites. 65 metabolites were substantially different in four groups. Differential metabolites such as Inosine and Prostaglandin E1 may be important blood indicators for diagnosing mycobacterium tuberculosis latent infection, which were all tightly connected to amino acid metabolism, Biosynthesis of various secondary metabolites, Nucleotide metabolism, Endocrine system, Immune system, Lipid metabolism, and Nervous system. This study screened and identified Inosine, 16, 16-dimethyl-6-keto Prostaglandin E1, Theophylline, and Cotinine as potential serum biomarkers for diagnosing latent TB infection, and Cotinine as potential biomarkers for monitoring disease progression from healthy population to LTBI and then to active TB including drug-resistant TB infection and sensitive TB infection. Furthermore, this research provides a preliminary experimental basis to further investigate the development of metabolomics-based diagnosis of LTBI and monitoring the progress from latent infection to active TB infection.

Preventive Treatment for Household Contacts of Drug-Susceptible Tuberculosis Patients.

People who live in the household of someone with infectious pulmonary tuberculosis are at a high risk of tuberculosis infection and subsequent progression to tuberculosis disease. These individuals are prioritized for contact investigation and tuberculosis preventive treatment (TPT). The treatment of TB infection is critical to prevent the progression of infection to disease and is prioritized in household contacts. Despite the availability of TPT, uptake in household contacts is poor. Multiple barriers prevent the optimal implementation of these policies. This manuscript lays out potential next steps for closing the policy-to-implementation gap in household contacts of all ages.

Determinants of Treatment Outcomes among Drug-Susceptible Tuberculosis Patients on Directly Observed Treatment Short-Course at Federal Medical Centre, Abeokuta, South-West, Nigeria

Background: Surveillance of tuberculosis treatment outcomes is very crucial in evaluating successes of tuberculosis (TB) intervention programmes as well as assessing progress towards achieving the Sustainable Development Goals target of ending TB infection by 2030. The study assessed treatment outcomes of tuberculosis and the determinants among tuberculosis patients on Directly Observed Treatment Short-course (DOTs) at Federal Medical Centre, Abeokuta South-West, Nigeria.&#x0D; Methods: This was a retrospective review of treatment outcomes of patients managed for Tuberculosis at the facility between January 2015 and December 2019. Data were retrieved from the treatment register and analysed using IBM® SPSS software version 23. Results were presented using frequencies and percentages, while the Chi-square test was used to test for association between the treatment outcomes and the independent variables. Binary logistics regression was used to assess for determinants of treatment outcomes at a level of significance of p&lt;0.05.&#x0D; Results: A total of 726 records were reviewed. The median age of the patients was 35.0 years (IQR 25). The treatment success rate (TSR) and cure rate were 83.2% and 43.7% respectively. TB patients with negative HIV status were about two times more likely to have successful treatment outcomes (OR=1.86, 95%CI=1.20-2.88).&#x0D; Conclusion: The TSR and cure rate obtained in this study were below the national targets set by the World Health Organization, and HIV co-infection was a threat to successful treatment outcomes among TB patients. Ensuring optimized antiretroviral therapy, prompt diagnosis and treatment of TB in HIV patients will go a long way in improving treatment outcomes.

Hidden loss to follow-up among tuberculosis patients managed by public–private mix institutions in South Korea

In South Korea, public–private mix (PPM) was launched in 2011. This retrospective cohort study sought to determine the rate of loss to follow-up (LTFU) among drug-susceptible tuberculosis (DS-TB) patients in all nationwide PPM institutions, and the risk factors for LTFU. National notification data for DS-TB patients diagnosed between August 2011 and July 2014 in PPM institutions were analysed. Determination of LTFU included detection of instances where patients were transferred out, but when they did not attend at other TB centres in the following two months. Univariable and multivariable competing risk models were used to determine risk factors for LTFU. 73,046 patients with 78,485 records were enrolled. Nominally, 3426 (4.4%) of records were LTFU. However, after linking the multiple records in each patient, the percentage of LTFU was 12.3% (9004/73,046). Risk factors for LTFU were: being foreign-born (3.13 (95% CI 2.77–3.53)), prior LTFU (2.31 (2.06–2.59)) and greater distance between the patient’s home and the TB centre (4.27 (4.03–4.53)). ‘Transfer-out’ was a risk factor in patients managed by treatment centres close to home (1.65 (1.49–1.83)), but protective for those attending centres further (0.77 (0.66–0.89)) or far-away (0.52 (0.46–0.59)) from home. By considering the complete picture of a patient’s interactions with healthcare, we identified a much higher level of LTFU than previously documented. This has implications for how outcomes of treatment are reported and argues for a joined-up national approach for the management and surveillance of TB patients, in nations with similar healthcare systems.

Tuberculostearic Acid-Containing Phosphatidylinositols as Markers of Bacterial Burden in Tuberculosis.

One-fourth of the global human population is estimated to be infected with strains of the Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB). Using lipidomic approaches, we show that tuberculostearic acid (TSA)-containing phosphatidylinositols (PIs) are molecular markers for infection with clinically relevant MTBC strains and signify bacterial burden. For the most abundant lipid marker, detection limits of ∼102 colony forming units (CFUs) and ∼103 CFUs for bacterial and cell culture systems were determined, respectively. We developed a targeted lipid assay, which can be performed within a day including sample preparation—roughly 30-fold faster than in conventional methods based on bacterial culture. This indirect and culture-free detection approach allowed us to determine pathogen loads in infected murine macrophages, human neutrophils, and murine lung tissue. These marker lipids inferred from mycobacterial PIs were found in higher levels in peripheral blood mononuclear cells of TB patients compared to healthy individuals. Moreover, in a small cohort of drug-susceptible TB patients, elevated levels of these molecular markers were detected at the start of therapy and declined upon successful anti-TB treatment. Thus, the concentration of TSA-containing PIs can be used as a correlate for the mycobacterial burden in experimental models and in vitro systems and may prospectively also provide a clinically relevant tool to monitor TB severity.

Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts.

ABSTRACTObjective:To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. Methods:The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. Results:The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. Conclusions:This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.