Factors Associated with Non-Adherence to Tuberculosis Preventive Treatment among Adult Contacts of Pulmonary Tuberculosis Cases with Latent Tuberculosis Infection in Catalonia, Spain, in 2019-2021.

The aim of this study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection for new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables; a p < 0.05 was considered statistically significant. Multiple logistic regression analysis was used to detect the independent factors associated with TB preventive treatment non-adherence; a p < 0.05 was considered statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: "exposure at school or workplace" (aOR = 3.34), "exposure to an index case without laboratory confirmation of TB" (aOR = 2.07), "immigrant contact" (aOR = 1.81), "male gender" (aOR = 1.75) and "exposure duration < 6 h per week or sporadic" (aOR = 1.60. By contrast, the factor "short-term TB preventive treatment regimen" (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Cost-effectiveness of active tuberculosis screening among high-risk populations in low tuberculosis incidence countries: a systematic review, 2008 to 2023.

BackgroundIn countries with a low TB incidence (≤ 10 cases/100,000 population), active pulmonary tuberculosis (PTB) mostly affects vulnerable populations with limited access to healthcare. Thus, passive case-finding systems may not be successful in detecting and treating cases and preventing further transmission. Active and cost-effective search strategies can overcome this problem.AimWe aimed to review the evidence on the cost-effectiveness (C-E) of active PTB screening programmes among high-risk populations in low TB incidence countries.MethodsWe performed a systematic literature search covering 2008-2023 on PubMed, Embase, Center for Reviews and Dissemination, including Database of Abstracts of Reviews of Effects (DARE), National Health Services Economic Evaluation Database (NHS EED), Global Index Medicus and Cochrane Central Register of Controlled Trials (CENTRAL).ResultsWe retrieved 6,318 articles and included nine in this review. All included studies had an active case-finding approach and used chest X-ray, tuberculin skin test, interferon-gamma release assay and a symptoms questionnaire for screening. The results indicate that screening immigrants from countries with a TB incidence > 40 cases per 100,000 population and other vulnerable populations as individuals from isolated communities, people experiencing homelessness, those accessing drug treatment services and contacts, is cost-effective in low-incidence countries.ConclusionIn low-incidence countries, targeting high-risk groups is C-E. However, due to the data heterogenicity, we were unable to compare C-E. Harmonisation of the methods for C-E analysis is needed and would facilitate comparisons. To outline comprehensive screening and its subsequent C-E analysis, researchers should consider multiple factors influencing screening methods and outcomes.

A longitudinal prospective study of active tuberculosis in a Western Europe setting: insights and findings.

PURPOSE: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. METHODS: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. RESULTS: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. CONCLUSIONS: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.

Risk of tuberculosis among pulmonary tuberculosis contacts: the importance of time of exposure to index cases.

INTRODUCTION: The intensity of exposure to index cases of tuberculosis [TB] may increase the risk of TB in their contacts. The aim was to determine TB risk factors among contacts of TB index cases. METHODS: A cohort study was carried out in the contacts of pulmonary TB cases registered by the epidemiological surveillance network from 01/01/2019 to 06/30/2021. The factors associated with the risk of TB in contacts were determined using the adjusted odds ratio [aOR] and its 95% confidence interval [CI]. RESULTS: From 847 TB cases, 7087 contacts were identified. The prevalence of TB was 2.0% [145/7087] and was higher in < 5 years compared to those ≥ 65 years [4.4% versus 1.2%; p < 0.001], in those exposed ≥ 6 h daily [4%], and < 6 h daily [1.6%] with respect to weekly exposure of < 6 h [0.7%; p < 0.001]. Those contacts exposed ≥ 6 h daily [aOR= 6.9; 95%CI:2.1-22.1], < 5 years [aOR= 8.3; 95%CI:1.8-37.8] and immigrants [aOR= 1.7; 95%CI:1.1-2.7] had a higher risk of TB. CONCLUSIONS: The risk of TB increases with the time of exposure to the index case and this risk is also higher in < 5 years and immigrants. Contact tracing has a high yield for detecting new cases of TB.

Development and Evaluation of an NTM-IGRA to Guide Pediatric Lymphadenitis Diagnosis.

BACKGROUND: Diagnosis of nontuberculous mycobacteria (NTM) infections remains a challenge. In this study, we describe the evaluation of an immunological NTM-interferon (IFN)-γ release assay (IGRA) that we developed using glycopeptidolipids (GPLs) as NTM-specific antigens. METHODS: We tested the NTM-IGRA in 99 samples from pediatric patients. Seventy-five were patients with lymphadenitis: 25 were NTM confirmed, 45 were of unknown etiology but compatible with mycobacterial infection and 5 had lymphadenitis caused by an etiologic agent other than NTM. The remaining 24 samples were from control individuals without lymphadenitis (latently infected with M. tuberculosis , uninfected controls and active tuberculosis patients). Peripheral blood mononuclear cells were stimulated overnight with GPLs. Detection of IFN-γ producing cells was evaluated by enzyme-linked immunospot assay. RESULTS: NTM culture-confirmed lymphadenitis patient samples had a significantly higher response to GPLs than the patients with lymphadenitis of unknown etiology but compatible with mycobacterial infection ( P < 0.001) and lymphadenitis not caused by NTM ( P < 0.01). We analyzed the response against GPLs in samples from unknown etiology lymphadenitis but compatible with mycobacterial infection cases according to the tuberculin skin test (TST) response, and although not statistically significant, those with a TST ≥5 mm had a higher response to GPLs when compared with the TST <5 mm group. CONCLUSIONS: Stimulation with GPLs yielded promising results in detecting NTM infection in pediatric patients with lymphadenitis. Our results indicate that the test could be useful to guide the diagnosis of pediatric lymphadenitis. This new NTM-IGRA could improve the clinical handling of NTM-infected patients and avoid unnecessary misdiagnosis and treatments.

Factors Associated with Treatment Prescription to Pulmonary Tuberculosis Contacts in Catalonia (2019-2021): A Population-Based Epidemiological Study.

In countries with low tuberculosis (TB) incidence, the systematic testing and treatment of latent TB infection (LTBI) in contacts of pulmonary TB index cases is the standard of care. The objective of this study, conducted in Catalonia over 2019-2021, was to assess the factors associated with LTBI treatment prescription to close contacts of pulmonary TB index cases. In this population-based epidemiological study of LTBI prevalence among pulmonary TB contacts between 2019 and 2021, multiple logistic backward stepwise regression was used to identify the factors associated with treatment prescription, for which the adjusted odds ratio (aOR) and 95% confidence intervals (CI) were calculated. A total of 1487 LTBI contacts of 542 pulmonary TB index cases were studied, 80.6% of whom received a prescription. The factors associated with LTBI treatment prescription were exposure ≥6 h/day (aOR 14.20; 95% CI 5.22-38.66) and exposure <6 h/day (aOR 7.32, 95% CI 2.48-21.64), whereas the factors associated with no LTBI treatment prescription were age ≥55 years (aOR 0.22, 95% CI 0.08-0.64) and bacillus Calmette-Guerin vaccination (aOR 0.38, 95% CI 0.16-0.90). Crucial to LTBI treatment prescription is information on the contact's duration of exposure to pulmonary TB, not only for contacts exposed for ≥6 h/day, but also for contacts with lower daily exposure levels.

Latent Tuberculosis Infection in Users of Drug Dependence Care and Follow-up Centers in Barcelona in 2017-2021: A Cross-sectional Descriptive Study.

Introduction: People who consume drugs have a higher risk of latent tuberculosis infection (LTBI). Our objective was to study the characteristics of people who use drugs and who attended the Centers for Drug Dependence Care and Follow-up of Barcelona during 2017-2021 and presented LTBI or did not perform the reading of the tuberculin skin test (TST) after the test had been done. Methods: A cross-sectional, descriptive study in Centers for Drug Dependence Care and Follow-up of Barcelona was performed during 2017-2021. The sociodemographic and epidemiological profile of people who use drugs that underwent a TST was analyzed and were examined the factors associated with LTBI. Additionally, the same sociodemographic and epidemiological analyses were made in PWUD that did not perform the reading of the TST after the test had been done. Adjusted odds ratios (ORa) and 95% confidence intervals (95% CI) were calculated. Results: Nine hundred forty-eight persons were profiled. The prevalence of LTBI was 22.9%, and the following factors were associated with it: be older than 41 years; be users of CAS Baluard, or CAS Horta-Guinardó; coming from a WHO region of high TB incidence; be homeless; and low territorial socioeconomic index. The following factors were associated with not performing the reading of the TST after the test had been done: be users from the CAS Baluard, Barceloneta, Nou Barris and Robadors; be homeless and low TSI. Conclusions: This study improves TB control and highlights the need for this LTBI control program in CASs.

Introducción: Las personas que consumen drogas tienen un mayor riesgo de infección tuberculosa latente (ITL). Nuestro objetivo fue medir las características de las personas que cosumen drogas y que acudieron a los centros de atención y seguimiento (CAS) a las drogodependencias de Barcelona entre 2017-2021 y que presentaron ITL, así como conocer el perfil de las que no acudieron a la lectura de la prueba de la tuberculina (PT). Métodos: Se realizó un estudio descriptivo transversal en los centros de atención y seguimiento a las drogodependencias de Barcelona durante el periodo 2017-2021. Se analizó el perfil sociodemográfico y epidemiológico de las personas que consumen drogas que se sometieron a una PT y se examinaron los factores asociados a la ITL. Además, los mismos análisis sociodemográficos y epidemiológicos se realizaron en las personas que consumen drogas que no realizaron la lectura de la PT después de realizarla. Se calcularon las odds ratio ajustadas (ORa) y los intervalos de confianza de 95% (IC 95%). Resultados: Se estudiaron 948 personas. La prevalencia de ITL fue de 22,9%, y los factores asociados fueron: ser mayor de 41 años, ser usuarios del CAS Baluard, o del CAS Horta-Guinardó, provenir de una región de la Organización Mundial de la Salud de alta incidencia de TB, ser una persona sin hogar y bajo índice socioeconómico territorial (IST). Los siguientes factores se asociaron con no acudir a la lectura de PT después de la realización de la prueba: ser personas usuarias del CAS Baluard, Barceloneta, Nou Barris y Robadors; personas sin hogar y bajo IST. Conclusiones: Este estudio mejora el control de la TB y destaca la necesidad de este programa de control de ITL en los CAS.

Using a medication event monitoring system to evaluate self-report and pill count for determining treatment completion with self-administered, once-weekly isoniazid and rifapentine.

BACKGROUND: Treatment completion is essential for the effectiveness of any latent tuberculosis infection (LTBI) regimen. The Tuberculosis Trials Consortium (TBTC) Study 33 (iAdhere) combined self-report and pill counts - standard of care (SOC) with a medication event monitoring system (MEMS) to determine treatment completion for 12-dose once-weekly isoniazid and rifapentine (3HP). Understanding the performance of SOC relative to MEMS can inform providers and suggest when interventions may be applied to optimize LTBI treatment completion. METHOD: iAdhere randomized participants to directly observed therapy (DOT), SAT, or SAT with text reminders in Hong Kong, South Africa, Spain and the United States (U.S.). This post-hoc secondary analysis evaluated treatment completion in both SAT arms, and compared completion based on SOC with MEMS to completion based on SOC only. Treatment completion proportions were compared. Characteristics associated with discordance between SOC and SOC with MEMS were identified. RESULTS: Overall 80.8% of 665 participants completed treatment per SOC, compared to 74.7% per SOC with MEMS, a difference of 6.1% (95%CI: 4.2%, 7.8%). Among U.S. participants only, this difference was 3.3% (95% CI: 1.8%, 4.9%). Differences in completion was 3.1% (95% CI: -1.1%, 7.3%) in Spain, and 36.8% (95% CI: 24.3%, 49.4%) in South Africa. There was no difference in Hong Kong. CONCLUSION: When used for monitoring 3HP, SOC significantly overestimated treatment completion in U.S. and South Africa. However, SOC still provides a reasonable estimate of treatment completion of the 3HP regimen, in U.S., Spain, and Hong Kong.

Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection.

BACKGROUND: Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP. METHODS: We analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Among 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19-3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19-3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15-4.42). CONCLUSIONS: Although most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve. Clinical Trials Registration. NCT01582711.

Glycemic control and the risk of tuberculosis in patients with diabetes: A cohort study in a Mediterranean city.

Background: Diabetes mellitus (DM) is one of the leading chronic diseases globally and one of the most common causes of death, morbidity, and poor quality of life. According to the WHO, DM is also one of the main risk factors for developing active tuberculosis (TB). Subjects with DM are at a higher risk of infections, in addition to frequent micro and macrovascular complications, and therefore sought to determine whether poor glycemic control is linked to a higher risk of developing TB. Methods: We used a retrospective cohort of diabetic subjects to predict the incidence of TB. All DM patients were recruited from Ciutat Vella (the inner-city of Barcelona) from January 2007 until December 2016, with a follow-up period until December 2018 (≥2 years). Data were extracted from Barcelona's Primary Care medical record database - SIDIAP, and linked to the Barcelona TB Control Program. The incidence of TB and the impact of glycemic control were estimated using time-to-event curves analyzed by Cox proportional hazard regression. Hazard ratios (HRs) and 95% confidence intervals (CIs), unadjusted and adjusted by potential confounding variables, were also assessed, which included age, sex, diabetes duration, macrovascular and microvascular signs, BMI, smoking habit, alcohol consumption and geographical origin. Results: Of 8,004 DM patients considered for the study (equating to 68,605 person-years of follow-up), 84 developed TB [incidence rate = 70 (95% CI: 52-93) per 100,000 person-years]. DM subjects with TB were younger (mean: 52.2 vs. 57.7 years old), had higher values of glycosylated hemoglobin (HbA1c) (7.66 vs. 7.41%) and total triglycerides (122 vs. 105 mg/dl), and had twice the frequency of diabetic nephropathy (2.08 vs. 1.18%). The calculated incidence rate increased with increasing HbA1c: 120.5 (95% CI 77.2-179.3) for HbA1c ≥ 7.5%, 143 (95% CI 88.3-218.1) for HbA1c ≥ 8% and 183.8 (95% CI 105-298) for HbA1c ≥ 9%. An increase in the risk of TB was also observed according to a poorer optimization of glycemic control: adjusted HR 1.80 (95% CI 0.60-5.42), 2.06 (95% CI 0.67-6.32), and 2.82 (95% CI 0.88-9.06), respectively. Conclusion: Diabetic subjects with worse glycemic control show a trend toward a higher risk of developing TB.

Subjects With Diabetes Mellitus Are at Increased Risk for Developing Tuberculosis: A Cohort Study in an Inner-City District of Barcelona (Spain).

Background: Tuberculosis is the leading cause of mortality from lung infectious disease worldwide in recent years, and its incidence has re-emerged in large cities in low-incidence countries due to migration and socioeconomic deprivation causes. Diabetes mellitus and tuberculosis are syndemic diseases, with diabetes being considered a risk factor for developing tuberculosis. Objective: To investigate whether diabetic patients were at increased risk of tuberculosis living in an inner-district of a large city of northeastern Spain. Methods: Observational matched retrospective cohort study based on clinical records from the population of the lowest socioeconomic status in Barcelona (Ciutat Vella district). A cohort including patients with type 1 and type 2 diabetes mellitus in 2007 and new cases until 2016 (8004 subjects), matched 1:1 by sex and age with a non-diabetic cohort. Follow-up period was until December 31st 2018. We evaluated the risk of developing tuberculosis in diabetic patients compared to non-diabetic patients during the follow up period. We used time-to-event analysis to estimate the incidence of tuberculosis, and competing risks regression by clusters and conditional Cox regression models to calculate the hazard ratio (HR) and its 95% confidence intervals (CI). Results: Among the 16,008 included subjects, the median follow-up was 8.7 years. The mean age was 57.7 years; 61.2% men and 38.8% women in both groups. The incidence of tuberculosis was 69.9 per 100,000 person-years in diabetic patients, and 40.9 per 100,000 person-years in non-diabetic patients (HR = 1.90; CI: 1.18-3.07). After adjustment for the country of origin, chronic kidney disease, number of medical appointments, BMI, alcoholism and smoking, the risk remained higher in diabetic patients (1.66: CI 0.99-2.77). Additionally, subjects from Hindustan or with a history of alcohol abuse also showed a higher risk of developing tuberculosis (HR = 3.51; CI:1.87-6.57, and HR = 2.73; CI:1.22-6.12 respectively). Conclusion: People with diabetes mellitus were at higher risk of developing tuberculosis in a large cohort recruited in an inner-city district with a high incidence for this outcome, and low socioeconomic conditions and high proportion of migrants. This risk was higher among Hindustan born and alcohol abusers.

Inequities in the incidence and mortality due to COVID-19 in nursing homes in Barcelona by characteristics of the nursing homes.

BACKGROUND: Residents of Nursing Homes (NHs) have suffered greater impacts from the COVID-19 pandemic. However, the rates of COVID-19 in these institutions are heterogeneously distributed. Describing and understanding the structural, functional, and socioeconomic differences between NHs is extremely important to avoid new outbreaks. OBJECTIVES: Analyze inequalities in the cumulative incidences (CIs) and in the mortality rates (MRs) due to COVID-19 in the NHs of Barcelona based on the characteristics of the NHs. METHODS: Exploratory ecological study of 232 NHs. The dependent variables were the cumulative incidence and mortality rate due to COVID-19 in NHs between March and June 2020. Structural variables of the NHs were evaluated such as neighborhood socioeconomic position (SEP), isolation and sectorization capacity, occupancy, overcrowding and ownership. RESULTS: The cumulative incidence and mortality rate were higher in the low SEP neighborhoods and lower in those of high SEP neighborhoods. Regarding the isolation and sectorization capacity, Type B NHs had a higher risk of becoming infected and dying, while Type C had a lower risk of dying than Type A. Greater overcrowding was associated with greater morbidity and mortality, and higher occupancy was associated with higher incidence. The risk of becoming infected and dying in public NHs was significantly higher than for-profit NH. CONCLUSIONS: The social components together with the functional and infrastructure characteristics of the NHs influence the cumulative incidence and the mortality rate by COVID-19. It is necessary to redefine the care model in the NHs to guarantee the health of the residents.

Tobacco Smoking and Second-Hand Smoke Exposure Impact on Tuberculosis in Children.

Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays' (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9-12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79-11.94)] and active TB [aOR (95% CI): 3.40 (1.45-7.98)]. Moreover, IGRAs' sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response.

Impact of the COVID-19 pandemic on contact tracing of patients with pulmonary tuberculosis.

BACKGROUND: The COVID-19 pandemic could have negative effects on tuberculosis (TB) control. The objective was to assess the impact of the pandemic in contact tracing, TB and latent tuberculosis infection (LTBI) in contacts of patients with pulmonary TB in Catalonia (Spain). METHODS: Contact tracing was carried out in cases of pulmonary TB detected during 14 months in the pre-pandemic period (1 January 2019 to 28 February 2020) and 14 months in the pandemic period (1 March 2020 to 30 April 2021). Contacts received the tuberculin skin test and/or interferon gamma release assay and it was determined whether they had TB or LTBI. Variables associated with TB or LTBI in contacts (study period and sociodemographic variables) were analyzed using adjusted odds ratio (aOR) and the 95% confidence intervals (95% CI). RESULTS: The pre-pandemic and pandemic periods showed, respectively: 503 and 255 pulmonary TB reported cases (reduction of 50.7%); and 4676 and 1687 contacts studied (reduction of 36.1%). In these periods, the proportion of TB cases among the contacts was 1.9% (84/4307) and 2.2% (30/1381) (P = 0.608); and the proportion of LTBI was 25.3% (1090/4307) and 29.2% (403/1381) (P < 0.001). The pandemic period was associated to higher LTBI proportion (aOR = 1.3; 95% CI 1.1-1.5), taking into account the effect on LTBI of the other variables studied as sex, age, household contact and migrant status. CONCLUSIONS: COVID-19 is affecting TB control due to less exhaustive TB and LTBI case detection. An increase in LTBI was observed during the pandemic period. Efforts should be made to improve detection of TB and LTBI among contacts of TB cases.

Trends in the Epidemiology of Leishmaniasis in the City of Barcelona (1996-2019).

Background: Leishmaniasis is a neglected zoonosis produced by 20 different flagellated parasites of the Leishmania genus, a protozoan transmitted to humans and other vertebrates by the bite of dipteran insects of the Phlebotominae subfamily. It is endemic in Mediterranean countries and the number of cases is expected to increase due to climate change and migration. Prioritizing public health interventions for prevention and control is essential. The objective was to characterize the epidemiology and temporal trends in the incidence of human leishmaniasis in the city of Barcelona, between the years 1996 and 2019. Methods: A population-based, analytical observational study among residents in the city of Barcelona was conducted of all the cases of leishmaniasis reported between 1996 and 2019 to the Public Health Agency. The epidemiological survey contains clinical, diagnostic, and epidemiological data, including contact with suspicious mammals or insects. Annual incidence-rates were calculated by sex, age, and country of origin. Chi-square tests were used to assess association between studied risk factors, periods of time and type of leishmaniasis. Results: During the study period a total of 177 cases of leishmaniasis were reported in Barcelona, being 74.6% (n = 132) of the total cases in Spanish born, although within the foreign-born population the incidence was higher. Median age was 34 years (IQR = 10-48) and 121 (66.8%) were male. The main type was cutaneous (46%) followed by visceral (35.1%). The cumulative incidence was 0.47 per 100,000 inhabitants, with the highest incidence found in 2017 (1.60 per 100,000 inhabitants). A higher incidence was observed in the 0-4-year-old group (1.73 per 100,000 inhabitants), but increased during the study period for all age groups. There was an increase of foreign origin cases, and a decrease in the number of cases associated to any immunosuppression. Conclusion: In Barcelona, leishmaniasis incidence continues to be higher in people under 5 years of age, and 25-64 years old males, but it has also increased in population from foreign country of birth. There is an increase of the cases since 2016, probably due to the changes in the notification system, increasing the diagnosis of cutaneous leishmaniasis. Improvements in the current surveillance system are needed. Notification of the disease, vector, and reservoir control activities are also essential for the control of the disease.

Threats and Interventions During the Treatment of Tuberculosis in an Inner-city District / Factores de riesgo e intervenciones durante el tratamiento de la tuberculosis en un barrio marginal

Background: Since there are active drugs against tuberculosis (TB), the most effective control measures are to assure treatment adherence and to perform contact tracing. Given the long treatment duration and characteristics of some TB patients, threats that put at risk treatment adherence may appear. Identify and address them is essential to achieve the objectives of disease control.Objectives: To identify the epidemiological characteristics of TB patients and the incidents and threats occurring during treatment, to describe the interventions performed to enhance treatment adherence and to determine if there are differences among native and foreign-born patients in the TB clinical unit of a referral hospital in the inner city of Barcelona.Methods: A descriptive, observational, cross-sectional study was performed. We recorded information on sociodemographic and clinical characteristics, incidents and interventions during treatment in all patients with TB diagnosed between September 2013 and August 2016.Results: 172 patients were included, 62.2% were foreign-born. The most common incidents and threats were medication-related complications (43.0%), missed follow-up visits (34.3%), communication problems (25.6%), comorbidities complications (23.8%), trips (19.2%), fear of social rejection (16.9%) and change of address (14.5%). The adherence-promoting interventions were: follow-up calls, directly observed treatment, medical and humanitarian reports, extra visits and cultural mediation. Incidents and interventions were more frequent in foreign-born patients, however there were no differences in treatment success among Spanish and foreign-born. (AU)

Antecedentes: Dado que existen medicamentos activos contra la tuberculosis (TB), las medidas de control más efectivas son asegurar la adherencia al tratamiento y realizar un seguimiento cercano. Debido a la larga duración del tratamiento y las características de algunos pacientes con TB, pueden entrar en juego ciertos factores que hacen peligrar la adherencia al tratamiento. Identificar estos factores y abordarlos es esencial para lograr los objetivos de control de la enfermedad.Objetivos: Identificar las características epidemiológicas de los pacientes con TB y los incidentes y factores que tienen lugar durante el tratamiento, describir las intervenciones realizadas para mejorar la adherencia al tratamiento y determinar si existen diferencias entre los pacientes nativos y extranjeros en la Unidad Clínica de TB de un hospital de referencia en el centro de la ciudad de Barcelona.Métodos: Se realizó un estudio descriptivo, observacional y transversal. Registramos las características sociodemográficas y clínicas de todos los pacientes con TB diagnosticados entre septiembre de 2013 y agosto de 2016, así como los incidentes y las intervenciones realizadas durante el tratamiento.Resultados: Se incluyeron 172 pacientes, el 62,2% eran nacidos en el extranjero. Los incidentes y los factores de riesgo más comunes fueron: complicaciones relacionadas con la medicación (43,0%), visitas de seguimiento perdidas (34,3%), problemas de comunicación (25,6%), complicaciones de las comorbilidades (23,8%), viajes (19,2%), miedo al rechazo social (16,9%) y cambio de domicilio (14,5%). Las intervenciones para el fomento de la adherencia fueron: llamadas de seguimiento, tratamiento directamente observado, informes médicos y humanitarios, visitas adicionales y mediación cultural. Los incidentes e intervenciones fueron más frecuentes en pacientes nacidos en el extranjero; sin embargo, no hubo diferencias en el éxito del tratamiento entre españoles y nacidos en el extranjero. (AU)

Threats and Interventions During the Treatment of Tuberculosis in an Inner-city District.

BACKGROUND: Since there are active drugs against tuberculosis (TB), the most effective control measures are to assure treatment adherence and to perform contact tracing. Given the long treatment duration and characteristics of some TB patients, threats that put at risk treatment adherence may appear. Identify and address them is essential to achieve the objectives of disease control. OBJECTIVES: To identify the epidemiological characteristics of TB patients and the incidents and threats occurring during treatment, to describe the interventions performed to enhance treatment adherence and to determine if there are differences among native and foreign-born patients in the TB clinical unit of a referral hospital in the inner city of Barcelona. METHODS: A descriptive, observational, cross-sectional study was performed. We recorded information on sociodemographic and clinical characteristics, incidents and interventions during treatment in all patients with TB diagnosed between September 2013 and August 2016. RESULTS: 172 patients were included, 62.2% were foreign-born. The most common incidents and threats were medication-related complications (43.0%), missed follow-up visits (34.3%), communication problems (25.6%), comorbidities complications (23.8%), trips (19.2%), fear of social rejection (16.9%) and change of address (14.5%). The adherence-promoting interventions were: follow-up calls, directly observed treatment, medical and humanitarian reports, extra visits and cultural mediation. Incidents and interventions were more frequent in foreign-born patients, however there were no differences in treatment success among Spanish and foreign-born. CONCLUSION: In this inner city several incidents occurred during TB treatment that can threaten adherence and are more common among foreign-born patients. Coordination among professionals from different healthcare settings was able to overcome obstacles in most cases and achieve TB treatment completion.

Discovery and validation of an NMR-based metabolomic profile in urine as TB biomarker.

Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.

Correction: Epidemiology of Tuberculosis in Immigrants in a Large City with Large-Scale Immigration (1991-2013).

[This corrects the article DOI: 10.1371/journal.pone.0164736.].