Performance of QuantiFERON-TB Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study.

INTRODUCTION: The QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay's performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting. METHODS: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020. RESULTS: Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2-, n=2; TB1-/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations. CONCLUSIONS: Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay's performance substantially.

Diagnostic Accuracy of QuantiFERON-TB Gold Plus Assays in Children and Adolescents with Tuberculosis Disease.

In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We conducted a cross-sectional multicenter study, involving 158 children and adolescents with tuberculosis disease. The overall sensitivity of the assay was 82.9% (IQR 77.0%-88.8%), indicating that in children this test does not have higher sensitivity than previous generation interferon-gamma release assays.

Microscopic observation drug-susceptibility assay vs. Xpert® MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost-utility analysis.

OBJECTIVE: To compare the cost-utility of microscopic observation drug-susceptibility assay (MODS) and Xpert® MTB/RIF implementation for tuberculosis (TB) diagnosis in rural northern Mozambique. METHODS: Stochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and Xpert® MTB/RIF were evaluated as replacement test of smear microscopy (SM) or as an add-on test after a negative SM. Costs were calculated in 2013 USD, effects in disability-adjusted life years (DALY). Willingness to pay threshold (WPT) was established at once the per capita Gross National Income of Mozambique. RESULTS: MODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. Xpert® MTB/RIF as an add-on test to negative SM yielded ICER of 345.71USD/DALY averted. Xpert® MTB/RIF as a substitute for SM obtained an ICER of 122.13USD/DALY averted. TB prevalence and risk of infection were the main factors impacting MODS and Xpert® MTB/RIF ICER in the one-way sensitivity analysis. In the probabilistic sensitivity analysis, Xpert® MTB/RIF was most likely to have an ICER below the WPT, whereas MODS was not. CONCLUSION: Our cost-utility analysis favours the implementation of Xpert® MTB/RIF as a replacement of SM for all TB suspects in this rural high TB/HIV prevalence African setting.

Microscopic observation drug susceptibility assay for the diagnosis of TB and MDR-TB in HIV-infected patients: a systematic review and meta-analysis.

The objective of the present study was to assess the diagnostic accuracy of the microscopic observation drug susceptibility (MODS) assay for tuberculosis (TB) diagnosis in HIV-infected patients. MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials, African Index Medicus, ResearchGate, SciELO, and the abstracts of the main conferences on infectious diseases and tropical medicine were searched, and other sources investigated. Only studies including HIV-infected patients evaluating MODS for the diagnosis of TB and using culture-based diagnostic tests as a gold standard were analysed. Summary sensitivity and specificity were calculated with a bivariate model. 3259 citations were found, 29 were selected for full-text review and 10 studies including 3075 samples were finally analysed. Overall diagnostic accuracy of MODS for the diagnosis of TB was a sensitivity of 88.3% (95% CI 86.18-90.2%) and specificity 98.2% (95% CI 97.75-98.55%). For multidrug-resistant (MDR)-TB, sensitivity was 89% (95% CI 66.07-97%) and specificity was 100% (95 CI 94.81-100%). For smear-negative pulmonary TB, a sensitivity of 88.2% (95% CI 86.1-89.9%) and specificity of 98.2% (95% CI 96.8-98.9%) were found. Costs varied between USD 0.72 and 7.31 per sample. Mean time to positivity was 8.24 days. MODS was found to have a good accuracy for the diagnosis of TB and MDR-TB in HIV-infected patients with low cost and fast results.

Tuberculosis among children visiting friends & relatives.

BACKGROUND: Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR. METHODS: We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8-12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus. RESULTS: Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8-28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3-9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9-20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1-13.3). CONCLUSIONS: The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions.

Trends in child and adolescent mental health in Catalonia in the context of the COVID-19 pandemic during the 2020-2021 school year.

INTRODUCTION: The SARS-CoV-2 pandemic has had a great impact on the physical and psychological health of the population. The aim of this study was to evaluate child and adolescent mental health in a population cohort along the 2020-2021 school year. METHODS: This was a prospective longitudinal study of a cohort of children from 5-14 years of age in Catalonia, Spain, performed from September 2020 to July 2021. The participants were randomly selected and accompanied by their primary care paediatrician. Evaluation of risk of psychopathology was performed using the Strengths and Difficulties Questionnaire (SDQ) carried out by one of the legal guardians of the child. We also collected sociodemographic and health variables of the participants and their nuclear family. Data were collected by an online survey through the RedCap platform at the beginning of the academic year and at the end of each trimester (4 cuts). RESULTS: At the beginning of the school year, 9.8% of the patients were probable cases of psychopathology compared to 6.2% at the end of the year. The perception of the level of preoccupation of the children for their health and that of their family was related to presenting psychopathology, especially at the beginning of the year, with the perception of a good family atmosphere being always related to lower risk. No variable related to COVID-19 was associated with an altered SDQ result. CONCLUSIONS: Along the 2020-2021 school year, the percentage of children with a probability of presenting psychopathology decreased from 9.8% to 6.2%.

[Trends in child and adolescent mental health in Catalonia in the context of the covid-19 pandemic during the 2020-2021 school year]. / Evolución de la salud mental infanto-juvenil en Catalunya en el contexto de la pandemia por la COVID-19 durante el curso escolar 2020-2021.

Introduction: The SARS-CoV-2 pandemic has had a great impact on the physical and psychological health of the population. The aim of our study was to assess child and adolescent mental health in a cohort throughout the 2020-2021 school year. Methods: We conducted a longitudinal prospective study in a cohort of children aged 5 to 14 years in Catalonia, Spain, from September 2020 to July 2021. Participants were randomly selected and followed up by their primary care paediatricians. The risk of mental health problems was assessed with the Strengths and Difficulties Questionnaire (SDQ), completed by one of the legal guardians of the child. In addition, we obtained information on the sociodemographic and health characteristics of the participants and their nuclear families. We collected the data by means of an online survey through the REDCap platform at the beginning of the academic year and at the end of each term (4 time points). Results: At the beginning of the school year, 9.8% of participants were cases of probable psychopathology compared to 6.2% at the end of the year. The perceived level of worry of the children for their own health and the health of their families was associated with the presence of psychopathology, especially at the beginning of the year, while the perception of a good family atmosphere was consistently associated with a decreased risk. No variable related to COVID-19 was associated with abnormal results in the SDQ. Conclusions: During the 2020-2021 school year, the percentage of children with probable psychopathology decreased from 9.8% to 6.2%.

The Value of the Second QuantiFERON-TB Gold-Plus Antigen Tube at Diagnosis and at Treatment Completion in Spanish Children With Tuberculosis.

We studied 295 children (tuberculosis disease, n = 159; latent tuberculosis infection, n = 136) with positive QuantiFERON-TB Gold-Plus assay results. No significant differences between first and second antigen tube interferon-gamma responses were detected, irrespective of patient and disease characteristics at diagnosis. Of patients with a repeat assay after treatment completion (n = 65), only 16.9% converted to negative results.

State of child and adolescent mental health during the first wave of the COVID-19 pandemic and at the beginning of the 2020-2021 school year.

INTRODUCTION: The aim of this project was to evaluate the psychopathological impact of home confinement and school closing between March and September 2020 on the mental health of Catalonian children. METHODS: PEDSAME study: first cross-sectional section (beginning of the school year) and retrospective data (lockdown), carried out through the network of Primary Care pediatricians in the Catalan population between 5 and 14 years (included) from 09/14/2020 to 10/30/2020 in a random sample. Data were collected with an online survey through the RedCap platform at the beginning of the school year. The main variable was the result of the Strengths and Difficulties Questionnaire answered by parents to assess the risk of psychopathology, in addition to other related variable. RESULTS: The results obtained at the beginning of the school year show that 9.8% of the patients were probable cases of psychopathology. The most affected group were those between 5 and 8 years. The perception of the children's level of concern for their health and that of their family was a risk factor for presenting psychopathology, while the good family environment was a protective factor. Emotional and behavioral symptoms, sleep disorders and problematic use of screens were detected more frequently during confinement than at the beginning of the school year. CONCLUSIONS: Confinement and the absence of schooling for 6 months had a negative impact on the mental health of the child-adolescent population who showed worse indicators than the previous year.

[State of child and adolescent mental health during the first wave of the COVID-19 pandemic and at the beginning of the 2020-2021 school year]. / Estado de la salud mental infantojuvenil durante la primera ola de la pandemia de la COVID-19 y en el inicio del curso escolar 2020-2021.

INTRODUCTION: The aim of this project was to evaluate the psychopathological impact of home confinement and school closing between March and September 2020 on the mental health of Catalonian children. METHODS: PEDSAME study: first cross-sectional section (beginning of the school year) and retrospective data (lockdown), carried out through the network of Primary Care pediatricians in the Catalan population between 5 and 14 years (included) from 09/14/2020 to 10/30/2020 in a random sample. Data were collected with an online survey through the RedCap platform at the beginning of the school year. The main variable was the result of the Strengths and Difficulties Questionnaire answered by parents to assess the risk of psychopathology, in addition to other related variable. RESULTS: The results obtained at the beginning of the school year show that 9.8% of the patients were probable cases of psychopathology. The most affected group were those between 5 and 8 years. The perception of the children's level of concern for their health and that of their family was a risk factor for presenting psychopathology, while the good family environment was a protective factor. Emotional and behavioral symptoms, sleep disorders and problematic use of screens were detected more frequently during confinement than at the beginning of the school year. CONCLUSIONS: Confinement and the absence of schooling for 6 months had a negative impact on the mental health of the child-adolescent population who showed worse indicators than the previous year.

QuantiFERON-TB Gold Plus Assay Specificity in Children and Adolescents With Suspected Tuberculosis-A Multicenter Cross-sectional Study in Spain.

In this cross-sectional study of 284 children and adolescents with clinically or radiologically suspected tuberculosis in a low-endemic country, the QuantiFERON-TB Gold Plus assay specificity, sensitivity, positive predictive value and negative predictive value were 91.5%, 87.3%, 86.4%, and 91.2%, respectively. The specificity was higher than that observed in tuberculin skin tests performed simultaneously, but similar to previous-generation interferon-gamma release assays.

Urine NMR-based TB metabolic fingerprinting for the diagnosis of TB in children.

Tuberculosis (TB) is a major cause of morbidity and mortality in children, and early diagnosis and treatment are crucial to reduce long-term morbidity and mortality. In this study, we explore whether urine nuclear magnetic resonance (NMR)-based metabolomics could be used to identify differences in the metabolic response of children with different diagnostic certainty of TB. We included 62 children with signs and symptoms of TB and 55 apparently healthy children. Six of the children with presumptive TB had bacteriologically confirmed TB, 52 children with unconfirmed TB, and 4 children with unlikely TB. Urine metabolic fingerprints were identified using high- and low-field proton NMR platforms and assessed with pattern recognition techniques such as principal components analysis and partial least squares discriminant analysis. We observed differences in the metabolic fingerprint of children with bacteriologically confirmed and unconfirmed TB compared to children with unlikely TB (p = 0.041 and p = 0.013, respectively). Moreover, children with unconfirmed TB with X-rays compatible with TB showed differences in the metabolic fingerprint compared to children with non-pathological X-rays (p = 0.009). Differences in the metabolic fingerprint in children with different diagnostic certainty of TB could contribute to a more accurate characterisation of TB in the paediatric population. The use of metabolomics could be useful to improve the prediction of TB progression and diagnosis in children.

Diagnostic Performance of the Fujifilm SILVAMP TB-LAM in Children with Presumptive Tuberculosis.

Current diagnostics for tuberculosis (TB) only manage to confirm a small proportion of children with TB and require respiratory samples, which are difficult to obtain. There is a need for non-invasive biomarker-based tests as an alternative to sputum testing. Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM), a lateral-flow test to detect lipoarabinomannan in urine, is a novel non-sputum-based point-of-care diagnostic reported to have increased sensitivity for the diagnosis of TB among human immunodeficiency virus (HIV)-infected adults. We evaluate the performance of FujiLAM in children with presumptive TB. Fifty-nine children attending a paediatric hospital in Haiti with compatible signs and symptoms of TB were examined using Xpert MTB/RIF, smear microscopy and X-rays, and classified according to the certainty of diagnosis into bacteriologically confirmed TB (n = 5), unconfirmed TB (bacteriologically negative, n = 50) and unlikely TB (n = 4). Healthy children (n = 20) were enrolled as controls. FujiLAM sensitivity and specificity were 60% and 95% among children with confirmed TB. FujiLAM's high specificity and its characteristics as a point-of-care indicate the test has a good potential for the diagnosis of TB in children.

Risk Factors for COVID-19 Morbidity and Mortality in Institutionalised Elderly People.

BACKGROUND: SARS-CoV-2 has caused a high mortality in institutionalised individuals. There are very few studies on the involvement and the real impact of COVID-19 in nursing homes. This study analysed factors related to morbidity and mortality of COVID-19 in institutionalised elderly people. METHODS: This cohort study included 842 individuals from 12 nursing homes in Sant Cugat del Vallès (Spain) from 15 March to 15 May 2020. We evaluated individual factors (demographic, dependence, clinical, and therapeutic) and those related to the nursing homes (size and staff) associated with infection and mortality by SARS-CoV-2. Infection was diagnosed by molecular biology test. RESULTS: Of the 842 residents included in the analysis, 784 underwent a Polymerase Chain Reaction (PCR) test; 74.2% were women, the mean age was 87.1 years, and 11.1% died. The PCR test was positive in 44%. A total of 33.4% of the residents presented symptoms compatible with COVID-19 and of these, 80.9% were PCR-positive for SARS-CoV-2. Infection by SARS-CoV-2 among residents was associated with the rate of staff infected in the homes. Mortality by SARS-CoV-2 was related to male sex and a greater grade of dependence measured with the Barthel index. CONCLUSIONS: SARS-Cov-2 infection in institutionalised people is associated with the infection rate in nursing home workers and mortality by SARS-Cov-2 with sex and greater dependency according to the Barthel index. Adequate management of nursing home staff and special attention to measures of infection control, especially of individuals with greater dependence, are keys for successful management of future pandemic situations.

Tuberculosis infection in children visiting friends and relatives in countries with high incidence of tuberculosis: A study protocol.

INTRODUCTION: Tuberculosis (TB) is a global infectious disease. In low-incidence countries, paediatric TB affects mostly immigrant children and children of immigrants. We hypothesize that these children are at risk of exposure to Mycobacterium tuberculosis when they travel to the country of origin of their parents to visit friends and relatives (VFR). In this study, we aim to estimate the incidence rate and risk factors associated to latent tuberculosis infection (LTBI) and TB in VFR children. METHODS AND ANALYSIS: A prospective study will be carried out in collaboration with 21 primary health care centres (PCC) and 5 hospitals in Catalonia, Spain. The study participants are children under 15 years of age, either immigrant themselves or born to immigrant parents, who travel to countries with high incidence of TB (≥ 40 cases/100,000 inhabitants). A sample size of 492 children was calculated. Participants will be recruited before traveling, either during a visit to a travel clinic or to their PCC, where a questionnaire including sociodemographic, epidemiological and clinical data will be completed, and a tuberculin skin test (TST) will be performed and read after 48 to 72 hours; patients with a positive TST at baseline will be excluded. A visit will be scheduled eight to twelve-weeks after their return to perform a TST and a QuantiFERON-TB Gold Plus test. The incidence rate of LTBI will be estimated per individual/month and person/year per country visited, and also by age-group. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Ethics Committee of the Hospital Universitari Mútua Terrassa (code 02/16) and the Clinical Research Ethics Committee of the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (code P16/094). Articles will be published in indexed scientific journals. TRIAL REGISTRATION: Clinical-Trials.gov: NCT04236765.

Paromomycin is superior to metronidazole in Dientamoeba fragilis treatment.

Dientamoeba fragilis is a trichomonad parasite of the human intestine that is found worldwide. However, the biological cycle and transmission of this parasite have yet to be elucidated. Although its pathogenic capacity has been questioned, there is increasing evidence that clinical manifestations vary greatly. Different therapeutic options with antiparasitic drugs are currently available; however, very few studies have compared the effectiveness of these drugs. In the present longitudinal study, we evaluate 13,983 copro-parasitological studies using light microscopy of stools, during 2013-2015, in Terrassa, Barcelona (Spain). A total of 1150 (8.2%) presented D. fragilis. Of these, 739 episodes were finally analyzed: those that involved a follow-up parasitology test up to 3 months later, corresponding to 586 patients with gastrointestinal symptoms (53% under 15 years of age). Coinfection by Blastocystis hominis was present in 33.6% of the subjects. Our aim was to compare therapeutic responses to different antiparasitic drugs and the factors associated with the persistence of D. fragilis post-treatment. Gender, age, and other intestinal parasitic coinfections were not associated with parasite persistence following treatment. Metronidazole was the therapeutic option in most cases, followed by paromomycin: 65.4% and 17.5% respectively. Paromomycin was found to be more effective at eradicating parasitic infection than metronidazole (81.8% vs. 65.4%; p = 0.007), except in children under six years of age (p = 0.538). Although Dientamoeba fragilis mainly produces mild clinical manifestations, the high burden of infection means we require better understanding of its epidemiological cycle and pathogenicity, as well as adequate therapeutic guidelines in order to adapt medical care and policies to respond to this health problem.

A Model Based on the Combination of IFN-γ, IP-10, Ferritin and 25-Hydroxyvitamin D for Discriminating Latent From Active Tuberculosis in Children.

In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Toxocara canis Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91-1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children.

Clinical Presentations and Outcomes Related to Tuberculosis in Children Younger Than 2 Years of Age in Catalonia.

Introduction: Children younger than 2 years have an increased risk of complications associated with tuberculosis (TB) due to the immaturity of the innate and adaptive immune response. We aimed to identify TB clinical presentations and outcomes as well as risk factors for complications in this age group. Materials and Methods: Multicenter, retrospective, cross-sectional study of TB cases in children aged <2 years in Catalonia (2005-2013). Epidemiological and clinical data were collected from the hospital medical records. TB complications, sequelae included, were defined as any tissue damage generating functional or anatomical impairment after being diagnosed or after TB treatment being completed. Statistical analyses were based on bivariate chi-square and multivariate logistic regression, and it was carried out with Stata® version 13.1. Odds ratios (OR) and its 95% confidence intervals were calculated (CI). Results: A total of 134 patients were included, 50.7% were male, the median [IQR] age was 13[8-18] months, and 18.7% (25/134) showed TB-associated complications. Pulmonary TB was diagnosed in 94.0% (126/134) of children, and the most common complications were lobar collapse (6/126). TB meningitis was diagnosed in 14/134 (10.4%), and hydrocephalus and mental impairment occurred in 1 and 2 patients, respectively. Two patients with spinal TB developed vertebral destruction and paraplegia, respectively. Only one of the patients died. At multivariate level, tachypnea (OR = 4.24; 95% CI 1.17-15.35) and meningeal (OR = 52.21; 95% CI 10.05-271.2) or combined/extrapulmonary forms (OR = 11.3; 95% CI 2.85-45.1) were associated with the development of TB complications. Discussion: TB complications are common in children under 2 years old. Extrapulmonary TB forms in this pediatric age remain a challenge and require prompt diagnosis and treatment in order to prevent them. The presence of tachypnea at the time of TB diagnosis is an independent associated factor to the development of TB complications in infants. This clinical sign should be closely monitored in patients in this age group. It is necessary to perform further studies in this age group in a prospective design in order to understand whether there are other factors associated to TB complications.

Epidemiology of Otitis Media with Spontaneous Perforation of the Tympanic Membrane in Young Children and Association with Bacterial Nasopharyngeal Carriage, Recurrences and Pneumococcal Vaccination in Catalonia, Spain - The Prospective HERMES Study.

The Epidemiology of otitis media with spontaneous perforation of the tympanic membrane and associated nasopharyngeal carriage of bacterial otopathogens was analysed in a county in Catalonia (Spain) with pneumococcal conjugate vaccines (PCVs) not included in the immunization programme at study time. A prospective, multicentre study was performed in 10 primary care centres and 2 hospitals (June 2011-June 2014), including all otherwise healthy children ≥2 months ≤8 years with otitis media presenting spontaneous tympanic perforation within 48h. Up to 521 otitis episodes in 487 children were included, showing by culture/PCR in middle ear fluid (MEF): Haemophilus influenzae [24.2%], both Streptococcus pneumoniae and H. influenzae [24.0%], S. pneumoniae [15.9%], Streptococcus pyogenes [13.6%], and Staphylococcus aureus [6.7%]. Culture-negative/PCR-positive otitis accounted for 31.3% (S. pneumoniae), 30.2% (H. influenzae) and 89.6% (mixed S. pneumoniae/H. influenzae infections). Overall, incidence decreased over the 3-year study period, with significant decreases in otitis by S. pneumoniae and by H. influenzae, but no decreases for mixed S. pneumoniae/H. influenzae infections. Concordance between species in nasopharynx and MEF was found in 58.3% of cases, with maximal rates for S. pyogenes (71.8%), and with identical pneumococcal serotype in 40.5% of cases. Most patients (66.6%) had past episodes. PCV13 serotypes were significantly more frequent in first episodes, in otitis by S. pneumoniae as single agent, and among MEF than nasopharyngeal isolates. All non-PCV13 serotypes separately accounted for <5% in MEF. Up to 73.9% children had received ≥1 dose of PCV, with lower carriage of PCV13 serotypes than among non-vaccinated children. Pooling pneumococcal isolates from MEF and nasopharynx, 30% were multidrug resistant, primarily belonging to serotypes 19A [29.8%], 24A [14.3%], 19F [8.3%] and 15A [6.0%]. Our results suggest that increasing PCV13 vaccination would further reduce transmission of PCV13 serotypes with special benefits for youngest children (with none or uncompleted vaccine schedules), preventing first otitis episodes and subsequent recurrences.

Prevalence and Diagnosis of Latent Tuberculosis Infection in Young Children in the Absence of a Gold Standard.

INTRODUCTION: For adequate disease control the World Health Organization has proposed the diagnosis and treatment of latent tuberculous infection (LTBI) in groups of risk of developing the disease such as children. There is no gold standard (GS) test for the diagnosis of LTBI. The objective of this study was to estimate the prevalence of LTBI in young children in contact with a household case of tuberculosis (TB-HCC) and determine the accuracy and precision of the Tuberculin Skin Test (TST) and QuantiFERON-TB Gold in-tube (QFT) used in the absence of a GS. METHODS: We conducted a cross-sectional study in children up to 6 years of age in Manaus/Brazil during the years 2009-2010. All the children had been vaccinated with the BCG and were classified into two groups according to the presence of a TB-HCC or no known contact with tuberculosis (TB). The variables studied were: the TST and QFT results and the intensity and length of exposure to the index tuberculosis case. We used the latent class model to determine the prevalence of LTBI and the accuracy of the tests. RESULTS: Fifty percent of the children with TB-HCC had LTBI, with the prevalence depending on the intensity and length of exposure to the index case. The sensitivity and specificity of TST were 73% [95% confidence interval (CI): 53-91] and 97% (95%CI: 89-100), respectively, versus 53% (95%CI: 41-66) and 81% (95%CI:71-90) for QFT. The positive predictive value of TST in children with TB-HCC was 91% (95%CI: 61-99), being 74% for QFT (95%CI: 47-95). CONCLUSIONS: This is one of the first studies to estimate the prevalence of LTBI in children and the parameters of the main diagnostic tests using a latent class model. Our results suggest that children in contact with an index case have a high risk of infection. The accuracy and the predictive value of the two tests did not significantly differ. Combined use of the two tests showed scarce improvement in the diagnosis of LTBI.