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Tuberculosis (TB) diagnosis and management in special populations remain challenging. Data about TB and transgender individuals is scarce, and strategies aimed at reducing the TB burden in this at-risk group are needed. We conducted an observational monocentric study from a national reference center for TB, including transgender individuals with active TB in a low-TB burden country (Italy), over 34 years (1990-2023). Sixty-six transgender males and two transgender females (median age 30 years, interquartile range 26-38 years, 65 migrants) were included. Most patients (38/66, 57.6%) lived in poor social conditions. 65.2% (43/66) of patients were people living with HIV. Multidrug- and rifampicin-resistant tuberculosis and isoniazid-resistant TB were diagnosed in five (7.6%) and three (4.5%) patients, respectively. The overall treatment success rate was 72.7% (48/66 patients), with differences observed according to social conditions. Our study highlights the need for a tailored approach to increase treatment success in this at-risk population.
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Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript.
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BACKGROUND: Human migration and the ever-changing geopolitical scenarios are redefining the epidemiology and the management of tuberculosis (TB), especially in low-TB burden countries welcoming high rates of people from high-TB burden countries. METHODS: We conducted an observational retrospective mono-centric study in a Northern-Italy TB reference centre from 1 January 1990 to 31 December 2019, focusing on the differences in epidemiology, resistance patterns and treatment outcomes between Italians and migrants with active TB. Data were collected from medical records. RESULTS: A total of 10555 patients were included, 4614 Italians and 5941 migrants. Among migrants, higher rates of rifampin-resistant (RR) or multidrug-resistant (MDR) TB were reported, as well as higher rates of loss to follow-up. Among Italians, higher mortality rates and a higher number of extrapulmonary TB cases were found. CONCLUSION: Our study describes one of the largest cohorts of patients with active TB in Italy, highlighting the need for tailored approaches in native and migrant populations.
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Mycobacterium tuberculosis , Migrantes , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Estudos Retrospectivos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Itália/epidemiologiaRESUMO
Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB.
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Even if major improvements in therapeutic regimens and treatment outcomes have been progressively achieved, tuberculosis (TB) remains the leading cause of death from a single infectious microorganism. To improve TB treatment success as well as patients' quality of life, drug-drug-interactions (DDIs) need to be wisely managed. Comprehensive knowledge of anti-TB drugs, pharmacokinetics and pharmacodynamic (PK/PD) parameters, potential patients' changes in absorption and distribution, possible side effects and interactions, is mandatory to built effective anti-TB regimens. Optimization of treatments and adherence to international guidelines can help bend the curve of TB-related mortality and, ultimately, decrease the likelihood of treatment failure and drop-out during anti-TB treatment. Aim of this paper is to describe the most relevant DDIs between anti-TB and other drugs used in daily clinical practice, providing an updated and "easy-to-use" guide to minimize adverse effects, drop-outs and, in the long run, increase treatment success.
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Assistência Ambulatorial/organização & administração , Antituberculosos/uso terapêutico , COVID-19/prevenção & controle , Telemedicina , Tuberculose/tratamento farmacológico , Assistência Ambulatorial/ética , COVID-19/epidemiologia , Ética Médica , Humanos , Itália/epidemiologia , Ambulatório Hospitalar , Pandemias , SARS-CoV-2RESUMO
Background: Tuberculosis (TB) unevenly affects individuals across the globe, especially in rural areas of low-income countries. Aim of the study was to assess the impact of social protection to increase TB awareness on treatment outcomes among TB patients in a rural area of Senegal. Materials & methods: The study, conducted in Fimela district (Senegal) from 1 January 2010 to 31 December 2019 and the intervention started from 31 January 2013, includes activities to increase awareness, active case finding, active follow-up and social protection. Results: Overall, 435 subjects - mainly male and young - were included in the analysis. Among TB cases, 94% had pulmonary involvement, 87% had no previous TB history, and 6% resulted positive HIV. Improved outcome was observed once intervention began (from 71 to 91%, p < 0.001); whereas mortality decreased (from 15 to 5%; p < 0.001), especially for those HIV co-infected for whom TB mortality rate dropped from 70 to 29%. Conclusion: After beginning the cooperation program, TB treatment success increased as a result of the decline of mortality, especially in people living with HIV.
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População Rural , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/uso terapêutico , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Política Pública , Senegal/epidemiologia , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto JovemAssuntos
Coinfecção/diagnóstico , Acessibilidade aos Serviços de Saúde , Infecção Latente/diagnóstico , Programas de Rastreamento , Tuberculose/diagnóstico , Coinfecção/economia , Coinfecção/epidemiologia , Coinfecção/terapia , Custos de Cuidados de Saúde , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/ética , Humanos , Incidência , Infecção Latente/economia , Infecção Latente/epidemiologia , Infecção Latente/terapia , Programas de Rastreamento/economia , Programas de Rastreamento/ética , Valor Preditivo dos Testes , Prognóstico , Fatores Socioeconômicos , Tuberculose/economia , Tuberculose/epidemiologia , Tuberculose/terapiaRESUMO
COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients' ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000â¯cells/mm3) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500â¯cells/mm3) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology.
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COVID-19/terapia , Terapia de Imunossupressão/métodos , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Humanos , Imunidade/fisiologia , Testes de Liberação de Interferon-gama/estatística & dados numéricos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Itália/epidemiologia , Tuberculose Latente/epidemiologia , Tuberculose Latente/imunologia , Tuberculose Latente/prevenção & controle , Linfopenia/imunologia , Masculino , Estudos Retrospectivos , SARS-CoV-2/genética , Índice de Gravidade de DoençaRESUMO
The emerge of drug-resistant tuberculosis (TB) strain in recent decades is hampering the efforts of the international community to eliminate the disease worldwide. The World Health Organization (WHO) has drafted many strategies to achieve this ambitious goal. In the very beginning, the aim was to standardize inadequate regimens used in many countries and, thereafter, evolved to tackle the social determinants which hinder TB elimination. However, following the path of narrowing the clinical vision to deal with TB, there is an increased need to personalize the treatment considering both patients and pathogen unique characteristics. In our narrative review, we report the advantages and the backwards in developing a method to implement the concept of precision medicine to the treatment of TB. In this dissertation, we highlight the importance to address different aspects of the diseases encompassing the host and pathogen features, as well as the needs to further implement an adequate follow-up based on the available resources. Nevertheless, many things may hamper the vision of precision medicine in TB, such as the complexity and the costs to develop novel compounds and the costs related to global-scale implementation of patient-centered follow-up. To achieve the ambitious goal of TB elimination, a radical change in TB treatment is needed in order to give a more comprehensive approach based both on patients' peculiarities and driven by drug susceptibility tests and whole-genome sequencing.
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Tuberculosis (TB) and humans have coexisted for more than 40,000 years; however TB remains a global threat to human kind. The international community has developed new tools for early detection, but TB strains evolved acquiring resistance to first-line therapeutic drugs with increasing treatment challenges. Furthermore, TB has formed also an alliance with human immunodeficiency virus; in this way the poorest populations are most affected. The current vaccine planning activity includes 14 new vaccines against TB (11 of those in the phaseII/III) developed with different techniques. Now, more than ever, new anti-TB drugs and new anti-TB regimens are urgently required as well as universal health care and social protection in order to tackle down both hard to treat TB and the social determinants of TB. Coordinated actions and sharing of information are needed to aspire everywhere to the best clinical practices and improve quality of life of patients and their families.
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Antituberculosos/uso terapêutico , Desenvolvimento de Medicamentos/tendências , Mycobacterium tuberculosis/efeitos dos fármacos , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose/tratamento farmacológico , Difusão de Inovações , Previsões , Interações Hospedeiro-Patógeno , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/imunologia , Tuberculose/microbiologiaRESUMO
Tuberculosis is an ancient infectious disease caused by the bacillus Mycobacterium tuberculosis that is still nowadays afflicting humans all over the world. It causes ill-health for 10 million people each year. Tuberculosis (TB) has been the leading cause of death from a single infectious agent, ranking above HIV/AIDS. In recent years, infection with HIV represents a major risk factor predisposing for infection and TB is the most common cause of AIDS-related death. Despite the treatment of HIV-associated TB has essentially retraced that recommended in HIV-negative cases, it has disclosed some additional challenges over the years. The association of delayed and missed diagnoses, logistic accidents and some well-known complications of HIV and TB treatment co-administration has contributed to 300,000 people living with HIV died from a preventable and curable disease like TB in 2017. The evaluation of new diagnostic and therapeutic approaches with the struggle to erase stigma are essential to successfully manage HIV-TB coinfection.
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Coinfecção , Infecções por HIV/epidemiologia , Pandemias , Tuberculose/epidemiologia , África/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/virologia , Humanos , Preconceito , Prognóstico , Medição de Risco , Fatores de Risco , Estereotipagem , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Tuberculose/mortalidadeRESUMO
Clofazimine (CFZ), an old hydrophobic riminophenazine, has a wide range of antimycobacterial activity ranging from leprosy to nontuberculous mycobacterial diseases. CFZ has several advantages such as a favorable pharmacokinetic profile, dose-dependent side effects as well as low price. In this narrative review, we have assessed the clinical development of CFZ, starting from the potential in vitro mechanism of actions, to the spectrum of side effects and potential drug-drug interactions, highlighting its current place in therapy and future possible use in leprosy, nontuberculous mycobacterial diseases and drug-resistant tuberculosis.
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Antibacterianos/uso terapêutico , Clofazimina/uso terapêutico , Hanseníase/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Animais , Antibacterianos/efeitos adversos , Farmacorresistência Bacteriana , Humanos , Hanseníase/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacosRESUMO
BACKGROUND: The increased incidence of drug-resistant TB is a major challenge for effective TB control. Limited therapeutic options and poor treatment outcomes of DR-TB may increase drug-resistance rates. The objective of the study is to retrospectively compare MDR-TB and pre-XDR-TB treatment regimens and outcomes in two large TB reference centres in Italy from January 2000 to January 2015. METHODS: A retrospective, multicentre study was conducted at the Regional TB Reference Centre Villa Marelli Institute (Milan) and at the Reference Center for MDR-TB and HIV-TB, Eugenio Morelli Hospital (Sondalo). The supra-national Reference Laboratory in Milan performed DST. Inclusion criteria were: age ≥ 18 and culture-confirmed diagnosis of MDR- or pre-XDR TB. Chi-square or Fisher exact test was used to detect differences in the comparison between treatment outcomes, therapeutic regimens, and drug-resistances. Computations were performed with STATA 15. RESULTS: A total of 134 patients were selected. Median (IQR) age at admission was 33 (26-41) years and 90 patients (67.2%) were male. Pulmonary TB was diagnosed in 124 (92.5%) patients. MDR- and pre-XDR-TB cases were 91 (67.9%) and 43 (32.1%), respectively. The WHO shorter MDR-TB regimen could have been prescribed in 16/84 (19.1%) patients. Treatment success was not statistically different between MDR- and pre-XDR-TB (81.3% VS. 81.4%; P = 0.99). Mortality in MDR-TB and pre-XDR-TB groups was 4.4 and 9.3%, respectively (P = 0.2). Median duration of treatment was 18 months and a total of 110 different regimens were administered. Exposure to linezolid, meropenem, and amikacin was associated with a better outcome in both groups (P = 0.001, P < 0.001, and P = 0.004, respectively). CONCLUSIONS: Tailored treatment regimens based on DST results can achieve successful outcomes in patients with pre-XDR-TB.
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Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Amicacina/farmacologia , Amicacina/uso terapêutico , Antituberculosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Feminino , Humanos , Itália , Laboratórios Hospitalares , Linezolida/farmacologia , Linezolida/uso terapêutico , Masculino , Meropeném/farmacologia , Meropeném/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/mortalidadeRESUMO
BACKGROUND: Since 2013 StopTB Italia Onlus supports the Senegalese National Tuberculosis Programme by improving diagnostic capability with technological interventions, ameliorating educational programs for health care personnel, rising awareness among civil society and providing economical support for patients during treatment. The purpose of our study was to assess the preliminary results of an interventional cooperation project in a peripheral health care facility in Senegal. METHODS: An observational, retrospective, pre-post study was conducted to compare Tuberculosis (TB) retention in care and outcome between a one-year period before and a four-year period after. RESULTS: Overall, 239 patients with active TB were included, 196 (82%) of whom after the starting of the collaboration project. At diagnosis 35/43(81.4%) vs 151/196 (77%) patients were smear sputum positive before and after the beginning of the project, respectively.At 2 months follow up 23/35 (65.7%) patients in 2012 vs. 139/151 (92%) patients in 2013-2016 had negative control AFB stain (p = 0.249), 4/35 (11.4%) vs 12/151 (8%) patients remained AFB stain positive (p = 0.17), 7/35 (20%) vs 0/151 died before the 2 months follow up (p < 0.0001). TB treatment outcome was more frequently favourable after the beginning of cooperation 29/43 (67.4%) vs. 176/196 (89.8%) patients, (p < 0.0001). Patients' mortality during treatment decreased from 8/43 (18.6%) in 2012 to 11/196 (5.6%) patients in the following years (p = 0.009). CONCLUSION: The implementation of diagnostic procedures, if integrated in a socio-economical intervention, impacts favourably on TB retention in care and treatment outcomes.
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BACKGROUND: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). METHODS: IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients' demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. CONCLUSIONS: IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease's awareness. TRIAL REGISTRATION: Clinicaltrial.gov: NCT03339063.