The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

BACKGROUND: Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. METHODS: We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. FINDINGS: From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. INTERPRETATION: No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. TRIAL REGISTRATION: Registration: PROSPERO (CRD42022309818).

The Role of Blood Gas Analysis in the Post-Acute Phase of COVID-19 Pneumonia

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Evidence-based Definition for Extensively Drug-Resistant Tuberculosis.

Rationale: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as TB with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]), any fluoroquinolone (FQ), and any second-line injectable drug (SLID). In 2019, the World Health Organization issued new recommendations for treating patients with drug-resistant TB, substantially limiting the role of SLIDs in MDR-TB treatment and thus putting the definition of XDR-TB into question. Objectives: To propose an up-to-date definition for XDR-TB. Methods: We used a large data set to assess treatment outcomes for patients with MDR-TB exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We performed logistic regression to estimate the adjusted odds ratios (aORs) for an unfavorable treatment outcome (failure, relapse, death, loss to follow-up), and estimates were stratified by the resistance pattern (FQ and/or SLID) and group A drug use (moxifloxacin/levofloxacin, linezolid, and/or bedaquiline). Measurements and Main Results: We included 11,666 patients with MDR-TB; 4,653 (39.9%) had an unfavorable treatment outcome. Resistance to FQs increased the odds of an unfavorable treatment outcome (aOR, 1.91; 95% confidence interval [CI], 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQs and/or SLIDs. Among patients with XDR-TB, compared with persons receiving no group A drug, aORs for an unfavorable outcome were 0.37 (95% CI, 0.20-0.69) with linezolid only, 0.40 (95% CI, 0.21-0.77) with bedaquiline only, and 0.21 (95% CI, 0.12-0.38) with both. Conclusions: Our study supports a new definition of XDR-TB as MDR-TB and additional resistance to FQ plus bedaquiline and/or linezolid and helps assess the adequacy of this definition for surveillance and treatment choice.

Tuberculosis elimination: where are we now?

Tuberculosis (TB) still represents a major public health issue in spite of the significant impact of the efforts made by the World Health Organization (WHO) and partners to improve its control. In 2014 WHO launched a new global strategy (End TB) with a vision of a world free of TB, and a 2035 goal of TB elimination (defined as less than one incident case per million). The aim of this article is to summarise the theoretical bases of the End TB Strategy and to analyse progresses and persistent obstacles on the way to TB elimination.The evolution of the WHO recommended strategies of TB control (Directly Observed Therapy, Short Course (DOTS), Stop TB and End TB) are described and the concept of TB elimination is discussed. Furthermore, the eight core activities recently proposed by WHO as the milestones to achieve TB elimination are discussed in detail. Finally, the recently published experiences of Cyprus and Oman on their way towards TB elimination are described, together with the regional experience of Latin America.New prevention, diagnostic and treatment tools are also necessary to increase the speed of the present TB incidence decline.

Hoja de ruta para la eliminación de la tuberculosis en Latinoamérica y el Caribe / Roadmap for Tuberculosis Elimination in Latin America and the Caribbean

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La diabetes se asocia con reacciones adversas graves en la tuberculosis multirresistente / Diabetes is Associated with Severe Adverse Events in Multidrug-Resistant Tuberculosis

Introducción: La diabetes mellitus (DM), una enfermedad muy frecuente en México, es un factor de riesgo bien conocido para el desarrollo de tuberculosis (TB). Sin embargo, se desconoce en qué medida la DM predispone al desarrollo de reacciones adversas (RA) a los fármacos anti-tuberculosis y/o si predispone a un peor resultado en pacientes con pacientes con TB multirresistente (TB-MR) y TB extremadamente resistente (TB-XR). El objetivo principal de este estudio fue describir los resultados del tratamiento anti-tuberculosis, el impacto de la DM y la prevalencia de RA en una cohorte de pacientes con TB pulmonar MR/XR tratados en el centro de referencia nacional para TB, en la Ciudad de México. Resultados: Entre 2010 y 2015 se incluyeron 90 pacientes -73 con TB-MR (81,1%), 11 con TB pre-XR (12,2%) y 6 (6,7%) con TB-XR-, 49 (54,4%) de los cuales tenían DM y 3 con co-infección por el virus de la inmunodeficiencia humana (VIH) (3,3%). El diagnóstico se realizó mediante cultivo y pruebas de fármaco-sensibilidad (PFS) en el 98% de los pacientes y mediante prueba molecular en un caso. La presencia de DM se asoció con un mayor riesgo de RA graves, tales como nefrotoxicidad (odds ratio [OR] = 6,5; intervalo de confianza del 95% [IC 95%]: 1,9-21,8) e hipotiroidismo (OR = 8,8; IC 95%: 1,8-54,2), aunque no con peor resultado del tratamiento. onclusiones: Nuestros datos sugieren que la DM no tiene un impacto sobre los resultados del tratamiento anti-tuberculosis de segunda línea, pero los pacientes con DM tienen mayor riesgo de presentar RA graves secundarias al tratamiento, tales como nefrotoxicidad e hipotiroidismo

Introduction: Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City. Results: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR] = 6.5; 95% Confidence Interval [95% CI]: 1.9-21.8) and hypothyroidism (OR = 8.8; 95% CI: 1.8-54.2), but not for a worse outcome. Conclusions: Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism

Breaking the barriers: Migrants and tuberculosis.

Tuberculosis (TB) can represent an important clinical and public health in developing and developed countries. Low- and middle-income countries are facing an epidemic which is difficult to address because of the drug-resistance spread and the association of TB with HIV/AIDS. High-income countries, whose TB incidence has decreased in the last decades, can be involved in new TB epidemic waves owing to social, healthcare, and economic hurdles and challenges. In particular, migrants coming from high TB incidence countries can represent a new epidemiological issue in the TB care and control in geographical areas where primary care and specialized centres are not equipped to face the clinical and public health issues associated with the TB disease. The healthcare management of individuals with a latent TB infection or the TB disease is heterogeneous and different policies are in place in Europe, and, specifically, in EU countries. Scientific evidence on how to early and efficiently detect TB cases is missing, as well as diagnostic tools to diagnose those who have latent TB infection do not show adequate accuracy. Countries like Greece and Italy have political difficulties in the management of migrants and the poor living conditions in the migration centres can increase the probability of Mycobacterium tuberculosis transmission. A clear advocacy and political commitment are urgently required. The current migration trends represent a threat from a human and a healthcare perspective. New homogeneous and target-oriented policies and strategies are needed to improve the health of the migrant and of the autochthonous populations.

Estrategias de la OMS para el tratamiento de la tuberculosis resistente / WHO strategies for the management of drug-resistant tuberculosis

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Recommendations Concerning the Therapeutic Approach to Immunocompromised Children With Tuberculosis.

PURPOSE: This article describes the recommendations of a group of scientific societies concerning the therapeutic approach to immunocompromised children with tuberculosis (TB). METHODS: Using the Consensus Conference method, relevant publications in English were identified by a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception until December 31, 2014. FINDINGS: On the basis of their clinical experience and the published evidence, the group of experts concluded that, although immunosuppressed subjects are at greater risk of developing TB, none of the signs or symptoms is sensitive or specific enough to enable a diagnosis. Immunocompromised patients are at greater risk of developing extrapulmonary forms of TB, especially if they are adolescents, whereas pulmonary forms are more prevalent among younger patients. When TB is suspected, a combination of skin and immunologic tests and other clinical, radiologic, and microbiologic examinations can be used to assess the risk of infection or disease. If the TB diagnosis is confirmed, immunocompromised children should be treated by using a standard regimen with a minimum of 4 drugs for at least 9 to 12 months, during which the tolerability of the drugs and their interactions should be carefully evaluated. IMPLICATIONS: It is difficult to diagnose and treat TB in immunocompromised children. Thus, all pediatric patients undergoing immunosuppressive therapy who develop TB should be diagnosed and treated at a TB reference center, which should also be responsible for the recommended follow-up.