Management of tuberculosis: are the practices homogeneous in high-income countries?

Objectives: to evaluate and compare practices regarding the diagnosis, isolation measures, and treatment of tuberculosis (TB) in high-income countries and mainly in Europe. Materials and Methods: a survey was conducted from November 2018 to April 2019 within the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). The practices observed were compared to the main international guidelines. Results: among 136 ESGMYC members, 64 (17 countries) responded to the questionnaire. In their practice, two (20.7%) or three sputum samples (79.3%) were collected for the diagnosis of pulmonary TB, alternatively induced sputum (n = 37, 67.2%), bronchoscopy (34, 58.6%), and gastric aspirates (15, 25.9%). Nucleic acid amplification tests (NAATs) were performed by 41 (64%) respondents whatever the smear result and by 47 (73%) in case of smear-positive specimens. NAAT and adenosine deaminase measurement were used for extrapulmonary TB diagnosis in 83.6 and 40.4% of cases, respectively. For isolation duration, 21 respondents (42.9%) were keeping isolation until smear negativity. An initial treatment without ethambutol was offered by 14% (n = 9) of respondents. Corticosteroid therapy, cerebrospinal fluid opening pressure testing, and repeated lumbar puncture were carried out for central nervous system TB by 79.6, 51.9, and 46.3% of the respondents, respectively. For patients with human immunodeficiency virus-TB coinfection, the preferred antiretroviral therapy included dolutegravir 50 mg twice a day (56.8%). Comparing with the recommendations of the main guidelines, the practices are not totally consistent. Conclusion: this study shows heterogeneous practices, particularly for diagnosis, and isolation, although rapid molecular testing is implemented in most centers. More standardization might be needed

Safety and efficacy of exposure to bedaquiline-delamanid in multidrug-resistant tuberculosis : A case series from France and Latvia

publishersversionPeer reviewe

Pregnancy in patients with tuberculosis: A TBNET cross-sectional survey

BACKGROUND: Objectives: To determine whether the incidence of tuberculosis with pregnancy is more common than would be expected from the crude birth rate; to see whether there is significant delay in the diagnosis of tuberculosis during pregnancy. METHOD: Design: A cross-sectional survey. SETTING: 13 tuberculosis clinics within different European countries and the USA. POPULATION/SAMPLE: All patients with tuberculosis seen at these clinics for a period\u2009>\u20091 year. INSTRUMENT: Questionnaire survey based on continuous data collection. MAIN OUTCOME MEASURES: number and proportion of women with tuberculosis who were pregnant; timing of diagnosis in relation to pregnancy, including those who were pregnant or delivered in the 3 months prior to the diagnosis of TB and those who developed TB within 3 months after delivery. RESULTS: Pregnancy occurred in 224 (1.5 %) of 15,217 TB patients and followed the expected rate predicted from the crude birth rate for the clinic populations. TB was diagnosed more commonly in the 3 months after delivery (n\u2009=\u2009103) than during pregnancy (n\u2009=\u200968; \u3c7 2\u2009=\u200925.1, P\u2009<\u20090.001). CONCLUSIONS: TB is diagnosed more frequently after delivery, despite variations in local TB incidence and healthcare systems

Impact of the COVID-19 pandemic on the real-world diagnostic infrastructure for tuberculosis-An ESGMYC collaborative study

We determined the impact of the COVID-19 pandemic on mycobacterial diagnostic services. 40 laboratories from 22 countries completed an online questionnaire covering the redeployment of the laboratory infrastructure and/or staff for SARS-CoV-2 testing, staff shortages and supply chain disruptions. 28 laboratories reported monthly numbers of samples processed for mycobacterial investigations and monthly numbers of M. tuberculosis complex (MTBC) PCRs performed between October 1st 2018 and October 31st 2020. More than half (23/40) of the participating TB laboratories reported having performed COVID-19 diagnostics in the early phase of the pandemic, in part with negative impact on the mycobacterial service activities. All participating laboratories reported shortages of consumables and laboratory equipment due to supply chain issues. Average monthly sample numbers decreased by 24% between January 2020 and October 2020 compared to pre-pandemic averages. At the end of the study period, most participating laboratories had not returned to pre-pandemic average MTBC PCR throughput

AA-amyloidosis in cats (Felis catus) housed in shelters.

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis

Treatment outcome definitions in nontuberculous mycobacterial pulmonary disease: an NTM-NET consensus statement

Nontuberculous mycobacterial pulmonary diseases (NTM-PD) are increasingly recognised as opportunistic infections of humans. These chronic pulmonary infections have two main presentations. The first is a fibro-cavitary disease, that occurs in patients with pre-existing pulmonary diseases, such as chronic obstructive pulmonary disease, bronchiectasis, previous tuberculosis or other structural lung disease. The second presentation is a nodular- bronchiectatic disease of primarily the lingula and middle lobe that tends to affect a middle- aged and elderly female population [1]. Treatment of NTM-PD requires long-term administration of complex multidrug therapies that are species-specific. Currently recommended regimens are supported by a very limited evidence base [2, 3]. The increasing incidence of NTM-PD has sparked increased interest in performing prospective randomised clinical trials [4]. One of the drawbacks of the existing case series and clinical trials is that they have applied different outcome measures [5]. This hampers meta-analyses, which are important in these still understudied infectious diseases. To enhance the quality and interpretability of the results of future trials and retrospective cohort studies, we aimed to formulate clear and broadly acceptable outcome definitions for NTM-PD treatment

Tuberculose à bacilles résistants aux antibiotiques en France : épidémiologie et prise en charge

Tuberculosis is the ninth leading cause of death worldwide. Progress in controlling this disease has been slowed down by multiple factors, including the emergence of multidrug-resistant (MDR) strains. MDR tuberculosis treatment is long, toxic, and often not effective. After more than 40 years of draught, two new drugs have been approved for the treatment of MDR tuberculosis: bedaquiline and delamanid. Globally, there have been considerable delays in the introduction of these new drugs in clinical practice, as shown by the little number of studies which are available in literature. The studies described in this manuscript have described cohorts of patients affected by MDR tuberculosis and treated with bedaquiline and/or delamanid in France: the main finding was a satisfying safety, even for prolonged treatment durations and for the association of the two new drugs. In addition, the microbiological efficacy of bedaquiline was shown to be comparable to the one of the fluoroquinolones, the most effective antibiotic class to treat MDR tuberculosis. In another study, we have shown the rapid appearance of bedaquiline resistance in France, an unexpected finding in particular for the cases of primary resistance. Notwithstanding the methodologic weaknesses associated with observational and retrospective studies, this work has increased the evidence on safety and efficacy of MDR tuberculosis treatment with the new drugs. The next step will be represented by the establishment of a prospective national research cohort of MDR tuberculosis cases.La tuberculose est la neuvième cause de mortalité dans le monde. Les progrès pour contrôler cette maladies ont été ralentis par plusieurs facteurs, notamment la diffusion de souches de tuberculose à bacilles multirésistants aux antibiotiques (MDR). Le traitement de la tuberculose MDR est long, toxique, et souvent inefficace. Après plus de 40 ans de pénurie, deux nouveaux médicaments ont été approuvé pour le traitement de la tuberculose MDR : la bédaquiline et le delamanide. Globalement, il y eu des délais considérables dans l'introduction de ces nouveaux médicaments dans la pratique clinique, comme souligné par le faible nombre d'études présentes en littérature. Les études présentés dans ce travail ont décrit des cohortes de patients atteints de tuberculose MDR et traités par bédaquiline et/ou delamanide en France, en montrant d'abord une tolérance satisfaisante, même pour des durées prolongées de traitement et pour l'association des deux nouveaux médicaments. En outre, l'efficacité microbiologique de la bédaquiline apparait comparable à celle des fluoroquinolones, la classe d'antibiotiques la plus efficace pour la tuberculose MDR. Dans une autre étude, l'on a mis en évidence l'apparition rapide de la résistance à la bédaquiline en France, ce qui était inattendu, en particulier pour les cas de résistance primaire. Malgré les limitations méthodologiques associées aux études observationnelles et rétrospectives, ce travail a permis d'augmenter les connaissances sur la tolérance et l'efficacité du traitement avec les nouvelles molécules pour la tuberculose MDR. Une suite des recherches est envisagée avec la mise en place d'une cohorte national prospective des cas MDR

Bedaquiline for the treatment of multidrug-resistant tuberculosis: another missed opportunity?

International audienceScale-up of introduction of bedaquiline, as part of optimised treatment regimens, is supported by growing evidenc

Drug-resistant tuberculosis in France : epidemiology and management

La tuberculose est la neuvième cause de mortalité dans le monde. Les progrès pour contrôler cette maladies ont été ralentis par plusieurs facteurs, notamment la diffusion de souches de tuberculose à bacilles multirésistants aux antibiotiques (MDR). Le traitement de la tuberculose MDR est long, toxique, et souvent inefficace. Après plus de 40 ans de pénurie, deux nouveaux médicaments ont été approuvé pour le traitement de la tuberculose MDR : la bédaquiline et le delamanide. Globalement, il y eu des délais considérables dans l'introduction de ces nouveaux médicaments dans la pratique clinique, comme souligné par le faible nombre d'études présentes en littérature. Les études présentés dans ce travail ont décrit des cohortes de patients atteints de tuberculose MDR et traités par bédaquiline et/ou delamanide en France, en montrant d'abord une tolérance satisfaisante, même pour des durées prolongées de traitement et pour l'association des deux nouveaux médicaments. En outre, l'efficacité microbiologique de la bédaquiline apparait comparable à celle des fluoroquinolones, la classe d'antibiotiques la plus efficace pour la tuberculose MDR. Dans une autre étude, l'on a mis en évidence l'apparition rapide de la résistance à la bédaquiline en France, ce qui était inattendu, en particulier pour les cas de résistance primaire. Malgré les limitations méthodologiques associées aux études observationnelles et rétrospectives, ce travail a permis d'augmenter les connaissances sur la tolérance et l'efficacité du traitement avec les nouvelles molécules pour la tuberculose MDR. Une suite des recherches est envisagée avec la mise en place d'une cohorte national prospective des cas MDR.Tuberculosis is the ninth leading cause of death worldwide. Progress in controlling this disease has been slowed down by multiple factors, including the emergence of multidrug-resistant (MDR) strains. MDR tuberculosis treatment is long, toxic, and often not effective. After more than 40 years of draught, two new drugs have been approved for the treatment of MDR tuberculosis: bedaquiline and delamanid. Globally, there have been considerable delays in the introduction of these new drugs in clinical practice, as shown by the little number of studies which are available in literature. The studies described in this manuscript have described cohorts of patients affected by MDR tuberculosis and treated with bedaquiline and/or delamanid in France: the main finding was a satisfying safety, even for prolonged treatment durations and for the association of the two new drugs. In addition, the microbiological efficacy of bedaquiline was shown to be comparable to the one of the fluoroquinolones, the most effective antibiotic class to treat MDR tuberculosis. In another study, we have shown the rapid appearance of bedaquiline resistance in France, an unexpected finding in particular for the cases of primary resistance. Notwithstanding the methodologic weaknesses associated with observational and retrospective studies, this work has increased the evidence on safety and efficacy of MDR tuberculosis treatment with the new drugs. The next step will be represented by the establishment of a prospective national research cohort of MDR tuberculosis cases