Tuberculosis in young refugees Ritz, Nicole; Brinkmann, Folke; Garcia, Begoña Santiago ...
The Lancet (British edition),
12/2015, Volume:
386, Issue:
10012
Journal Article
Peer reviewed
Open access
The results showed that 86% of these countries had tuberculosis screening programmes for active tuberculosis and 55% of these countries had latent tuberculosis infection in refugees.3 The ptbnet--a ...clinical research network of more than 100 physicians in 24 European countries providing care for children with tuberculosis4,5--would like to express concerns that refugee children and adolescents are at risk of being neglected as a group if only symptom-based tuberculosis screening is used.
Non-tuberculous mycobacteria (NTM) are a large family of acid-fast bacteria, widespread in the environment. In children, NTM cause lymphadenitis, skin and soft tissue infections, and occasionally ...also lung disease and disseminated infections. These manifestations can be indistinguishable from tuberculosis on the basis of clinical and radiological findings and tuberculin skin testing. A diagnostic and therapeutic problem for respiratory physicians and other clinicians is therefore evident, particularly in settings where childhood tuberculosis is common, and bacteriological confirmation of any mycobacterial disease is difficult because of low availability of laboratory services in low-resource settings and the inherent paucibacillary nature of mycobacterial disease in childhood. The epidemiology of NTM varies by world region, and attempts to understand the burden of NTM disease and to identify risk factors in the paediatric population are hampered by inadequate mandatory NTM reporting and the overlap of clinical presentation with tuberculosis. The immune response to both NTM and Mycobacterium tuberculosis is based on cellular immunity and relies on the type-1 cytokine pathway. The disruption of this immune response by genetic or acquired mechanisms, such as mendelian susceptibility to mycobacterial disease or HIV, might result in predisposition to mycobacterial infections. Published diagnostic and management guidelines do not provide specific advice for diagnosis of NTM in children, from whom the quantity and quality of diagnostic samples are often suboptimum. Treatment of NTM infections is very different from the treatment of tuberculosis, depends on the strain and anatomical site of infection, and often involves antibiotic combinations, surgery, or both. In this Review, we summarise the epidemiological and clinical features of NTM infection in children, with a specific focus on the implications for public health in settings with a high endemic burden of childhood tuberculosis.
Tuberculosis (TB) poses a major public health challenge, particularly in children. A substantial proportion of children with TB disease remain undetected and unconfirmed. Therefore, there is an ...urgent need for a highly sensitive point-of-care test. This study aims to assess the performance of serological assays based on various antigen targets and antibody properties in distinguishing children (0-18 years) with TB disease (1) from healthy TB-exposed children, (2) children with non-TB lower respiratory tract infections, and (3) from children with TB infection.
The study will use biobanked plasma samples collected from three prospective multicentric diagnostic observational studies: the Childhood TB in Switzerland (CITRUS) study, the Pediatric TB Research Network in Spain (pTBred), and the Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infections in children and adolescents (ProPAED) study. Included are children diagnosed with TB disease or infection, healthy TB-exposed children, and sick children with non-TB lower respiratory tract infection. Serological multiplex assays will be performed to identify M. tuberculosis antigen-specific antibody features, including isotypes, subclasses, Fc receptor (FcR) binding, and IgG glycosylation.
The findings from this study will help to design serological assays for diagnosing TB disease in children. Importantly, those assays could easily be developed as low-cost point-of-care tests, thereby offering a potential solution for resource-constrained settings.
NCT03044509.
Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the ...changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time.
Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome.
Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, IQR 4.9-15.1), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674).
In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.
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.
Abstract
Background
It is known that SARS-CoV-2 antibodies from pregnant women with SARS-CoV-2 infection during pregnancy cross the placenta but the duration and the protective effect of these ...antibodies in infants is scarce.
Methods
This prospective study included mothers with SARS-COV-2 infection during pregnancy and their infants from April 2020 to March 2021. IgG antibodies to SARS-CoV-2 spike protein were performed on women and infants at birth and at two and six months during follow-up. Anthropometrical measures and physical and neurological examinations and a clinical history of symptoms and COVID-19 diagnosis were collected. Simple linear regression was performed to compare categorical and continuous variables. To compare the mother’s and infant’s antibody titers evolution, a mixed linear regression model was used. A predictive model of newborn antibody titers at birth has been established by means of simple stepwise linear regression.
Results
51 mother-infant couples were included. 45 (90%) of the mothers and 44 (86.3%) of the newborns had a positive serology al birth. These antibodies were progressively decreasing and were positive in 34 (66.7%) and 7 (13.7%) of infants at 2 and 6 months, respectively. IgG titers of newborns at birth were related to mothers’ titers, with a positive moderate correlation (Pearson’s correlation coefficient: 0.82, p < 0,001). Fetal/maternal antibodies placental transference rate was 1.3 (IQR: 0.7–2.2). The maternal IgG titers at delivery and the type of maternal infection (acute, recent, or past infection) was significantly related with infants’ antibody titers at birth. No other epidemiological or clinical factors were related to antibodies titers. Neurodevelopment, psychomotor development, and growth were normal in 94.2% of infants in the third follow-up visit. No infants had a COVID-19 diagnosis during the follow-up period.
Conclusions
Transplacental transfer of maternal antibodies is high in newborns from mothers with recent or past infection at delivery, but these antibodies decrease after the first months of life. Infant’s IgG titers were related to maternal IgG titers at delivery. Further studies are needed to learn about the protective role of maternal antibodies in infants.
We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with ...significant decreases in TB1 (-1.72
. -0.03 IU/ml, p=0.001) and TB2 (-1.65
. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0%
11.9%, p=0.042), and those with TST induration <15mm (29%
13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.
SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with ...SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.
BACKGROUND:In recent years, there is an increasing interest in the use of linezolid for the treatment of tuberculosis (TB).
METHODS:Patients less than 18 years of age who received linezolid within ...the Spanish Pediatric TB Network from 2001 to 2016 were retrospectively included. Treatment characteristics, adverse events (AEs) and outcomes were analyzed.
RESULTS:Fifteen children were included (53% male) with a median age of 3.6 years interquartile range (IQR)1.6–6.2. Median follow-up was 54 months (IQR38–76). The reasons for linezolid use were drug-resistant TB in 8 (53%) patients, drug-induced liver injury in 5 (33%) patients and chronic liver disease in 2 (13%) patients. Four children (26%) were on immunosuppressive therapy when TB was diagnosed. Five children (33%) were diagnosed with extrapulmonary TB. The median duration of linezolid treatment was 13 months (IQR7.5–17). Nine patients had 13 linezolid-related AEs. Hematologic toxicity was observed in 8 patients (53%) and gastrointestinal intolerance in 3 patients (20%). In 2 patients, linezolid dose was reduced, and in 2 patients, linezolid was discontinued because of AEs. A 2-year-old girl went back to her country of birth and was lost to follow-up. No relapses were observed among the other 14 patients (93%).
CONCLUSIONS:Linezolid may be considered when treating children with drug-resistant TB but also in the cases of patients with chronic liver disease or drug-induced liver injury. However, AEs should be closely monitored. Further studies are needed to determine the optimum dosage and the optimal duration of linezolid treatment in children.
BACKGROUND:Children are at higher risk of tuberculosis (TB) dissemination and extrapulmonary disease, contributing greatly to TB-associated morbidity and long-term sequelae. However, there are very ...few studies that assess the impact and clinical spectrum of pediatric extrapulmonary TB (EPTB) in low-prevalence regions.
METHODS:Children <18 years of age diagnosed with TB in Madrid region (2005–2013) were reviewed. We compared the epidemiology, clinical characteristics and the performance of diagnostic tests in childhood extrapulmonary and pulmonary disease. We performed a multivariate logistic regression to identify factors associated with EPTB.
RESULTS:During the study period, 93 of 526 pediatric TB cases had EPTB (17.7%). The most common site was lymphatic TB (34.5%). The source case was not identified in most extrapulmonary cases, contrary to pulmonary TB (28% vs. 63.3%; P < 0.001). The tuberculin-skin-test induration was smaller in EPTB cases (<5 mm 22% vs. 5%; P < 0.001), but the sensitivity of interferon-gamma-release-assays was similar (76.9% vs. 79.4%). Children with EPTB presented higher rate of bacteriologic confirmation (66% vs. 49.4%; P < 0.01), and higher incidence of multidrug resistant TB (8.2% vs. 1.6%; P = 0.03). Complications were present in 40.2% extrapulmonary cases. EPTB was associated with the childʼs foreign origin odds ratio (OR) 2.3 (1.1–5.3), immune disorders OR 5.8 (1.9–17.1) and drug resistance OR 2.4 (1.1–5.4).
CONCLUSIONS:In our low-prevalence region, childhood EPTB was linked to immigrant status, immune disorders and drug resistance, and presented high rate of complications. Our study underscores the relevance of improved diagnostic tools and systematic TB screening in high risk populations.
