Effectiveness of COVID-19 Pfizer-BioNTech (BNT162b2) mRNA vaccination in adolescents aged 12-17 years: A systematic review and meta-analysis.

The rapid emergence of COVID-19 variants of concern (VOCs) has hindered vaccine uptake. To inform policy, we investigated the effectiveness of the BNT162b2 vaccination among adolescents against symptomatic and severe COVID-19 diseases using mostly real-world data (15 studies). We searched international databases until May 2022 and used Cochrane's risk of bias tools for critical appraisal. Random effects models were used to examine overall vaccine effectiveness (VE) across studies (general inverse-variance) and the effect of circulating VOCs on VE (log relative ratio and VE). Meta-regression assessed the effect of age and time on VE (restricted-maximum likelihood). BNT162b2 VE against PCR-confirmed SARS-CoV-2 was 82.7% (95%CI: 78.37-87.31%). VE was higher for severe (88%) than non-severe (35%) outcomes and declining over time improved following booster dose in omicron era [73%(95%CI:65-81%)]. Fully vaccinated adolescents are protected from COVID-19 circulating VOCs by BNT162b2 especially for the need of critical care or life support.

Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia: European Respiratory Society technical standard.

Nasal nitric oxide (nNO) is extremely low in most people with primary ciliary dyskinesia (PCD) and its measurement is an important contributor to making the diagnosis. Existing guidelines and technical standards focus on nNO measurements in older, cooperative children using chemiluminescence analysers. However, measurements of nNO in pre-school-age children (age 2-5 years) may facilitate early diagnosis and electrochemical rather than chemiluminescence analysers are widely used. Pre-schoolers often need different methods to be employed when measuring nNO. Hence, a European Respiratory Society Task Force has developed this technical standard as the first step towards standardising sampling, analysis and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups, including pre-school-age children. Furthermore, we considered both chemiluminescence and electrochemical analysers that are in use worldwide. There was a paucity of quality evidence for electrochemical analysers and sampling methods used in young children, and the Task Force proposes future research priorities to allow updates of this technical standard.

Bronchiectasis in African children: Challenges and barriers to care.

Bronchiectasis (BE) is a chronic condition affecting the bronchial tree. It is characterized by the dilatation of large and medium-sized airways, secondary to damage of the underlying bronchial wall structural elements and accompanied by the clinical picture of recurrent or persistent cough. Despite an increased awareness of childhood BE, there is still a paucity of data on the epidemiology, pathophysiological phenotypes, diagnosis, management, and outcomes in Africa where the prevalence is mostly unmeasured, and likely to be higher than high-income countries. Diagnostic pathways and management principles have largely been extrapolated from approaches in adults and children in high-income countries or from data in children with cystic fibrosis. Here we provide an overview of pediatric BE in Africa, highlighting risk factors, diagnostic and management challenges, need for a global approach to addressing key research gaps, and recommendations for practitioners working in Africa.

An international survey on nasal nitric oxide measurement practices for the diagnosis of primary ciliary dyskinesia.

Nasal nitric oxide (nNO) measurements are used in the assessment of patients suspected of having primary ciliary dyskinesia (PCD), but recommendations for performing such measurements have not focused on children and do not include all current practices. To guide the development of a European Respiratory Society-supported technical standard for nNO measurement in children, an international online survey was conducted to better understand current measurement practices among providers involved in PCD diagnostics. 78 professionals responded, representing 65 centres across 18 countries, mainly in Europe and North America. Nearly all centres measured nNO in children and more than half performed measurements before 5 years of age. The test was often postponed in children with signs of acute airway infection. In Europe, the electrochemical technique was more frequently used than chemiluminescence. A similar proportion of centres performed measurements during exhalation against a resistance (49 out of 65) or during tidal breathing (50 out of 65); 15 centres used only exhalation against a resistance and 15 used only tidal breathing. The cut-off values used to discriminate PCD were consistent across centres using chemiluminescence analysers; these centres reported results as an output (nL·min-1). Cut-off values were highly variable across centres using electrochemical devices, and nNO concentrations were typically reported as ppb. This survey is the first to determine real-world use of nNO measurements globally and revealed remarkable variability in methodology, equipment and interpretation. These findings will help standardise methods and training.

Diagnosing Pulmonary Tuberculosis by Using Sequence-Specific Purification of Urine Cell-Free DNA.

Transrenal urine cell-free DNA (cfDNA) is a promising tuberculosis (TB) biomarker, but is challenging to detect because of the short length (<100 bp) and low concentration of TB-specific fragments. We aimed to improve the diagnostic sensitivity of TB urine cfDNA by increasing recovery of short fragments during sample preparation. We developed a highly sensitive sequence-specific purification method that uses hybridization probes immobilized on magnetic beads to capture short TB cfDNA (50 bp) with 91.8% average efficiency. Combined with short-target PCR, the assay limit of detection was ≤5 copies of cfDNA in 10 ml urine. In a clinical cohort study in South Africa, our urine cfDNA assay had 83.7% sensitivity (95% CI: 71.0 to 91.5%) and 100% specificity (95% CI: 86.2 to 100%) for diagnosis of active pulmonary TB when using sputum Xpert MTB/RIF as the reference standard. The detected cfDNA concentration was 0.14 to 2,804 copies/ml (median 14.6 copies/ml) and was inversely correlated with CD4 count and days to culture positivity. Sensitivity was nonsignificantly higher in HIV-positive (88.2%) compared to HIV-negative patients (73.3%), and was not dependent on CD4 count. Sensitivity remained high in sputum smear-negative (76.0%) and urine lipoarabinomannan (LAM)-negative (76.5%) patients. With improved sample preparation, urine cfDNA is a viable biomarker for TB diagnosis. Our assay has the highest reported accuracy of any TB urine cfDNA test to date and has the potential to enable rapid non-sputum-based TB diagnosis across key underserved patient populations.

Obstructive Sleep Apnea Awareness among Primary Care Physicians in Africa.

Rationale: Obstructive sleep apnea (OSA) is a significant health problem among adults and children globally, resulting in decreased quality of life and increased costs of healthcare. For optimal clinical care, primary care physicians should be familiar with OSA and confident in their ability to screen, diagnose, and manage this condition.Objectives: To assess the knowledge, attitudes, and practices of primary care physicians in Kenya, Nigeria, and South Africa regarding OSA in adults and children.Methods: We conducted a multicenter cross-sectional survey in Kenya (Nairobi), Nigeria (Edo State), and South Africa (Cape Town) between April 2016 and July 2017. At least 40 participants were randomly selected from a register of primary care physicians at each site. Potential participants were contacted to receive online/paper-based, validated OSA Knowledge and Attitudes (OSAKA) and OSAKA in Children (OSAKA-KIDS) questionnaires related to adults and children, respectively. The median percentage knowledge scores and proportions of favorable attitude were computed and current diagnostic and referral practices were documented.Results: The median OSAKA knowledge scores were 83.3% (interquartile range [IQR], 77.8-88.9), 66.7% (IQR, 55.6-77.8), and 61.1% (IQR, 55.6-77.8) among South African, Kenyan, and Nigerian physicians, respectively. For OSAKA-KIDS, the median knowledge scores were 61.1% (IQR, 50.0-72.2), 64.2% (IQR, 35.3-93.2), and 58.3% (IQR, 44.4-66.7) among South African, Kenyan, and Nigerian physicians, respectively. Most physicians (90-94%) considered adult and pediatric OSA very/extremely important. Fewer physicians agreed/strongly agreed that they were confident about OSA diagnosis (55%), management (25%), and continuous positive airway pressure (18%) use in adults. Even fewer physicians agreed/strongly agreed that they were confident about pediatric OSA diagnosis (35%), management (21%), and continuous positive airway pressure use (18%). South African physicians mainly prescribed polysomnography (51%) and overnight oximetry (22%), whereas 49% of Nigerian physicians and 65% of Kenyan physicians commonly requested lateral cervical radiography.Conclusions: Primary care physicians in South Africa, Nigeria, and Kenya considered OSA to be important but had modest knowledge about OSA in adults and children, and had a low perceived confidence in adult and pediatric management. Focused educational interventions during undergraduate training and continuing professional development programs may improve primary physicians' knowledge about OSA and its diagnosis and management.

Exogenous lipoid pneumonia in children: A systematic review.

OBJECTIVES: To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP). DESIGN: Systematic review. We searched electronic databases and reference lists published between 1967 and 2018, restricted to non-accidental cases. RESULTS: Forty-four studies including 489 participants aged 1 day to 17 years from 13 countries were included. Cultural, medical, and behavioural rationale for oil-use was described. The clinical-radiological presentation varied widely. Diagnostic certainty was deemed highest if ELP was confirmed on bronchoalveolar lavage/frozen section lung biopsy with documented extracellular lipid on cytological staining and/or fat analysis. Non-tuberculous mycobacteria infection was identified in six studies: Mycobacterium fortuitum/chelonei, Mycobacterium smegmatis and Mycobacterium abscessus. Treatment comprised supportive therapy, corticosteroids, stopping oil, therapeutic lung-lavage and surgical resection. Outcomes were reported inconsistently. CONCLUSION: Paediatric ELP resulting from cultural and medical practices continues to be described globally. Preventive interventions, standardized reporting, and treatment efficacy studies for cases not averted, are lacking. Protocol registration: PROSPERO CRD42017068313.

Childhood pneumonia in low-and-middle-income countries: An update.

OBJECTIVES: To review epidemiology, aetiology and management of childhood pneumonia in low-and-middle-income countries. DESIGN: Review of published English literature between 2013 and 2019. RESULTS: Pneumonia remains a major cause of morbidity and mortality. Risk factors include young age, malnutrition, immunosuppression, tobacco smoke or air pollution exposure. Better methods for specimen collection and molecular diagnostics have improved microbiological diagnosis, indicating that pneumonia results from several organisms interacting. Induced sputum increases microbiologic yield for Bordetella pertussis or Mycobacterium tuberculosis, which has been associated with pneumonia in high TB prevalence areas. The proportion of cases due to Streptococcus pneumoniae and Haemophilus influenzae b has declined with new conjugate vaccines; Staphylococcus aureus and H. influenzae non-type b are the commonest bacterial pathogens; viruses are the most common pathogens. Effective interventions comprise antibiotics, oxygen and non-invasive ventilation. New vaccines have reduced severity and incidence of disease, but disparities exist in uptake. CONCLUSION: Morbidity and mortality from childhood pneumonia has decreased but a considerable preventable burden remains. Widespread implementation of available, effective interventions and development of novel strategies are needed.

Implementation of Isoniazid Preventive Therapy Among HIV-Infected Children at Health Facilities in Nairobi County, Kenya: A Cross-Sectional Study.

BACKGROUND: HIV is the strongest risk factor for developing tuberculosis (TB) among people with latent or new Mycobacterium tuberculosis infection. Isoniazid preventive therapy (IPT) reduces the risk of active TB among people living with HIV by up to 62%. Despite evidence that IPT is safe and efficacious, its provision remains low globally. The current study aimed at documenting IPT uptake, adherence, and completion rates, as well as the correlates of IPT uptake among HIV-infected children in Kenya. The study also assessed the knowledge, attitude, and practices of health-care workers (HCWs) with regard to IPT. METHODS: A health facility-based cross-sectional study was conducted. Data were collected from caregivers of HIV-infected children as well as HCWs using an interviewer-administered questionnaire. Logistic regression was used to determine the factors associated with IPT uptake. RESULTS: The study enrolled 111 child-caregiver dyads. Most of the caregivers were female (n=75, 77.3%) and HIV-positive (n=82, 85.4%). The majority of children were male (n=65, 58.6%) and on ART (n=106, 95.5%). Overall, 59 children were on IPT (uptake of 53.2%, 95% confidence interval [CI], 43.9% to 62.4%). Out of the 25 children who had been on IPT for more than 6 months, 22 (88.0%) successfully completed the 6-month course of treatment. Further, 27 of the 34 children (78.4%) who were on IPT at the time of the study demonstrated satisfactory adherence to the therapy (no doses missed). The caregivers' attributes that were associated with IPT uptake included having a secondary school education (adjusted odds ratio [aOR] 0.13; 95% CI, 0.03 to 0.67) and having been on IPT (aOR 27.50; 95% CI, 5.39 to 140.28). The characteristics of children that were significantly associated with IPT uptake were higher median baseline CD4 count (P=.007) and higher median current CD4 count (P=.024). CONCLUSION: The study demonstrated suboptimal IPT uptake but favourable adherence and treatment completion rates. There was almost universal awareness of IPT within the study sample. Furthermore, the majority of the HCWs had a favourable attitude towards IPT. However, the attendant IPT practices were inadequate, with majority of HCWs reporting that they had never initiated IPT, prescribed IPT within the last 12 months, or renewed an isoniazid prescription.

Exogenous lipoid pneumonia: an important cause of interstitial lung disease in infants.

Exogenous lipoid pneumonia (ELP), an important cause of interstitial lung disease, often goes unrecognized. We conducted a retrospective study of children with histologically confirmed ELP at Red Cross Children's Hospital, South Africa. Twelve children of Zimbabwean heritage aged 2.1-10.8 months were identified between 2012 and 2017. Repeated oral administration of plant-based oil for cultural reasons was reported by 10 of 11 caregivers. Cough (12/12), tachypnoea (11/12), hypoxia (9/12), and diffuse alveolar infiltrates on chest radiography (12/12) were common at presentation. Chest computed tomography revealed ground-glass opacification with lower zone predominance (9/9) and interlobular septal thickening (8/9). Bronchoalveolar lavage specimens appeared cloudy/milky, with abundant lipid-laden macrophages and extracellular lipid on Oil-Red-O staining (12/12), with polymicrobial (6/12) and Mycobacterium abscessus (2/12) co-infection. Antibiotics, systemic corticosteroids, and therapeutic lavage were interventions in all eight and five patients, respectively. Clinicians should consider ELP in children with non-resolving pneumonia in settings with similar practices.

Summer schools of adult and paediatric respiratory medicine: course report.

Participants in the 2017 ERS summer schools of adult and paediatric respiratory medicine describe their experiences http://ow.ly/i4y930hzLU0.

Stakeholder perspectives for optimization of tuberculosis contact investigation in a high-burden setting.

INTRODUCTION: Optimal tuberculosis contact investigation impacts TB prevention, timely case finding and linkage to care, however data on routine implementation in high burden contexts is limited. MATERIALS AND METHODS: In a multi-method qualitative study based on individual interviews with TB patients, facility observations and focus group discussions with health workers (HWs) in 13 public health facilities, and key informant interviews with governmental and non-governmental experts, we describe TB contact investigation in the context of an urban setting in Kenya and identify opportunities for optimization. RESULTS: Invitation of TB patients to bring close contacts by HWs was key for all patient decisions that led to contact screening in addition to patients' understanding of TB transmission and desire to avoid contacts suffering from TB. Sub-optimal HW enquiry of TB patients and contacts presenting at the facility were missed opportunities which stemmed from lack of standardized operational procedures, documentation tools and HW training. Stakeholders proposed provision of fast tracked and holistic health packages for contacts seeking TB screening, and sustainable government led funding for the requisite infrastructure and workforce. CONCLUSION: TB contact invitation by HWs leading to contact screening occurs in this context. Stakeholder perspectives inform the design of an operational framework for optimized delivery.

ADAPTING A STIGMA SCALE FOR ASSESSMENT OF TUBERCULOSIS-RELATED STIGMA AMONG ENGLISH/SWAHILI-SPEAKING PATIENTS IN AN AFRICAN SETTING.

OBJECTIVE: To adapt a validated instrument that quantitatively measures stigma among English/Swahili speaking TB (tuberculosis) patients in Kenya, a high burden TB country. METHODS: Following ethical approval, we elicited feedback on the English and Swahili translated Stigma Scale for Chronic Illness (SSCI) tools through cognitive interviews. We assessed difficulties in translation, differences in meaning, TB contextual relevance, patients' acceptability to the questions, and issues in tool structure. The interviews were audio recorded, transcribed and translated. Open coding and thematic analysis of the data was conducted by two independent researchers. RESULTS: Between May and September 2015 we conducted a qualitative study among 20 adult TB patients attending 11 health facilities in Nairobi County, Kenya. Most questions were understood in both English and Swahili, deemed relevant in the context of TB and acceptable to TB patients. Key areas of adaptation of the SSCI included adding questions addressing fear of infecting others and death, HIV stigma, and intimate, family and workplace relationship contexts. Questions were revised for non-redundancy, specificity and optimized sequence. CONCLUSION: The adapted 8-item SSCI appears to be a useful tool that may be administered by health workers in English or Swahili to quantify TB stigma among TB patients in Kenya.

Perspectives of host faculty and trainees on international visiting faculty to paediatric academic departments in East Africa.

BACKGROUND: Investments in faculty exchanges to build physician workforce capacity are increasing. Little attention has been paid to the expectations of host institution faculty and trainees. This prospective qualitative research study explored faculty and resident perspectives about guest faculty in paediatric departments in East Africa, asking (1) What are the benefits and challenges of hosting guest faculty, (2) What factors influence the effectiveness of faculty visits and (3) How do host institutions prepare for faculty visits? METHODS: We recruited 36 faculty members and residents from among four paediatric departments in East Africa to participate in semistructured interviews which were audio recorded and transcribed. Data were qualitatively analysed using principles of open coding and thematic analysis. We achieved saturation of themes. RESULTS: Benefits of faculty visits varied based on the size and needs of host institutions. Emergent themes included the importance of guest faculty time commitment, and mutual preparation to ensure that visit goals and scheduling met host needs. We documented conflicts that developed around guest emotional responses and ethical approaches to clinical resource limitations, which some hosts tried to prepare for and mitigate. Imbalance in resources led to power differentials; some hosts sought partnerships to re-establish control over the process of having guests. CONCLUSIONS: We identified that guest faculty can assist paediatric institutions in building capacity; however, effective visits require: (1) mutually agreed on goals with appropriate scheduling, visit length and commitment to ensure that the visits meet the host's needs, (2) careful selection and preparation of guest faculty to meet the host's goals, (3) emotional preparation by prospective guests along with host orientation to clinical work in the host's setting and (4) attention to funding sources for the visit and mitigation of resulting power differentials.

Wheeze as an adverse event in pediatric vaccine and drug randomized controlled trials: A systematic review.

INTRODUCTION: Wheeze is an important sign indicating a potentially severe adverse event in vaccine and drug trials, particularly in children. However, there are currently no consensus definitions of wheeze or associated respiratory compromise in randomized controlled trials (RCTs). OBJECTIVE: To identify definitions and severity grading scales of wheeze as an adverse event in vaccine and drug RCTs enrolling children <5 years and to determine their diagnostic performance based on sensitivity, specificity and inter-observer agreement. METHODS: We performed a systematic review of electronic databases and reference lists with restrictions for trial settings, English language and publication date ≥1970. Wheeze definitions and severity grading were abstracted and ranked by a diagnostic certainty score based on sensitivity, specificity and inter-observer agreement. RESULTS: Of 1205 articles identified using our broad search terms, we identified 58 eligible trials conducted in 38 countries, mainly in high-income settings. Vaccines made up the majority (90%) of interventions, particularly influenza vaccines (65%). Only 15 trials provided explicit definitions of wheeze. Of 24 studies that described severity, 11 described wheeze severity in the context of an explicit wheeze definition. The remaining 13 studies described wheeze severity where wheeze was defined as part of a respiratory illness or a wheeze equivalent. Wheeze descriptions were elicited from caregiver reports (14%), physical examination by a health worker (45%) or a combination (41%). There were 21/58 studies in which wheeze definitions included combined caregiver report and healthcare worker assessment. The use of these two methods appeared to have the highest combined sensitivity and specificity. CONCLUSION: Standardized wheeze definitions and severity grading scales for use in pediatric vaccine or drug trials are lacking. Standardized definitions of wheeze are needed for assessment of possible adverse events as new vaccines and drugs are evaluated.

Prevalence and associated factors of pulmonary hypertension in Kenyan children with adenoid or adenotonsillar hypertrophy.

OBJECTIVES: Adenotonsillar hypertrophy is a common condition in childhood, whose serious complications of pulmonary hypertension and cor pulmonale are devastating but local prevalence is unknown. This study determined the prevalence and associated factors of pulmonary hypertension in children with adenoid or adenotonsillar hypertrophy at Kenyatta National Hospital, Kenya. METHODS: This was a cross sectional hospital based survey conducted among children below 12 years of age with clinical and radiological adenoid hypertrophy attending the ear, nose and throat (ENT) outpatient clinic and general pediatric wards. Doppler echocardiography was used to determine pulmonary hypertension defined as a mean pulmonary arterial pressure (mPAP) of ≥ 25 mm Hg using the Chemla equation. Children with mPAP of ≥ 25 mm Hg were compared to those with lower pressures and clinical and radiological factors associated with pulmonary hypertension determined using multivariate logistic regression analysis. RESULTS: Of the 123 eligible children in the study, 27 had pulmonary hypertension giving a prevalence of 21.9% (95% CI 14.64%-29.27%). Independent factors associated with pulmonary hypertension included nasal obstruction (OR=3.0 [95% CI 1.08-8.44] p=0.035) and hyperactivity on history (OR=0.2 [95% CI 0.07-0.59] p=0.003) and adenoid-nasopharyngeal ratio (ANR) >0.825 on lateral neck radiography (OR=5.0 [95% CI 1.01-24.37] p=0.048). CONCLUSION: One in five children with adenoid or adenotonsillar hypertrophy had pulmonary hypertension with a 3-fold and 5-fold increased odds in those with nasal obstruction on history and ANR >0.825 on lateral neck radiography respectively and an 80% reduced odds in reportedly hyperactive children.