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1.
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
2.
Int J Tuberc Lung Dis ; 26(7): 650-657, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1912009

ABSTRACT

BACKGROUND: Isoniazid preventive therapy (IPT) for child contacts of TB patients, a globally accepted intervention, needs to be evaluated in diverse geographical regions.OBJECTIVES: To assess the extent of IPT coverage and adherence, to ascertain its sociodemographic and programmatic correlates and to explore existing constraints from service providers and beneficiaries´ perspectives.METHODS: A mixed-method study was conducted in January-June 2021 in Paschim Bardhaman District, West Bengal, India. Quantitative assessment was done among 280 child contacts of TB cases registered between January and December 2020 in all TB units in the district. Primary caregivers were interviewed using a pre-designed questionnaire. Two focus group discussions with all senior treatment supervisors of the district and in-depth interviews with 12 purposively selected caregivers of the children were undertaken. Qualitative data were analysed thematically.RESULTS: Only 48.9% (137/280) of child contacts were screened; 58.9% (165/280) were initiated on IPT and 40% (66/165) adhered to a full course. Coverage of the full 6-month IPT among total study participants was 23.6% (66/280). Household visits by health personnel and initial screening significantly predicted increased coverage. Programmatic inadequacies, poor understanding, social stigma and COVID situation were major constraints.CONCLUSION: Coverage of IPT remains unacceptably low and requires health system strengthening for effectively implementing current recommendations of TB preventive treatment.


Subject(s)
COVID-19 , HIV Infections , Antitubercular Agents/therapeutic use , Child , Family Characteristics , HIV Infections/drug therapy , Health Personnel , Humans , Isoniazid/therapeutic use
3.
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
4.
6.
J Med Chem ; 65(11): 7489-7531, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1864721

ABSTRACT

Over the past 2000 years, tuberculosis (TB) has claimed more lives than any other infectious disease. In 2020 alone, TB was responsible for 1.5 million deaths worldwide, comparable to the 1.8 million deaths caused by COVID-19. The World Health Organization has stated that new TB drugs must be developed to end this pandemic. After decades of neglect in this field, a renaissance era of TB drug discovery has arrived, in which many novel candidates have entered clinical trials. However, while hundreds of molecules are reported annually as promising anti-TB agents, very few successfully progress to clinical development. In this Perspective, we critically review those anti-TB compounds published in the last 6 years that demonstrate good in vivo efficacy against Mycobacterium tuberculosis. Additionally, we highlight the main challenges and strategies for developing new TB drugs and the current global pipeline of drug candidates in clinical studies to foment fresh research perspectives.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , COVID-19/drug therapy , Drug Discovery , Humans , Tuberculosis/drug therapy
8.
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
9.
Immunobiology ; 227(3): 152224, 2022 05.
Article in English | MEDLINE | ID: covidwho-1819510

ABSTRACT

The COVID-19 pandemic has set back progress made on antimicrobial resistance (AMR). Without urgent re-focus, we risk slowing down drug discovery and providing treatment for drug resistant Mycobacterium tuberculosis. Unique in its immune evasion, dormancy and resuscitation, the causal pathogens of tuberculosis (TB) have demonstrated resistance to antibiotics with efflux pumps and the ability to form biofilms. Repurposing drugs is a prospective avenue for finding new anti-TB drugs. There are many advantages to discovering novel targets of an existing drug, as the pharmacokinetic and pharmacodynamic properties have already been established, they are cost-efficient and can be commercially accelerated for the new development. One such group of drugs are non-steroidal anti-inflammatory drugs (NSAIDs) that are originally known for their ability to supress the host proinflammatory responses. In addition to their anti-inflammatory properties, some NSAIDs have been discovered to have antimicrobial modes of action. Of particular interest is Carprofen, identified to inhibit the efflux mechanism and disrupt biofilm formation in mycobacteria. Due to the complexities of host-pathogens interactions in the lung microbiome, inflammatory responses must carefully be controlled alongside the in vivo actions of the prospective anti-infectives. This critical review explores the potential dual role of a selection of NSAIDs, as an anti-inflammatory and anti-tubercular adjunct to reverse the tide of antimicrobial resistance in existing treatments.


Subject(s)
Anti-Infective Agents , COVID-19 , Mycobacterium tuberculosis , Tuberculosis , Anti-Infective Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , COVID-19/drug therapy , Humans , Immunomodulating Agents , Pandemics , Tuberculosis/drug therapy
10.
BMC Infect Dis ; 22(1): 201, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1779609

ABSTRACT

BACKGROUND: China is one of 30 countries with a high tuberculosis (TB) burden, and poor adherence to TB treatment is one of the biggest challenges for TB control. We aimed to explore the barriers and facilitators of treatment adherence among drug-sensitive tuberculosis (DS-TB) patients under the "Integrated model" in Western China, to provide evidence-based treatment and control regimens for DS-TB patients to improve adherence behaviours. METHODS: Both qualitative and quantitative research methods were used to explore the factors associated with self-reported adherence (SRA) behaviours. Questionnaire surveys with DS-TB patients and in-depth interviews with leaders from the Centers for Disease Control and Prevention (CDC) and community health sectors (CHCs), healthcare workers (HCWs) from CHCs, and DS-TB patients were conducted. RESULTS: A total of 459 eligible patients were included in the quantitative survey, and two patients and 13 healthcare providers were included in the in-depth interviews. The percentage of patients who experienced a missed dose, lack of follow-up sputum examination, and interrupted treatment were 19.0%, 11.3%, and 9.2%, respectively. Patients aged 20-39 had a higher risk of missed dose [OR (95% CI): 2.302 (1.001-5.305)] and a lower risk of interrupted treatment [OR (95% CI): 0.278 (0.077-0.982)] than patients more than 60 years. Patients who were of Han ethnicity (OR [95% CI]: 0.524 [0.301-0.912]) received psychological support (OR [95% CI]: 0.379 [0.144-0.998]) from their family and had a lower risk of missed doses. Patients who had drug side effects had a higher risk of interrupted treatment (OR [95% CI]: 2.587 [1.237-5.412]). Patients who possessed higher knowledge had a lower risk of lack of follow-up sputum examination [OR (95% CI): 0.817 (0.673-0.991)]. The results of the qualitative study also reported that patients' poor TB knowledge was the main reason for their non-SRA behaviours. CONCLUSIONS: Patient-centred strategies should be implemented to improve health literacy and strengthen psychological support. More effective case management should be designed and implemented based on different patient characteristics to improve adherence behaviours in further studies.


Subject(s)
Antitubercular Agents , Tuberculosis , Adult , Antitubercular Agents/therapeutic use , China , Humans , Self Report , Surveys and Questionnaires , Tuberculosis/drug therapy , Young Adult
11.
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
12.
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
14.
Genes (Basel) ; 13(3)2022 03 08.
Article in English | MEDLINE | ID: covidwho-1760488

ABSTRACT

Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients' demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1-L4). The two dominating lineages were L4 with 55.8% (n = 215) and L3 with 25.7% (n = 99) of all strains, respectively. Genome-based cluster analysis showed that 30.4% (117/385) of the strains were clustered using a ≤5 single-nucleotide polymorphism (SNP) threshold as a surrogate marker for direct patient-to-patient MTBC transmission. Moreover, 5.2% (20/385) of the strains were multidrug-resistant (MDR), and 50.0% (n = 10) were part of a genome-based cluster (i.e., direct MDR MTBC transmission). Notably, 30.0% (6/20) of the MDR strains were resistant to all first-line drugs and are part of one molecular cluster. Moreover, TB patients in urban living setting had 3.8 times the odds of being infected with a drug-resistant strain as compared to patients from slums (p-value = 0.002). Our results show that L4 strains are the main causative agent of TB in Nairobi and MDR strain transmission is an emerging concern in urban settings. This emphasizes the need for more focused infection control measures and contact tracing of patients with MDR TB to break the transmission chains.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Drug Resistance, Multiple, Bacterial/genetics , Humans , Kenya/epidemiology , Molecular Epidemiology , Mycobacterium tuberculosis/genetics , Poverty Areas , Tuberculosis/epidemiology , Tuberculosis/genetics
15.
Int J Mycobacteriol ; 11(1): 123-125, 2022.
Article in English | MEDLINE | ID: covidwho-1744811

ABSTRACT

Isolated calvarial involvement with tuberculosis (TB) is a very rare entity, with the incidence of only 0.01% of all patients with mycobacterial infections. The factors attributable could be malnutrition, poor socioeconomic conditions, and immunodeficiency syndromes. We hereby present the case of a 35-year-old male who had recently recovered from coronavirus disease 2019 and a diagnosed case of Evan's syndrome with secondary hemophagocytic lymphohistiocytosis who presented with a scalp swelling on the right frontotemporal region. He presented to the emergency department with acute-onset generalized tonic - clonic seizures with high-grade fever. Clinically, the swelling appeared like a cystic swelling of the scalp. On evaluation, there was a collection present below the scalp communicating with the extradural space, involving the underlying skull bone. The patient was operated with drainage of the abscess plus excision of the pathological underlying skull bone. The pus revealed florid amount of acid-fast bacillus on Ziehl-Neelsen staining. The patient was started on four drugs Category 1 antitubercular regimen. The patient responded well to the combined surgical and medical treatment. It should be emphasized that TB can involve any part of the body. It should be kept as differential diagnosis of any chronic inflammatory lesion involving the bony skeleton, especially in endemic countries where combined surgical and medical treatment is usually sufficient to provide a cure.


Subject(s)
COVID-19 , Tuberculosis, Osteoarticular , Adult , Antitubercular Agents/therapeutic use , COVID-19/complications , Diagnosis, Differential , Humans , Male , Skull/diagnostic imaging , Skull/pathology , Skull/surgery , Tuberculosis, Osteoarticular/diagnosis , Tuberculosis, Osteoarticular/drug therapy , Tuberculosis, Osteoarticular/surgery
16.
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
17.
Curr Opin Pulm Med ; 28(3): 211-217, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1713778

ABSTRACT

PURPOSE OF REVIEW: Diagnosis and treatment of drug-resistant tuberculosis (DR-TB) is undergoing substantial changes, owing availability of new diagnostic tools and drugs, coupled with global underdiagnosis and undertreatment. Recent developments are reviewed. RECENT FINDINGS: Molecular diagnostics, for Mycobacterium tuberculosis complex detection and prediction of drug resistance, implemented in the last decade, accelerated TB diagnosis with improved case detection. Nevertheless, access and coverage of drug-resistance testing remain insufficient. Genome sequencing-technologies, based on targeted next-generation sequencing show early potential to mitigate some of the challenges in the future. The recommendation to use an all oral, bedaquiline based regimen for treatment of multidrug-resistant/rifampicin-resistant TB is major advancement in DR-TB care. TB regimen using new and repurposed TB drugs demonstrate in recent clinical trials like, NIX-TB, ZeNIX and TB PRACTECAL considerable treatment success, shorten treatment duration and reduce toxicity. Their optimal use is threatened by the rapid occurrence and spread of strains, resistant to new drugs. Children benefit only very slowly from the progress. SUMMARY: There is notable progress in improved diagnosis and treatment of drug-resistant TB, but complicated by the COVID-19 pandemic the majority of TB patients worldwide don't have (yet) access to the advances.


Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/therapeutic use , Child , Humans , Mycobacterium tuberculosis/genetics , Pandemics , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy
18.
Emerg Infect Dis ; 28(3): 684-692, 2022 03.
Article in English | MEDLINE | ID: covidwho-1705895

ABSTRACT

We evaluated the effects of the coronavirus disease pandemic on diagnosis of and treatment for tuberculosis (TB) in Vietnam. We obtained quarterly notifications for TB and multidrug-resistant/rifampin-resistant (MDR/RR) TB from 2015-2020 and evaluated changes in monthly TB case notifications. We used an interrupted time series to assess the change in notifications and treatment outcomes. Overall, TB case notifications were 8% lower in 2020 than in 2019; MDR/RR TB notifications were 1% lower. TB case notifications decreased by 364 (95% CI -1,236 to 508) notifications per quarter and MDR/RR TB by 1 (95% CI -129 to 132) notification per quarter. The proportion of successful TB treatment outcomes decreased by 0.1% per quarter (95% CI -1.1% to 0.8%) in 2020 compared with previous years. Our study suggests that Vietnam was able to maintain its TB response in 2020, despite the pandemic.


Subject(s)
COVID-19 , Tuberculosis, Multidrug-Resistant , Tuberculosis , Antitubercular Agents/therapeutic use , COVID-19/epidemiology , Humans , Pandemics , Retrospective Studies , SARS-CoV-2 , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Vietnam/epidemiology
20.
PLoS One ; 16(12): e0261329, 2021.
Article in English | MEDLINE | ID: covidwho-1595850

ABSTRACT

BACKGROUND: Rapid and early detection of drug susceptibility among multidrug-resistant tuberculosis (MDR-TB) patients could guide the timely initiation of effective treatment and reduce transmission of drug-resistant TB. In the current study, we evaluated the diagnostic performance of GenoType MTBDRsl (MTBDRsl) ver1.0 assay for detection of resistance to ofloxacin (OFL), kanamycin (KAN) and ethambutol (EMB), and additionally the XDR-TB among MDR-TB patients in Bangladesh. METHODS: The MTBDRsl assay was performed directly on 218 smear-positive sputum specimens collected from MDR-TB patients and the results were compared with the phenotypic drug susceptibility testing (DST) performed on solid Lowenstein-Jensen (L-J) media. We also analyzed the mutation patterns of gyrA, rrs, and embB genes for detection of resistance to OFL, KAN and EMB, respectively. RESULTS: The sensitivity and specificity of the MTBDRsl compared to phenotypic L-J DST were 81.8% (95% CI, 69.1-90.9) and 98.8% (95% CI, 95.6-99.8), respectively for OFL (PPV: 95.7% & NPV: 94.1%); 65.1% (95% CI, 57.5-72.2) and 86.7% (95% CI, 73.2-94.9), respectively for EMB (PPV: 94.9% & NPV: 39.4%); and 100% for KAN. The diagnostic accuracy of KAN, OFL and EMB were 100, 94.5 and 69.6%, respectively. Moreover, the sensitivity, specificity and diagnostic accuracy of MtBDRsl for detection of XDR-TB was 100%. The most frequently observed mutations were at codon D94G (46.8%) of gyrA gene, A1401G (83.3%) of rrs gene, and M306V (41.5%) of the embB gene. CONCLUSION: Considering the excellent performance in this study we suggest that MTBDRsl assay can be used as an initial rapid test for detection of KAN and OFL susceptibility, as well as XDR-TB directly from smear-positive sputum specimens of MDR-TB patients in Bangladesh.


Subject(s)
Mycobacterium tuberculosis/genetics , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/genetics , Adult , Aged , Aged, 80 and over , Antitubercular Agents/therapeutic use , Bangladesh/epidemiology , DNA, Bacterial/genetics , Ethambutol/therapeutic use , Extensively Drug-Resistant Tuberculosis/diagnosis , Extensively Drug-Resistant Tuberculosis/drug therapy , Extensively Drug-Resistant Tuberculosis/genetics , Female , Genotype , Genotyping Techniques/methods , Humans , Kanamycin/therapeutic use , Male , Microbial Sensitivity Tests , Middle Aged , Ofloxacin/therapeutic use , Sensitivity and Specificity , Sputum/chemistry , Tuberculosis, Multidrug-Resistant/drug therapy
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