Transmission and progression to disease of Mycobacterium tuberculosis phylogenetic lineages in The Netherlands

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.This study was supported by the Portuguese Foundation for Science and Technology (FCT) (reference SFRH/BD/33902/2009 to H.N.-G

COVID-19 response in low- and middle-income countries : don’t overlook the role of mobile phone communication

CITATION: Verhagen, L. M. et al. 2020. COVID-19 response in low- and middle-income countries: Don’t overlook the role of mobile phone communication. International Journal of Infectious Diseases, 99: 334-337. doi:10.1016/j.ijid.2020.07.069.The original publication is available at https://www.journals.elsevier.com/international-journal-of-infectious-diseasesEstimates of health capacities in the context of the coronavirus disease 2019 (COVID-19) pandemic indicate that most low- and middle-income countries (LMICs) are not operationally ready to manage this health emergency. Motivated by worldwide successes in other infectious disease epidemics and our experience in Sub-Saharan Africa, we support mobile phone communication to improve data collection and reporting, communication between healthcare workers, public health institutions, and patients, and the implementation of disease tracking and subsequent risk-stratified isolation measures. Programmatic action is needed for centrally coordinated reporting and communication systems facilitating mobile phones in crisis management plans for addressing the COVID-19 pandemic in LMICs. We summarize examples of worldwide mobile phone technology initiatives that have enhanced patient care and public health outcomes in previous epidemics and the current COVID-19 pandemic. In addition, we provide an overview of baseline conditions, including transparency about privacy guarantees, necessary for the successful use of mobile phones in assisting in the fight against COVID-19 spread.https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1201971220306251?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1201971220306251%3Fshowall%3Dtrue&referrer

Nasopharyngeal Microbiota Profiles in Rural Venezuelan Children Are Associated With Respiratory and Gastrointestinal Infections

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

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data

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

Clinical experience with severe acute respiratory syndrome Coronavirus 2-related illness in children : hospital experience in Cape Town, South Africa

CITATION: van der Zalm, M. M. et al. 2021. Clinical Experience With Severe Acute Respiratory Syndrome Coronavirus 2-Related Illness in Children: Hospital Experience in Cape Town, South Africa. Clinical infectious diseases, 72(12):e938–e944. doi:10.1093/cid/ciaa1666The original publication is available at https://academic.oup.com/cid/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 (n = 62), with a median age of 13.5 months (IQR, 1.8-43.5 months) were younger than children not admitted (n = 97; median age, 81.0 months [IQR, 34.5-120.5 months]; P < .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.https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac266/6591403Publishers versio

Mycoplasma pneumoniae carriage in children with recurrent respiratory tract infections is associated with a less diverse and altered microbiota

BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors. METHODS: We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing. FINDINGS: Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06-0.37]) and total IgG deficiency (OR 0.15 [0.02-0.74]) were less prevalent in M.pneumoniae carriers (n = 78) compared to non-carriers (n = 36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09-0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74-1608.11]) compared to non-carriers. INTERPRETATION: M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H. influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H. influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members. FUNDING: Wilhelmina Children's Hospital Research Fund, 'Christine Bader Stichting Irene KinderZiekenhuis', Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen)

Recurrent, protracted and persistent lower respiratory tract infection : A neglected clinical entity

Community-acquired pneumonia is a potentially life-threatening disease affecting children worldwide. Recurrent pneumonia episodes can lead to the development of chronic respiratory morbidity. Chronic wet cough, a common pediatric complaint, is defined as a wet cough indicating excessive airway mucus that lasts for a minimum of 4 weeks. Most children with a chronic wet cough do not suffer from underlying debilitating pulmonary disorders. Rather, chronic wet cough is generally associated with neutrophilic airway inflammation and bacterial infections of the conducting airways. Failure to characterize endobronchial infections has led to under-recognition of chronic wet cough as an important clinical entity in children. Under-recognition and under-treatment of protracted bacterial bronchitis (PBB), a diagnosis made by the presence of isolated cough >4 weeks that resolves with appropriate antibiotic treatment, may lead to the development of chronic suppurative lung disease (CSLD) and bronchiectasis. The burden of bronchiectasis is highest in developing countries and in specifically vulnerable populations in developed countries, in particular indigenous children living in remote communities. The incidence, hospitalization rates and risk of long term sequelae of childhood pneumonia in indigenous children are higher than in non-indigenous children residing in the same area. The overlapping clinical and pathophysiological characteristics of PBB, CSLD and bronchiectasis are the presence of a chronic wet cough, impaired mucociliary clearance of the conducting airways, the presence of endobronchial bacterial infection (mainly non-typeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis) and neutrophilic airway inflammation. The principles of managing PBB, CSLD and bronchiectasis are the same. More research and public health interventions are required to improve the awareness, diagnosis and management of these causes of chronic wet cough in children

Glucose transporter type 1 deficiency syndrome and the ketogenic diet

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

Bacterial Respiratory Pathogens in Children With Inherited Immune and Airway Disorders: Nasopharyngeal Carriage and Disease Risk

Children with primary immunodeficiencies, sickle cell disease and cystic fibrosis are at risk to develop invasive bacterial infections caused by respiratory tract pathogens, in particular Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. This review article evaluates the role of nasopharyngeal colonization by these pathogens in the high prevalence of respiratory and invasive infections in children with inherited disorders affecting the immune system or the respiratory tract. We conclude that respiratory and invasive diseases that occur in children with primary immunodeficiencies or sickle cell disease are probably a result of increased nasopharyngeal colonization rates compared with healthy children. However, when the inherited disorder is characterized by local airway abnormalities such as in cystic fibrosis, enhanced nasopharyngeal colonization does not seem to play a major role in invasive disease risk. As the evidence for the role of nasopharyngeal colonization in disease risk in these specific patient groups partly comes from experimental studies and animal models, longitudinal studies in children are needed. Detailed understanding of the effect of colonization on the development of respiratory and invasive infections in children with primary immunodeficiencies, sickle cell disease or cystic fibrosis provides a justification for the selective introduction of vaccination and prophylactic antibiotic treatment. Recommendations for the use of (preventive) therapeutic strategies in these patient groups taking into account disease-specific immunologic mechanisms underlying colonization and disease are described

The microbiota in respiratory tract infections: from association to intervention.

Purpose of reviewThe 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 findingsRecent 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.SummaryImproved 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