RESUMO
BACKGROUND: Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs. METHODS: We conducted a prospective cohort study including 100 children aged <10â years with rRTIs, their family members, and healthy healthcare professionals. Total and polyreactive antibody concentrations were determined in serum and saliva (ELISA); respiratory microbiota composition (16S-rRNA-sequencing) and respiratory viruses (qPCR) were characterised in nasopharyngeal swabs. Proteomic analysis (Olink®) was performed on saliva and serum samples. RTI symptoms were monitored with a daily cell phone application and assessed using latent class analysis and negative binomial mixed models. RESULTS: Serum antibody levels were not associated with RTI severity. Strikingly, 28% of salivary antibodies and only 2% of serum antibodies displayed polyreactivity (p<0.001). Salivary polyreactive immunoglobulin A (IgA) was negatively associated with recurrent lower RTIs (aOR 0.80 [95% CI 0.67-0.94]) and detection of multiple respiratory viruses (aOR 0.76 [95% CI 0.61-0.96]). Haemophilus influenzae abundance was positively associated with RTI symptom burden (regression coefficient 0.07 [95% CI 0.02-0.12]). CONCLUSION: These results highlight the importance of mucosal immunity in RTI severity and burden and suggest that the level of salivary polyreactive IgA and H. influenzae abundance may serve as indicators of infection risk and severity in young children with rRTIs.
RESUMO
PURPOSE OF REVIEW: Lower respiratory tract infections (LRTIs) are an important cause of child morbidity and mortality globally, especially in children under the age of 5 years in Africa. Respiratory viruses, including human adenoviruses (HAdVs), are common causes of LRTIs in children. This review aims to shed light on the epidemiology, clinical manifestations, sequelae, and treatment options specific to adenovirus respiratory infections in African children. RECENT FINDINGS: Recent evidence has challenged the perception that adenovirus is a negligible cause of LRTIs. Studies show HAdV emerging as the third most common viral pathogen in fatal pneumonias among under-5 children in low-income and middle-income African countries, contributing to 5.5% of all pneumonia deaths and ranking second in hospital-associated viral pneumonia deaths. Predominant HAdV serotypes associated with disease differ by country and region, and have changed over time. Risk factors for increased disease severity and long-term respiratory sequelae in previously healthy African children with HAdV LRTIs are not well established. SUMMARY: Although respiratory viruses, including HAdV, are recognized contributors to LRTIs, the prevalence and impact of adenovirus infections have been under-recognized and understated. Available data suggests that African children, particularly those under 5âyears old, are at risk of severe sequelae from respiratory HAdV infections. Long-term sequelae, including bronchiectasis and postinfectious bronchiolitis obliterans, further underscore the significant impact of HAdV infections. However, the scarcity of comprehensive data hampers our understanding of the extent of the impact of HAdV infections on child lung health in Africa. We recommend scaled-up HAdV surveillance, ensuring its consistent inclusion in population-level LRTI assessments, and expanded and equitable access to diagnostics for early recognition of African children at risk of developing chronic sequelae and death. Enhanced understanding of adenovirus epidemiology and clinical outcomes and the availability of therapeutic options are essential for informed public health strategies and clinical care.
Assuntos
Infecções por Adenovirus Humanos , Infecções Respiratórias , Humanos , África/epidemiologia , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/terapia , Pré-Escolar , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/terapia , Adenovírus Humanos/patogenicidade , Lactente , Fatores de Risco , Prevalência , CriançaRESUMO
Immunological problems are increasingly acknowledged manifestations in many inherited metabolic diseases (IMDs), ranging from exaggerated inflammation, autoimmunity and abnormal cell counts to recurrent microbial infections. A subgroup of IMDs, the congenital disorders of glycosylation (CDG), includes CDG types that are even classified as primary immunodeficiencies. Here, we reviewed the list of metabolic disorders reported to be associated with various immunological defects and identified 171 IMDs accompanied by immunological manifestations. Most IMDs are accompanied by immune dysfunctions of which immunodeficiency and infections, innate immune defects, and autoimmunity are the most common abnormalities reported in 144/171 (84%), 44/171 (26%) and 33/171 (19%) of IMDs with immune system involvement, respectively, followed by autoinflammation 17/171 (10%). This article belongs to a series aiming at creating and maintaining a comprehensive list of clinical and metabolic differential diagnoses according to organ system involvement.
Assuntos
Doenças Metabólicas , Humanos , Doenças Metabólicas/genética , Glicosilação , InflamaçãoRESUMO
BACKGROUND: Recurrent respiratory tract infections (rRTIs) frequently affect young children and are associated with antibody deficiencies. We investigated the prevalence of and epidemiological risk factors associated with antibody deficiencies in young children with rRTIs and their progression over time, and linked these to prospectively measured RTI symptoms. METHODS: We included children <7 years with rRTIs in a prospective cohort study. Patient characteristics associated with antibody deficiencies were identified using multivariable logistic regression analysis. RESULTS: We included 146 children with a median age of 3.1 years. Daily RTI symptoms were monitored in winter in n = 73 children and repeated immunoglobulin level measurements were performed in n = 45 children. Antibody deficiency was diagnosed in 56% and associated with prematurity (OR 3.17 [1.15-10.29]) and a family history of rRTIs (OR 2.37 [1.11-5.15]). Respiratory symptoms did not differ between children with and without antibody deficiencies. During follow-up, antibody deficiency diagnosis remained unchanged in 67%, while 18% of children progressed to a more severe phenotype. CONCLUSION: Immune maturation and genetic predisposition may lie at the basis of antibody deficiencies commonly observed in early life. Because disease severity did not differ between children with and without antibody deficiency, we suggest symptom management can be similar for all children with rRTIs. IMPACT: An antibody deficiency was present in 56% of children <7 years with recurrent respiratory tract infections (rRTIs) in a Dutch tertiary hospital setting. Prematurity and a family history of rRTIs were associated with antibody deficiencies, suggesting that immune maturation and genetic predisposition may lie at the basis of antibody deficiencies in early life. RTI symptoms did not differ between children with and without antibody deficiency, suggesting that symptom management can be similar for all children with rRTIs, irrespective of humoral immunological deficiencies. During follow-up, 18% of children progressed to a more severe phenotype, emphasizing that early diagnosis is warranted to prevent long-term morbidity and increase quality of life.
Assuntos
Doenças da Imunodeficiência Primária , Infecções Respiratórias , Humanos , Criança , Pré-Escolar , Qualidade de Vida , Estudos Prospectivos , Predisposição Genética para Doença , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologiaRESUMO
BACKGROUND: Nasopharyngeal swabs are taken to determine the causative agent of community acquired pneumonia (CAP), while the reliability of upper respiratory tract sampling as a proxy for lower respiratory tract infections is still unclear. METHODS: Nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid samples and clinical data were collected from 153 hospitalized children between 3 months and 14 years of age with severe CAP, enrolled from March to June 2019. Written informed consent for the storage and use of the samples for further studies was obtained from the parents or caregivers. Putative pathogens were detected using a sensitive, high-throughput GeXP-based multiplex PCR and qPCR. RESULTS: The same bacterial species in paired samples were found in 29 (23.4%) and the same viral species in 52 (27.5%) of the patients. moderate concordance was found for Mycoplasma pneumoniae (ĸ=0.64), followed by Haemophilus influenzae (ĸ=0.42). The strongest discordance was observed for human adenovirus and also for Pseudomonas aeruginosa, the latter was exclusively detected in BAL samples. In the adenovirus cases strong concordance was associated with high viral loads in the NP swabs. CONCLUSION: The variation in concordance in pathogen detection in the upper and lower respiratory tract of children with severe pneumonia is generally high but varies depending on the species. Novel and impactful insights are the concordance between NP and BAL detection for M. pneumoniae and H. influenzae and the strong correlation between high adenoviral loads in NP swabs and detection in BAL fluid.
Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Infecções Respiratórias , Criança , Humanos , Lactente , Reprodutibilidade dos Testes , Bactérias/genética , Pneumonia/diagnóstico , Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Respiratórias/diagnóstico , Mycoplasma pneumoniae , Haemophilus influenzae , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , TraqueiaRESUMO
PURPOSE OF REVIEW: The respiratory microbiota has a role in respiratory tract infection (RTI) pathogenesis. On the mucosa, the respiratory microbiota interacts with potential pathogenic viruses, bacteria and the host immune system, including secretory IgA (sIgA). This review discusses the role of the respiratory microbiota and its interaction with the (mucosal) immune system in RTI susceptibility, as well as the potential to exploit the microbiota to promote health and prevent RTIs. RECENT FINDINGS: Recent studies confirm that specific microbiota profiles are associated with RTI susceptibility and during susceptibility and found accompanying RTIs, although clear associations have not yet been found for SARS-CoV-2 infection. sIgA plays a central role in RTI pathogenesis: it stands under control of the local microbiota, while at the same time influencing bacterial gene expression, metabolism and defense mechanisms. Respiratory microbiota interventions are still newly emerging but promising candidates for probiotics to prevent RTIs, such as Corynebacterium and Dolosigranulum species, have been identified. SUMMARY: Improved understanding of the respiratory microbiota in RTIs and its interplay with the immune system is of importance for early identification and follow-up of individuals at risk of infection. It also opens doors for future microbiota interventions by altering the microbiota towards a healthier state to prevent and/or adjunctively treat RTIs.
Assuntos
COVID-19 , Microbiota , Infecções Respiratórias , Bactérias/genética , Promoção da Saúde , Humanos , Imunoglobulina A Secretora , Infecções Respiratórias/prevenção & controle , SARS-CoV-2RESUMO
BACKGROUND: Many studies support the protective effect of breastfeeding on respiratory tract infections. Although infant formulas have been developed to provide adequate nutritional solutions, many components in human milk contributing to the protection of newborns and aiding immune development still need to be identified. In this paper we present the methodology of the "Protecting against Respiratory tract lnfections through human Milk Analysis" (PRIMA) cohort, which is an observational, prospective and multi-centre birth cohort aiming to identify novel functions of components in human milk that are protective against respiratory tract infections and allergic diseases early in life. METHODS: For the PRIMA human milk cohort we aim to recruit 1000 mother-child pairs in the first month postpartum. At one week, one, three, and six months after birth, fresh human milk samples will be collected and processed. In order to identify protective components, the level of pathogen specific antibodies, T cell composition, Human milk oligosaccharides, as well as extracellular vesicles (EVs) will be analysed, in the milk samples in relation to clinical data which are collected using two-weekly parental questionnaires. The primary outcome of this study is the number of parent-reported medically attended respiratory infections. Secondary outcomes that will be measured are physician diagnosed (respiratory) infections and allergies during the first year of life. DISCUSSION: The PRIMA human milk cohort will be a large prospective healthy birth cohort in which we will use an integrated, multidisciplinary approach to identify the longitudinal effect human milk components that play a role in preventing (respiratory) infections and allergies during the first year of life. Ultimately, we believe that this study will provide novel insights into immunomodulatory components in human milk. This may allow for optimizing formula feeding for all non-breastfed infants.
Assuntos
Hipersensibilidade , Infecções Respiratórias , Coorte de Nascimento , Aleitamento Materno , Feminino , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/prevenção & controle , Lactente , Recém-Nascido , Leite Humano , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controleRESUMO
BACKGROUND: Within Europe, the Netherlands has one of the lowest antibiotic consumption rates. We aimed to gain insight into attitudes of Dutch physicians and parents towards information provided during discharge conversations in the emergency department (ED) and towards antibiotic use in children, in order to obtain information on the assumptions and beliefs that underlie a practice of low prescription rates. METHODS: Discharge conversations of 70 children presenting with an infectious disease at the ED were observed. After 7-10 days, 55 parents were called for a semi-structured interview. In addition, 29 pediatricians and pediatric residents completed a questionnaire on their prescription behaviour. RESULTS: Concerns about (recognizing) the severity of their child's infection was parents' main motivation to seek help. Both pediatricians and parents reported a general reluctance towards antibiotic use. While pediatricians took appropriateness based on indication and the risk of antimicrobial resistance development into account when considering antibiotic treatment, a thorough medical assessment was deemed more important for Dutch parents than any type of therapeutic treatment, including antibiotics. The topic most often discussed during the discharge conversations was safety netting instructions (in 86%), which were discussed more often during discharge conversations with parents of children that did not receive antibiotic treatment (91% versus 69%). CONCLUSION: Dutch pediatricians and parents are both reluctant to use antibiotics for uncomplicated infections in children, but for different reasons. The emphasis of discharge conversations was on safety netting instructions, which seems to be an alternative for (early) antibiotic use in our setting and may guide overuse prevention strategies in settings where antibiotic overuse is more common.
Assuntos
Antibacterianos , Médicos , Antibacterianos/uso terapêutico , Criança , Serviço Hospitalar de Emergência , Humanos , Pais , Alta do Paciente , PrescriçõesRESUMO
BACKGROUND: Recent research suggests that the microbiota affects susceptibility to both respiratory tract infections (RTIs) and gastrointestinal infections (GIIs). In order to optimize global treatment options, it is important to characterize microbiota profiles across different niches and geographic/socioeconomic areas where RTI and GII prevalences are high. METHODS: We performed 16S sequencing of nasopharyngeal swabs from 209 Venezuelan Amerindian children aged 6 weeks-59 months who were participating in a 13-valent pneumococcal conjugate vaccine (PCV13) study. Using random forest models, differential abundance testing, and regression analysis, we determined whether specific bacteria were associated with RTIs or GIIs and variation in PCV13 response. RESULTS: Microbiota compositions differed between children with or without RTIs (P = .018) or GIIs (P = .001). Several species were associated with the absence of infections. Some of these health-associated bacteria are also observed in developed regions, such as Corynebacterium (log2(fold change [FC]) = 3.30 for RTIs and log2(FC) = 1.71 for GIIs), while others are not commonly observed in developed regions, such as Acinetobacter (log2(FC) = 2.82 and log2(FC) = 5.06, respectively). Klebsiella spp. presence was associated with both RTIs (log2(FC) = 5.48) and GIIs (log2(FC) = 7.20). CONCLUSIONS: The nasopharyngeal microbiota of rural Venezuelan children included several bacteria that thrive in tropical humid climates. Interestingly, nasopharyngeal microbiota composition not only differed in children with an RTI but also in those with a GII, which suggests a reciprocal interplay between the 2 environments. Knowledge of region-specific microbiota patterns enables tailoring of preventive and therapeutic approaches.
Assuntos
Doenças Transmissíveis , Microbiota , Infecções Pneumocócicas , Infecções Respiratórias , Bactérias/genética , Criança , Humanos , Lactente , Recém-Nascido , Nasofaringe , Vacinas Pneumocócicas , Infecções Respiratórias/epidemiologiaRESUMO
BACKGROUND: Children seem relatively protected from serious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease, but little is known about children living in settings with high tuberculosis and human immunodeficiency virus (HIV) burden. This study reflects clinical data on South African children with SARS-CoV-2. METHODS: We collected clinical data of children aged <13 years with laboratory-confirmed SARS-CoV-2 presenting to Tygerberg Hospital, Cape Town, between 17 April and 24 July 2020. RESULTS: One hundred fifty-nine children (median age, 48.0 months [interquartile range {IQR}, 12.0-106.0 months]) were included. Hospitalized children (nâ =â 62), with a median age of 13.5 months (IQR, 1.8-43.5 months) were younger than children not admitted (nâ =â 97; median age, 81.0 months [IQR, 34.5-120.5 months]; Pâ <â .01.). Thirty-three of 159 (20.8%) children had preexisting medical conditions. Fifty-one of 62 (82.3%) hospitalized children were symptomatic; lower respiratory tract infection was diagnosed in 21 of 51 (41.2%) children, and in 11 of 16 (68.8%) children <3 months of age. Respiratory support was required in 25 of 51 (49.0%) children; 13 of these (52.0%) were <3 months of age. One child was HIV infected and 11 of 51 (21.2%) were HIV exposed but uninfected, and 7 of 51 (13.7%) children had a recent or new diagnosis of tuberculosis. CONCLUSIONS: Children <1 year of age hospitalized with SARS-CoV-2 in Cape Town frequently required respiratory support. Access to oxygen may be limited in some low- and middle-income countries, which could potentially drive morbidity and mortality. HIV infection was uncommon but a relationship between HIV exposure, tuberculosis, and SARS-CoV-2 should be explored.
Assuntos
COVID-19 , Infecções por HIV , Criança , Pré-Escolar , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hospitais , Humanos , Lactente , SARS-CoV-2 , África do Sul/epidemiologiaRESUMO
Glucose transporter type 1 deficiency syndrome (GLUT1DS) is characterised by deficient glucose transport over the blood-brain barrier and reduced glucose availability in the brain. This causes epilepsy, movement disorders, and cognitive impairment. Treatment with ketogenic diet provides ketones as alternative energy source. However, not all GLUT1DS patients are on dietary treatment (worldwide registry: 77/181 [43%] of patients). The current 25-year experience allows evaluation of effects and tolerability of dietary treatment for GLUT1DS. To this end, literature was searched up to January 2019 for individual case reports and series reporting (side) effects of dietary treatment for GLUT1DS. Upon aggregation of data for analysis, we identified 270 GLUT1DS patients with dietary treatment with a mean follow-up of 53 months. Epilepsy improved for 83% of 230 patients and remained unchanged for 17%, movement disorders improved for 82% of 127 patients and remained unchanged for 17%, and cognition improved for 59% of 58 patients and remained stable for 40%. Effects on epilepsy were seen within days/weeks and were most pronounced in patients with early treatment initiation. Effects on movement disorders were noticed within months and were strongest in patients with higher cerebrospinal fluid-to-blood glucose ratio. Although side effects were minimal, 18% of 270 patients reported poor compliance. In individual patients, symptoms deteriorated upon low ketosis, poor compliance, or treatment discontinuation. Based on the good tolerability and strong favourable effect of dietary treatment on GLUT1DS symptoms, we advocate dietary treatment in all GLUT1DS patients and prompt diagnosis or screening to allow early treatment.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Disfunção Cognitiva/dietoterapia , Dieta Cetogênica , Epilepsia/dietoterapia , Proteínas de Transporte de Monossacarídeos/deficiência , Transtornos dos Movimentos/dietoterapia , Disfunção Cognitiva/etiologia , Epilepsia/etiologia , Humanos , Transtornos dos Movimentos/etiologiaRESUMO
OBJECTIVE: To assess risk factors for nasopharyngeal carriage of potential pathogens in geographically isolated Warao Amerindians in Venezuela. METHODS: In this point prevalence survey, nasopharyngeal swabs were obtained from 1064 Warao Amerindians: 504 children aged 0-4 years, 227 children aged 5-10 years and 333 caregivers. Written questionnaires were completed to obtain information on demographics and environmental risk factors. Anthropometric measurements were performed in children aged 0-4 years. RESULTS: Carriage rates of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis were 51%, 7%, 1% and 13%, respectively. Crowding index, method of cooking and tobacco exposure were not associated with increased carriage. In multivariable analysis, an increase in height-for-age Z score (i.e. improved chronic nutritional status) was associated with decreased odds of S. pneumoniae colonisation (OR 0.76, 95% CI 0.70-0.83) in children aged 0-4 years. CONCLUSIONS: Better knowledge of demographic and environmental risk factors facilitates better understanding of the dynamics of colonisation with respiratory bacteria in an Amerindian population. Poor chronic nutritional status was associated with increased pathogen carriage in children <5 years of age. The high rates of stunting generally observed in indigenous children may fuel the acquisition of respiratory bacteria that can lead to respiratory and invasive disease.
Assuntos
Portador Sadio , Bactérias Gram-Negativas/crescimento & desenvolvimento , Transtornos do Crescimento/complicações , Indígenas Sul-Americanos , Nasofaringe/microbiologia , Infecções Respiratórias/etiologia , Staphylococcus/crescimento & desenvolvimento , Adolescente , Adulto , Estatura , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prevalência , Infecções Respiratórias/microbiologia , Fatores de Risco , Inquéritos e Questionários , Venezuela , Adulto JovemRESUMO
The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.
Assuntos
Transmissão de Doença Infecciosa , Genótipo , Mycobacterium/classificação , Mycobacterium/isolamento & purificação , Tuberculose/epidemiologia , Tuberculose/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise por Conglomerados , Impressões Digitais de DNA , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Mycobacterium/genética , Países Baixos/epidemiologia , Filogenia , Medição de Risco , Tuberculose/microbiologia , Adulto JovemRESUMO
BACKGROUND: Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people. We determined the prevalence of Mycobacterium tuberculosis infection by TST and QuantiFERON®-TB Gold In-Tube (QFT-GIT) and assessed agreement between the two test methods and factors associated with positivity in either test in Warao Amerindian children in Venezuela. Furthermore, progression to active TB disease was evaluated for up to 12 months. METHODS: 163 HIV-negative childhood household contacts under 16 years of age were enrolled for TST, QFT-GIT and chest X-ray (CXR). Follow-up was performed at six and 12 months. Factors associated with TST and QFT-GIT positivity were studied using generalized estimation equations logistic regression models. RESULTS: At baseline, the proportion of TST positive children was similar to the proportion of children with a positive QFT-GIT (47% vs. 42%, p = 0.12). Overall concordance between QFT-GIT and TST was substantial (kappa 0.76, 95% CI 0.46-1.06). Previous BCG vaccination was not associated with significantly increased positivity in either test (OR 0.68, 95% CI 0.32-1.5 for TST and OR 0.51, 95% CI 0.14-1.9 for QFT-GIT). Eleven children were diagnosed with active TB at baseline. QFT-GIT had a higher sensitivity for active TB (88%, 95% CI 47-98%) than TST (55%, 95% CI 24-83%) while specificities were similar (respectively 58% and 55%). Five initially asymptomatic childhood contacts progressed to active TB disease during follow-up. CONCLUSION: Replacement of TST by the QFT-GIT for detection of M. tuberculosis infection is not recommended in this resource-constrained setting as test results showed substantial concordance and TST positivity was not affected by previous BCG vaccination. The QFT-GIT had a higher sensitivity than the TST for the detection of TB disease. However, the value of the QFT-GIT as an adjunct in diagnosing TB disease is limited by a high variability in QFT-GIT results over time.
Assuntos
Testes de Liberação de Interferon-gama/métodos , Teste Tuberculínico/métodos , Tuberculose Pulmonar/diagnóstico , Adolescente , Criança , Proteção da Criança , Pré-Escolar , Busca de Comunicante , Feminino , Humanos , Lactente , Masculino , Mycobacterium tuberculosis , Grupos Populacionais/estatística & dados numéricos , Valor Preditivo dos Testes , Kit de Reagentes para Diagnóstico , Tuberculose Pulmonar/epidemiologia , VenezuelaRESUMO
BACKGROUND: While in developed countries the prevalence of allergic diseases is rising, inflammatory diseases are relatively uncommon in rural developing areas. High prevalence rates of helminth and protozoan infections are commonly found in children living in rural settings and several studies suggest an inverse association between helminth infections and allergies. No studies investigating the relationship between parasitic infections and atopic diseases in rural children of developing countries under the age of 2 years have been published so far. We performed a cross-sectional survey to investigate the association of helminth and protozoan infections and malnutrition with recurrent wheezing and atopic eczema in Warao Amerindian children in Venezuela. METHODS: From August to November 2012, 229 children aged 0 to 2 years residing in the Orinoco Delta in Venezuela were enrolled. Data were collected through standardized questionnaires and physical examination, including inspection of the skin and anthropometric measurements. A stool sample was requested from all participants and detection of different parasites was performed using microscopy and real time polymerase chain reaction (PCR). RESULTS: We observed high prevalence rates of atopic eczema and recurrent wheezing, respectively 19% and 23%. The prevalence of helminth infections was 26% and the prevalence of protozoan infections was 59%. Atopic eczema and recurrent wheezing were more frequently observed in stunted compared with non-stunted children in multivariable analysis (OR 4.3, 95% CI 1.3 - 13.6, p = 0.015 and OR 4.5, 95% CI 0.97 - 21.2, p = 0.055). Furthermore, recurrent wheezing was significantly more often observed in children with protozoan infections than in children without protozoan infections (OR 6.7, 95% CI 1.5 - 30.5). CONCLUSIONS: High prevalence rates of atopic eczema and recurrent wheezing in Warao Amerindian children under 2 years of age were related to stunting and intestinal protozoan infections respectively. Helminth infections were not significantly associated with either atopic eczema or recurrent wheezing.
Assuntos
Dermatite Atópica/epidemiologia , Helmintíase/epidemiologia , Infecções por Protozoários/epidemiologia , Sons Respiratórios/etiologia , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Enteropatias/parasitologia , Masculino , Desnutrição/epidemiologia , Saúde da População Rural , População Rural , Inquéritos e Questionários , Venezuela/epidemiologia , Venezuela/etnologiaRESUMO
SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.
RESUMO
BACKGROUND: Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far. RESULTS: We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity). CONCLUSIONS: Our data justify the further exploration of our signature set as biomarkers for potential childhood TB diagnosis. We show that, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts.
Assuntos
Perfilação da Expressão Gênica , Indígenas Norte-Americanos/genética , Tuberculose/etnologia , Tuberculose/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genômica , Humanos , Lactente , Masculino , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The International Study on Asthma and Allergies in Childhood (ISAAC) reported a prevalence of asthma symptoms in 17 centers in nine Latin American countries that was similar to prevalence rates reported in non-tropical countries. It has been proposed that the continuous exposure to infectious diseases in rural populations residing in tropical areas leads to a relatively low prevalence of asthma symptoms. As almost a quarter of Latin American people live in rural tropical areas, the encountered high prevalence of asthma symptoms is remarkable. Wood smoke exposure and environmental tobacco smoke have been identified as possible risk factors for having asthma symptoms. METHODS: We performed a cross-sectional observational study from June 1, 2012 to September 30, 2012 in which we interviewed parents and guardians of Warao Amerindian children from Venezuela. Asthma symptoms were defined according to the ISAAC definition as self-reported wheezing in the last 12 months. The associations between wood smoke exposure and environmental tobacco smoke and the prevalence of asthma symptoms were calculated by means of univariate and multivariable logistic regression analyses. RESULTS: We included 630 children between two and ten years of age. Asthma symptoms were recorded in 164 of these children (26%). The prevalence of asthma symptoms was associated with the cooking method. Children exposed to the smoke produced by cooking on open wood fires were at higher risk of having asthma symptoms compared to children exposed to cooking with gas (AOR 2.12, 95% CI 1.18 - 3.84). Four percent of the children lived in a household where more than ten cigarettes were smoked per day and they had a higher risk of having asthma symptoms compared to children who were not exposed to cigarette smoke (AOR 2.69, 95% CI 1.11 - 6.48). CONCLUSION: Our findings suggest that children living in rural settings in a household where wood is used for cooking or where more than ten cigarettes are smoked daily have a higher risk of having asthma symptoms.
Assuntos
Asma/epidemiologia , Culinária , Indígenas Sul-Americanos/estatística & dados numéricos , Fumaça/efeitos adversos , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Medição de Risco , Poluição por Fumaça de Tabaco/efeitos adversos , Venezuela/epidemiologia , MadeiraRESUMO
BACKGROUND: Data from low- and middle-income countries (LMICs) show higher morbidity and mortality in children with acute respiratory illness (ARI) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, whether SARS-CoV-2 infection is distinct from other causes of ARI in this regard is unclear. We describe clinical characteristics and outcomes of South African children with SARS-CoV-2 and non-SARS-CoV-2 ARIs. METHODS: We performed a cross-sectional study including 0-13 years old children admitted to Tygerberg Hospital between May and December 2020 with an ARI. Routine clinical data were collected by the attending clinicians. All children underwent SARS-CoV-2 polymerase chain reaction testing. For severity of disease, the need for respiratory support and duration of support was considered. Multivariable logistic regression models were built to determine the factors associated with SARS-CoV-2 infection and severity. RESULTS: Data for 176 children were available, 38 (22%) children were SARS-CoV-2 polymerase chain reaction positive and 138 (78%) were negative. SARS-CoV-2 positive children were more likely to be female (OR: 2.68, 95% CI: 1.18-6.07), had lower weight-for-age Z score (OR: 0.76, 95% CI: 0.63-0.93), presented more frequently with fever (OR: 3.56, 95% CI: 1.54-8.24) and less often with cough (OR: 0.27, 95% CI: 0.11-0.66). SARS-CoV-2 infection was associated with significantly longer duration of oxygen treatment (median 8 vs. 3 days; OR: 1.1, 95% CI: 1.01-1.20). Overall, 66% of children had viral coinfection, with no significant difference between the groups. In total, 18% of SARS-CoV-2 positive children were readmitted within 3 months for a respiratory reason, compared with 15% SARS-CoV-2 negative children ( P = 0.64). CONCLUSIONS: Our data show that ARIs from SARS-CoV-2 cannot be easily differentiated, but were associated with a higher morbidity compared with ARIs from other causes. Overall outcomes were good. The long-term implications of severe SARS-CoV-2 pneumonia in young children in low- and middle-income countries require further study.
Assuntos
COVID-19 , Criança , Humanos , Feminino , Pré-Escolar , Recém-Nascido , Lactente , Adolescente , Masculino , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Estudos Transversais , África do Sul/epidemiologiaRESUMO
Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; P = 0.732). Only three participants required hospitalization for SARS-CoV-2. The proportions of participants with asymptomatic, mild, or moderate infections and the mean infection durations did not differ between randomization groups. In addition, unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes. The percentage of participants with seroconversion (7.8% versus 2.8%; P = 0.006) and mean SARS-CoV-2 anti-S1 antibody concentration (13.1 versus 4.3 IU/mL; P = 0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months postvaccination. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (ranging from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection. IMPORTANCE While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail. We found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity but may have enhanced SARS-CoV-2 antibody production during SARS-CoV-2 infection in the first 3 months after vaccination. These results are in agreement with other BCG trials that reported negative results (but did not use serological endpoints), except for two trials in Greece and India that reported positive results but had few endpoints and included endpoints that were not laboratory confirmed. The enhanced antibody production is in agreement with prior mechanistic studies but did not translate into protection from SARS-CoV-2 infection.