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2.
Front Immunol ; 13: 870768, 2022.
Article in English | MEDLINE | ID: covidwho-1957155

ABSTRACT

Tuberculosis (TB), considered an ancient disease, is still killing one person every 21 seconds. Diagnosis of Mycobacterium tuberculosis (M.tb) still has many challenges, especially in low and middle-income countries with high burden disease rates. Over the last two decades, the amount of drug-resistant (DR)-TB cases has been increasing, from mono-resistant (mainly for isoniazid or rifampicin resistance) to extremely drug resistant TB. DR-TB is problematic to diagnose and treat, and thus, needs more resources to manage it. Together with+ TB clinical symptoms, phenotypic and genotypic diagnosis of TB includes a series of tests that can be used on different specimens to determine if a person has TB, as well as if the M.tb strain+ causing the disease is drug susceptible or resistant. Here, we review and discuss advantages and disadvantages of phenotypic vs. genotypic drug susceptibility testing for DR-TB, advances in TB immunodiagnostics, and propose a call to improve deployable and low-cost TB diagnostic tests to control the DR-TB burden, especially in light of the increase of the global burden of bacterial antimicrobial resistance, and the potentially long term impact of the coronavirus disease 2019 (COVID-19) disruption on TB programs.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , COVID-19/diagnosis , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/genetics , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/microbiology , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology
4.
Trials ; 23(1): 484, 2022 Jun 13.
Article in English | MEDLINE | ID: covidwho-1885333

ABSTRACT

BACKGROUND: Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9-24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. METHODS: TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. DISCUSSION: TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment. TRIAL REGISTRATION: Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.


Subject(s)
Antitubercular Agents/therapeutic use , Diarylquinolines/therapeutic use , Linezolid/therapeutic use , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Adolescent , Adult , Antibiotics, Antitubercular/pharmacology , Antibiotics, Antitubercular/therapeutic use , Antitubercular Agents/pharmacology , Diarylquinolines/pharmacology , Humans , Linezolid/pharmacology , Pandemics , Rifampin/pharmacology , Treatment Outcome , Tuberculosis, Multidrug-Resistant/diagnosis , Young Adult
5.
7.
BMC Public Health ; 22(1): 976, 2022 05 14.
Article in English | MEDLINE | ID: covidwho-1865290

ABSTRACT

BACKGROUND: Loss to follow-up (LTFU) from tuberculosis (TB) treatment and care is a major public health problem as patients can be infectious and also may develop a multi-drug resistant TB (MDR-TB). The study aimed to assess whether LTFU differs by the distance TB patients travelled to receive care from the nearest health facility. METHODS: A total of 402 patient cards of TB patients who received care were reviewed from March 1-30, 2020. The Kaplan-Meir curve with the Log-rank test was used to compare differences in LTFU by the distance travelled to reach to the nearest health facility for TB care. The Cox proportional hazard regression model was used to identify predictors. All statistical tests are declared significant at a p-value< 0.05. RESULTS: A total of 37 patients were LTFU with the incidence rate of 11.26 per 1000 person-months of observations (PMOs) (95% CI: 8.15-15.53). The incidence rate ratio was 12.19 (95% CI: 5.01-35.73) among the groups compared (those who travelled 10 km or more versus those who travelled less than 10 km). Age ≥ 45 years (aHR = 7.71, 95% CI: 1.72, 34.50), educational status (primary schooling, aHR = 3.54, 95% CI: 1.49, 8.40; secondary schooling, aHR = 2.75, 95% CI: 1.08, 7.03), lack of family support (aHR = 2.80, 95% CI: 1.27, 6.19), nutritional support (aHR = 3.40, 95% CI:1.68, 6.89), ≥ 10 km distance to travel to a health facility (aHR = 6.06, 95% CI: 2.33, 15.81) had significantly predicted LTFU from TB treatment and care. CONCLUSIONS: LTFU from adult TB care and treatment was 12 times higher among those who travelled ≥10 km to reach a health facility compared to those who travelled less. To retain adult TB patients in care and ensure appropriate treatment, health professionals and other stakeholders should give due attention to the factors that drive LTFU. We suggest identifying concerns of older patients at admission and those who travel long distance and establish social support platforms that could help people to complete TB treatment.


Subject(s)
HIV Infections , Tuberculosis, Multidrug-Resistant , Tuberculosis , Adult , Ethiopia/epidemiology , Follow-Up Studies , HIV Infections/epidemiology , Humans , Lost to Follow-Up , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy
9.
CPT Pharmacometrics Syst Pharmacol ; 11(5): 628-639, 2022 05.
Article in English | MEDLINE | ID: covidwho-1858907

ABSTRACT

Bedaquiline (BDQ) is recommended for treatment of multidrug-resistant tuberculosis (MDR-TB) for the majority of patients. Given its long terminal half-life and safety concerns, such as QTc-prolongation, re-introducing BDQ after multiple dose interruption is not intuitive and there are currently no existing guidelines. In this simulation-based study, we investigated different loading dose strategies for BDQ re-introduction, taking safety and efficacy into account. Multiple scenarios of time and length of interruption as well as BDQ re-introduction, including no loading dose, 1- and 2-week loading doses (200 mg and 400 mg once daily), were simulated from a previously published population pharmacokinetic (PK) model describing BDQ and its main metabolite M2 PK in patients with MDR-TB. The efficacy target was defined as 95.0% of the average BDQ concentration without dose interruption during standard treatment. Because M2 is the main driver for QTc-prolongation, the safety limit was set to be below the maximal average M2 metabolite concentration in a standard treatment. Simulations suggest that dose interruptions between treatment weeks 3 and 72 (interruption length: 1 to 6 weeks) require a 2-week loading dose of 200 mg once daily in the typical patient. If treatment was interrupted for longer than 8 weeks, a 2-week loading dose (400 mg once daily) was needed to reach the proposed efficacy target, slightly exceeding the safety limit. In conclusion, we here propose a strategy for BDQ re-introduction providing guidance to clinicians for safe and efficacious BDQ dosing.


Subject(s)
Long QT Syndrome , Tuberculosis, Multidrug-Resistant , Antitubercular Agents , Diarylquinolines/pharmacokinetics , Humans , Tuberculosis, Multidrug-Resistant/drug therapy
10.
Lancet Infect Dis ; 22(4): 496-506, 2022 04.
Article in English | MEDLINE | ID: covidwho-1839428

ABSTRACT

BACKGROUND: Bedaquiline improves outcomes of patients with rifampicin-resistant and multidrug-resistant (MDR) tuberculosis; however, emerging resistance threatens this success. We did a cross-sectional and longitudinal analysis evaluating the epidemiology, genetic basis, and treatment outcomes associated with bedaquiline resistance, using data from South Africa (2015-19). METHODS: Patients with drug-resistant tuberculosis starting bedaquiline-based treatment had surveillance samples submitted at baseline, month 2, and month 6, along with demographic information. Culture-positive baseline and post-baseline isolates had phenotypic resistance determined. Eligible patients were aged 12 years or older with a positive culture sample at baseline or, if the sample was invalid or negative, a sample within 30 days of the baseline sample submitted for bedaquiline drug susceptibility testing. For the longitudinal study, the first surveillance sample had to be phenotypically susceptible to bedaquiline for inclusion. Whole-genome sequencing was done on bedaquiline-resistant isolates and a subset of bedaquiline-susceptible isolates. The National Institute for Communicable Diseases tuberculosis reference laboratory, and national tuberculosis surveillance databases were matched to the Electronic Drug-Resistant Tuberculosis Register. We assessed baseline resistance prevalence, mutations, transmission, cumulative resistance incidence, and odds ratios (ORs) associating risk factors for resistance with patient outcomes. FINDINGS: Between Jan 1, 2015, and July 31, 2019, 8041 patients had surveillance samples submitted, of whom 2023 were included in the cross-sectional analysis and 695 in the longitudinal analysis. Baseline bedaquiline resistance prevalence was 3·8% (76 of 2023 patients; 95% CI 2·9-4·6), and it was associated with previous exposure to bedaquiline or clofazimine (OR 7·1, 95% CI 2·3-21·9) and with rifampicin-resistant or MDR tuberculosis with additional resistance to either fluoroquinolones or injectable drugs (pre-extensively-drug resistant [XDR] tuberculosis: 4·2, 1·7-10·5) or to both (XDR tuberculosis: 4·8, 2·0-11·7). Rv0678 mutations were the sole genetic basis of phenotypic resistance. Baseline resistance could be attributed to previous bedaquiline or clofazimine exposure in four (5·3%) of 76 patients and to primary transmission in six (7·9%). Odds of successful treatment outcomes were lower in patients with baseline bedaquiline resistance (0·5, 0·3-1). Resistance during treatment developed in 16 (2·3%) of 695 patients, at a median of 90 days (IQR 62-195), with 12 of these 16 having pre-XDR or XDR. INTERPRETATION: Bedaquiline resistance was associated with poorer treatment outcomes. Rapid assessment of bedaquiline resistance, especially when patients were previously exposed to bedaquiline or clofazimine, should be prioritised at baseline or if patients remain culture-positive after 2 months of treatment. Preventing resistance by use of novel combination therapies, current treatment optimisation, and patient support is essential. FUNDING: National Institute for Communicable Diseases of South Africa.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Clofazimine/therapeutic use , Cross-Sectional Studies , Diarylquinolines/therapeutic use , Humans , Longitudinal Studies , Microbial Sensitivity Tests , Mycobacterium tuberculosis/genetics , Rifampin/pharmacology , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
11.
Int J Infect Dis ; 118: 264-269, 2022 May.
Article in English | MEDLINE | ID: covidwho-1838867

ABSTRACT

OBJECTIVES: The study aimed to explore the efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis. METHODS: The randomized controlled study included 50 Mycobacterium tuberculosis culture or pathological-confirmed multidrug resistant tuberculosis patients who received spinal surgery from January 2018 to February 2020. Twenty-five patients were assigned to the control group and the study group, respectively. Random number method was used for patient allocation and they were treated with levofloxacin, pyrazinamide, thioisonicotinamide enteric-coated tablet, amikacin sulfate injection, and sodium p-amino salicylate injection, accompanied by linezolid or not. RESULTS: The overall effective rate of the study group was higher than that of the control group (88.00% vs 64.00%, P<0.05). The severity of pain at 3 and 6 months postoperatively was lower in the study group than that in the control group (P<0.05). Postoperatively, the study group had higher bone graft fusion rate, shorter mean bone graft fusion time, and higher paraspinal cyst absorption rate than the control group (P<0.05). Postoperatively, the study group had lower levels of PCT, ESR, and CRP than the control group (P <0.05). All patients had normal hepatic and renal function, and no statistical difference of adverse effects between 2 groups were found. CONCLUSIONS: Linezolid-based chemotherapeutic regimens can effectively treat patients with postoperative multidrug-resistant spinal tuberculosis but have higher rates of adverse reactions.


Subject(s)
Linezolid , Tuberculosis, Multidrug-Resistant , Tuberculosis, Spinal , Humans , Linezolid/adverse effects , Mycobacterium tuberculosis/drug effects , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/surgery , Tuberculosis, Spinal/drug therapy , Tuberculosis, Spinal/surgery
12.
J Bras Pneumol ; 48(2): e20210515, 2022.
Article in English, Portuguese | MEDLINE | ID: covidwho-1836603

ABSTRACT

OBJECTIVE: 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.


Subject(s)
Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Tuberculosis , Brazil/epidemiology , Humans , Lung , Mexico/epidemiology , Oxygen , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/epidemiology
13.
Front Public Health ; 10: 848370, 2022.
Article in English | MEDLINE | ID: covidwho-1818026

ABSTRACT

In the future, tuberculosis (TB) will place a heavy burden on the aging population in Korea. To prepare for this crisis, it is important to analyze the disease burden trend of drug-susceptible tuberculosis (DS-TB) and multidrug-resistant tuberculosis (MDR-TB). Measuring disability-adjusted life years (DALYs) and economic burden on MDR-TB patients can help reduce the incidence of TB. Accordingly, in this study, we measured the DALYs and economic burden on DS-TB and MDR-TB patients in 2014-2017 using a combination of National Health Insurance claims data, Annual Report on the Notified TB data, and Statistics Korea's mortality data. The incidence-based DALY approach implemented involved the summation of years of life lost and years lived with disability. For measuring economic burden, direct and indirect costs incurred by patients were totaled. From 2014 to 2017, DALYs per 100,000 people with DS-TB were 56, 49, 46, and 40, respectively, and DALYs per 100,000 people with MDR-TB were 3, 2, 2, and 2, respectively. The economic burden for the DS-TB population from 2014 to 2017 was $143.89 million, $136.36 million, $122.85 million, and $116.62 million, respectively, while that for MDR-TB was $413.44 million, $380.25 million, $376.46 million and $408.14 million, respectively. The results showed a decreasing trend in DALYs and economic burden for DS-TB, whereas MDR-TB was still found to be burdensome without a specific trend. With respect to age, the economic burden for both DS-TB and MDR-TB was higher among men than among women till ≤ 79 years. Conversely, the economic burden for women aged ≥80 years was higher as compared to their male counterparts. In conclusion, the incidence and spread of TB in all areas of society must be suppressed through intensive management of MDR-TB in the older population. We hope that the national TB management project will proceed efficiently when the infectious disease management system is biased to one side due to the COVID-19 pandemic.


Subject(s)
COVID-19 , Tuberculosis, Multidrug-Resistant , Tuberculosis , Aged , Cost of Illness , Disability-Adjusted Life Years , Female , Financial Stress , Humans , Male , Pandemics , Tuberculosis/epidemiology , Tuberculosis, Multidrug-Resistant/epidemiology
14.
BMC Infect Dis ; 22(1): 204, 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1779608

ABSTRACT

BACKGROUND: There was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients. METHODS: This retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan-Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47-3.53), than those who did not (median: 10 months, 95% CI: 5.24-14.76) (p-value < 0.001, Log-rank test). Patient's age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7-50.2), 69.9% (95%CI: 61.7-77.2) and 84.9% (95%CI: 78.1-90.3), specificities were respectively, 82.8% (95%CI: 76.9-87.6), 74.6% (95%CI: 68.2-80.4) and 69.4% (95%CI: 62.6-75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7-70.8), 72.7% (95%CI: 67.7-77.2) and 75.8% (95%CI: 71.0-80.1). CONCLUSION: In forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.


Subject(s)
Extensively Drug-Resistant Tuberculosis , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis, Pulmonary , Adult , Antitubercular Agents/therapeutic use , Extensively Drug-Resistant Tuberculosis/diagnosis , Extensively Drug-Resistant Tuberculosis/drug therapy , Humans , Prognosis , Retrospective Studies , Sputum , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
15.
Lancet Glob Health ; 10(4): e543-e554, 2022 04.
Article in English | MEDLINE | ID: covidwho-1778530

ABSTRACT

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a global health emergency. We aimed to evaluate treatment outcomes among people with MDR-TB in Sierra Leone and investigate social and health factors associated with adverse treatment outcomes. METHODS: This national, retrospective cohort study recruited all people notified with MDR-TB to the Sierra Leone National TB Programme, admitted to Lakka hospital (Lakka, Western Area Rural District, Freetown, Sierra Leone) between April, 2017, and September, 2019. Participants were followed up to May, 2021. People who were eligible but had no social or health data available, or were subsequently found to have been misdiagnosed, were excluded from participation. MDR-TB treatment was with the 2017 WHO-recommended short (9-11 month) or long (18-24 month) aminoglycoside-containing regimens. Multivariable logistic regression models examined associations of programmatic social and health data with WHO-defined adverse treatment outcomes (death, treatment failure, loss to follow-up). FINDINGS: Of 370 notified MDR-TB cases, 365 (99%) were eligible for study participation (five participants were excluded due to lack of social or health data or misdiagnosis). Treatment was started by 341 (93%) of 365 participants (317 received the short regimen, 24 received the long regimen, and 24 received no treatment). Median age was 35 years (IQR 26-45), 263 (72%) of 365 were male and 102 (28%) were female, 71 (19%) were HIV-positive, and 127 (35%) were severely underweight (body-mass index <16·5 kg/m2). Overall, 267 (73%) of 365 participants had treatment success, 95 (26%) had an adverse outcome, and three (1%) were still on treatment in May, 2021. Age 45-64 years (adjusted odds ratio [aOR] 2·4, 95% CI 1·2-5·0), severe underweight (aOR 4·2, 1·9-9·3), untreated HIV (aOR 10, 2·6-40·0), chronic lung disease (aOR 2·0, 1·0-4·2), previously unsuccessful drug-sensitive tuberculosis retreatment (aOR 4·3, 1·0-19), and a long regimen (aOR 6·5, 2·3-18·0) were associated with adverse outcomes. A sensitivity analysis showed that prothionamide resistance (aOR 3·1, 95% CI 1·5-10·0) and aminoglycoside-related complete deafness (aOR 6·6, 1·3-35) were independently associated with adverse outcomes. INTERPRETATION: MDR-TB treatment success in Sierra Leone approached WHO targets and the short regimen was associated with higher success. The social and health factors associated with adverse outcomes in this study suggest a role for integrated tuberculosis, HIV, and non-communicable disease services alongside nutritional and socioeconomic support for people with MDR-TB and emphasise the urgent need to scale up coverage of all-oral aminoglycoside-sparing regimens. FUNDING: Wellcome Trust, Joint Global Health Trials.


Subject(s)
HIV Infections , Tuberculosis, Multidrug-Resistant , Tuberculosis , Adult , Aminoglycosides , Antitubercular Agents/therapeutic use , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Sierra Leone/epidemiology , Thinness , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
16.
S Afr J Commun Disord ; 69(1): e1-e13, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1776408

ABSTRACT

BACKGROUND:  South Africa has a high burden of drug-resistant tuberculosis (DRTB) and until recently, ototoxic aminoglycosides were predominant in treatment regimens. Community-based ototoxicity monitoring programmes (OMPs) have been implemented for early detection of hearing loss and increased patient access. OBJECTIVES:  A longitudinal study was conducted to describe the service delivery characteristics of a community-based OMP for DRTB patients facilitated by CHWs as well as observed ototoxic hearing loss in this population. METHOD:  A descriptive retrospective record review of longitudinal ototoxicity monitoring of 194 DRTB patients undergoing treatment at community-based clinics in the city of Cape Town between 2013 and 2017. RESULTS:  Follow-up rates between consecutive monitoring assessments reached as high as 80.6% for patients assessed by CHWs. Few patients (14.2% - 32.6%) were assessed with the regularity (≥ 6 assessments) and frequency required for effective ototoxicity monitoring, with assessments conducted, on average, every 53.4-64.3 days. Following DRTB treatment, 51.5% of patients presented with a significant ototoxic shift meeting one or more of the American Speech-Language-Hearing Association (ASHA) criteria. Deterioration in hearing thresholds was bilateral and most pronounced at high frequencies (4 kHz - 8 kHz). The presence of pre-existing hearing loss, human immunodeficiency virus co-infection and a history of noise exposure were significant predictors of ototoxicity in patients. CONCLUSION:  DRTB treatment with kanamycin resulted in significant deterioration of hearing longitudinally, predominantly at high frequencies. With ongoing training and supportive supervision, CHWs can facilitate community-based ototoxicity monitoring of DRTB patients. Current protocols and guidelines may require reassessment for appropriate community-based ototoxicity monitoring.


Subject(s)
Hearing Loss , Ototoxicity , Tuberculosis, Multidrug-Resistant , Hearing Loss/chemically induced , Hearing Loss/diagnosis , Hearing Loss/epidemiology , Humans , Longitudinal Studies , Ototoxicity/etiology , Retrospective Studies , South Africa , Tuberculosis, Multidrug-Resistant/drug therapy
17.
Front Public Health ; 9: 736632, 2021.
Article in English | MEDLINE | ID: covidwho-1775881

ABSTRACT

To evaluate China's current rifampin-resistant tuberculosis (RR-TB) screening strategy from stakeholders' perspectives, the perceptions, attitudes, and interests of 245 stakeholders from three eastern, central, and western China provinces on RR-TB screening strategies, were investigated through stakeholder survey and interview. The attitudes toward three RR-TB screening strategies were statistically different: inclination to choose who to screen (Z = 98.477; P < 0.001), funding for rapid diagnostic technology screening either by reimbursed health insurance or directly subsidized financial assistance (Z = 4.142, P < 0.001), and respondents' attitude during RR-TB screening implementation levels (Z = 2.380, P = 0.017). In conclusion, RR-TB screening scope could be expanded by applying rapid diagnostic technologies. Provinces with different economic status could adjust their screening policies accordingly.


Subject(s)
Tuberculosis, Multidrug-Resistant , Tuberculosis , Humans , Mass Screening , Rifampin/therapeutic use , Tuberculosis/diagnosis , Tuberculosis/prevention & control , Tuberculosis, Multidrug-Resistant/diagnosis
18.
Eur J Med Chem ; 232: 114173, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1757297

ABSTRACT

Today, tuberculosis (TB) caused by the acid-fast bacilli, Mycobacterium tuberculosis (Mtb) is the most infectious killer disease globally with high morbidity and mortality rates. The rapid development of multi-drug-resistant (MDR) strains via intrinsic (efflux pumps) and acquired (biological mutations) mechanisms reduce the efficacy of applied anti-TB regimens. Nevertheless, only bedaquiline (BDQ) and pretomanid (PMD) were added to anti-TB therapy in the last decade. The existing anti-TB drugs also exhibited cytotoxicity and hepatotoxicity from long-term treatment. Thus, exploring or developing potential and less toxic anti-TB candidates, preferably natural-based candidates, is the call of the day. At present, 'quinoline' could be considered one of the versatile scaffolds presented in most mainstream medicines from comprehensive drug reports. Notably, BDQ with two clinically evaluating anti-TB candidates, TBJA-587 and DC-159a was motivated for utilizing quinoline heterocycles. Accordingly, we have selected 65 natural quinoline heterocycles bearing potential anti-TB agents (40 plant-derived and 25 marine-derived) within MIC value ≤ 50 µg/mL from an extensive literature search. Briefly, source, drug chemistry, structural activity relationship, prior pharmacokinetics profiles with drug-ability, toxicity, and hierarchical clustering analysis using various computational tools to identify the most 'drug-able lead' candidate is the uniqueness of the review. From extensive drug analysis, tetrandrine, 2'-nortiliacorinine, tiliacorine, globospiramine, evocarpine, allocuspareine from plant sources, and ecteinascidin 770, 6-hydroxymanzamine E, (-)-8-hydroxymanzamine A, ecteinascidin 786, manzamine F from marine sources are the most potential-cum-drug-able anti-TB candidates. We hope the systematic and critical drug analyses on quinoline-bearing natural anti-TB candidates are helpful to design potential-cum-less toxic anti-TB drugs in the future.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Antitubercular Agents/chemistry , Humans , Tuberculosis/drug therapy , Tuberculosis, Multidrug-Resistant/drug therapy
20.
Medicina (Kaunas) ; 58(2)2022 Jan 26.
Article in English | MEDLINE | ID: covidwho-1715540

ABSTRACT

Multidrug-resistant (MDR) tuberculosis (TB), resistant to isoniazid and rifampicin, continues to be one of the most important threats to controlling the TB epidemic. Over the last few years, there have been promising pharmacological advances in the paradigm of MDR TB treatment: new and repurposed drugs have shown excellent bactericidal and sterilizing activity against Mycobacterium tuberculosis and several all-oral short regimens to treat MDR TB have shown promising results. The purpose of this comprehensive review is to summarize the most important drugs currently used to treat MDR TB, the recommended regimens to treat MDR TB, and we also summarize new insights into the treatment of patients with MDR TB.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Humans , Isoniazid/therapeutic use , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiology
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