Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study

SummaryBackgroundData from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes.MethodsIn a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes—mortality and culture conversion.Findings195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0·13). Treatment with moxifloxacin (hazard ratio 0·11, 95% CI 0·01–0·82; p=0·03), previous culture-proven multidrug-resistant tuberculosis (5·21, 1·93–14·1; p=0·001), and number of drugs used in a regimen (0·59, 0·45–0·78, p<0·0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0·38, 0·18–0·80; p=0·01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment.InterpretationIn South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity.FundingSouth African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership

Is Universal Screening Necessary? Incidence of Tuberculosis among Tibetan Refugees Arriving in Calgary, Alberta

Background. Canadian policy requires refugees with a history of tuberculosis (TB) or abnormal chest radiograph to be screened after arrival for TB. However, Tibetan refugees are indiscriminately screened, regardless of preimmigration assessment. We sought to determine the incidence of latent (LTBI) and active TB, as well as treatment-related outcomes and associations between preimmigration factors and TB infection among Tibetan refugees arriving in Calgary, Alberta. Design. Retrospective cohort study including Tibetan refugees arriving between 2014 and 2016. Associations between preimmigration factors and incidence of latent and active TB were determined using Chi-square tests. Results. Out of 180 subjects, 49 percent had LTBI. LTBI was more common in migrants 30 years of age or older (). Treatment initiation and completion rates were high at 90 percent and 76 percent, respectively. No associations between preimmigration factors and treatment completion were found. A case of active TB was detected and treated. Conclusion. Within this cohort, the case of active TB would have been detected through the usual postsurveillance process due to a history of TB and abnormal chest radiograph. Forty-nine percent had LTBI, compared to previously quoted rates of 97 percent. Tibetan refugees should be screened for TB in a similar manner to other refugees resettling in Canada.Peer Reviewe

Is Universal Screening Necessary? Incidence of Tuberculosis among Tibetan Refugees Arriving in Calgary, Alberta

Background. Canadian policy requires refugees with a history of tuberculosis (TB) or abnormal chest radiograph to be screened after arrival for TB. However, Tibetan refugees are indiscriminately screened, regardless of preimmigration assessment. We sought to determine the incidence of latent (LTBI) and active TB, as well as treatment-related outcomes and associations between preimmigration factors and TB infection among Tibetan refugees arriving in Calgary, Alberta. Design. Retrospective cohort study including Tibetan refugees arriving between 2014 and 2016. Associations between preimmigration factors and incidence of latent and active TB were determined using Chi-square tests. Results. Out of 180 subjects, 49 percent had LTBI. LTBI was more common in migrants 30 years of age or older (P=0.009). Treatment initiation and completion rates were high at 90 percent and 76 percent, respectively. No associations between preimmigration factors and treatment completion were found. A case of active TB was detected and treated. Conclusion. Within this cohort, the case of active TB would have been detected through the usual postsurveillance process due to a history of TB and abnormal chest radiograph. Forty-nine percent had LTBI, compared to previously quoted rates of 97 percent. Tibetan refugees should be screened for TB in a similar manner to other refugees resettling in Canada

An Evaluation of Procedural Training in Canadian Respirology Fellowship Programs: Program Directors’ and Fellows’ Perspectives

BACKGROUND: In recent years, there has been a rapid growth in diagnostic and therapeutic procedures performed by respirologists.OBJECTIVES: To assess the number and type of procedures performed in Canadian respirology training programs, for comparison with the American College of Chest Physicians minimum competency guidelines, and to assess fellow satisfaction with procedural training during their fellowships.METHODS: Internet-based surveys of Canadian respirology fellows and respirology fellowship program directors were conducted.RESULTS: Response rates for program director and respirology fellow surveys were 71% (10 of 14) and 62% (41 of 66), respectively. Thirty-eight per cent of respirology fellows reported the presence of an interventional pulmonologist at their institution. Flexible bronchoscopy was the only procedure reported by a large majority of respirology fellows (79.5%) to meet American College of Chest Physicians recommendations (100 procedures). As reported by respirology fellows, recommended numbers of procedures were met by 59.5% of fellows for tube thoracostomy, 21% for transbronchial needle aspiration and 5.4% for closed pleural biopsy. Respirology fellows in programs with an interventional pulmonologist were more likely to have completed some form of additional interventional bronchoscopy training (80% versus 32%; P=0.003), had increased exposure to and expressed improved satisfaction with training in advanced diagnostic and therapeutic procedures, but did not increase their likelihood of achieving recommended numbers for any procedures.CONCLUSIONS: Canadian respirology fellows perform lower numbers of basic respiratory procedures, other than flexible bronchoscopy, than that suggested by the American College of Chest Physicians guidelines. Exposure and training in advanced diagnostic and therapeutic procedures is minimal. A concerted effort to improve procedural training is required to improve these results.Peer Reviewe

An evaluation of procedural training in Canadian respirology fellowship programs: Program directors’ and fellows’ perspectives

BACKGROUND: In recent years, there has been a rapid growth in diagnostic and therapeutic procedures performed by respirologists

New treatment options for multidrug-resistant tuberculosis

Despite the development of effective treatments, tuberculosis (TB) remains a major health problem. TB continues to infect new victims and kills nearly 2 million people annually. The problem is much greater in resource-limited countries but is present worldwide. Inadequate public health resources, cost, the obligatory long treatment period, and adverse drug effects contribute to treatment failures and relapses. Drug-resistant Mycobacterium tuberculosis (MTB) strains arise spontaneously and are propagated by inadequate treatment. According to World Health Organization global data, 17% of MTB strains in new, previously untreated cases are resistant to at least one drug. Approximately, 3.3% of new MTB cases are resistant to both isoniazid and rifampin, also called multidrug resistant (MDR), and rates of MDR-TB are greater than 60% in previously treated patients in some countries. Approximately 5% of cases of MDR-TB are also resistant to fluoroquinolones and to injectable drugs, and are called extensively drug resistant (XDR). Recently, XDR strains have been isolated that are also resistant to all standard second-line anti-TB medications. Successful drug treatment of TB with complex resistance profiles is virtually impossible with currently available drugs. There is a desperate need for new compounds that cure strains resistant to currently available drugs and for drugs that are better tolerated and will shorten treatment regimens. In the short term, new strategies for the management of drug-resistant TB with currently available drugs are being explored. These include the use of high-dose isoniazid, substitution of rifabutin in a small proportion of rifampin-resistant cases, linezolid, fluoroquinolones, and phenothiazines. A number of novel drugs are undergoing clinical testing and will hopefully be available in the near future. These include the newer oxazolidinones, diarylquinolines, nitroimidazopyrans, ethenylenediamines, pyrroles, and benzothiazinones

Program-wide review and follow-up of erythema Induratum of Bazin and tuberculosis-associated ocular inflammation management in a TB low-incidence setting: need for improved treatment candidate selection, therapy standardization, and care collaboration

Abstract Background Erythema induratum of Bazin (EIB) – nodular vasculitis associated with Mycobacterium tuberculosis (TB) – and Tuberculosis-Associated Ocular Inflammation (TB-AOI) represent uncommon manifestations of TB. There is limited data and a lack of diagnostic and treatment standards for these conditions. Methods Eleven-year retrospective review of EIB and TB-AOI cases managed in a provincial TB program with prospective phone-based follow-up of anti-tubercular therapy (ATT) recipients. Presumptive TB-AOI and EIB diagnoses were determined by ophthalmologist or dermatologist assessments correlated with positive tuberculin skin test and/or QuantiFERON-TB Gold, along with pathologic criteria in EIB cases. Results Of 21 EIB and 20 TB-AOI cases that received ATT, 13 and 11, respectively, were reached for follow-up. The majority of EIB and TB-AOI cases were female and immigrated from TB high-burden countries. Median durations of pre-diagnosis symptoms were 2 and 0.8 years (IQR 2.5 & 1.1) for EIB and TB-AOI cases, respectively. Overall, 14 different ATT regimens were used for a median duration of 6 months (range 5–9). ATT related adverse events resulting in treatment discontinuation occurred in 14% of EIB and 10% of TB-AOI cases. On last follow-up, 76% of EIB and 42% of TB-AOI had improvement or resolution of disease. Conclusion EIB and TB-AOI were uncommon presentations receiving variable therapy. While treatment response was modest for EIB cases, TB-AOI cases had sub-optimal treatment outcomes. The unique diagnostic and management challenges presented by these conditions in TB low-incidence settings highlight a need for improved treatment candidate selection, therapy standardization, and cross-specialty medical collaboration

Management of Drug Toxicity in Mycobacterium avium Complex Pulmonary Disease: An Expert Panel Survey

Adverse events are frequent in nontuberculous mycobacteria pulmonary disease treatment, but evidence to support their management is scarce. An expert panel survey on management of adverse events shows consistent opinions on management of hepatoxicity, ocular toxicity, ototoxicity, tinnitus, and gastrointestinal upset. These opinions can provide assistance in individual patient management decisions