Functional Outcomes of Congenital Scoliosis at a Mean 35-Year Follow-up Post In Situ Fusion. Revisiting Patients From the 2002 Goldberg et al Study.

BACKGROUND: The management of congenital scoliosis poses a significant challenge for treating surgeons. The aim of our study was to provide insight into the long-term clinical results of spinal fusion in congenital scoliosis. METHODS: We performed a retrospective review of the scoliosis database in our institution for the period 1976 until 2002 identifying 43 patients with congenital scoliosis who underwent spinal fusion. Patient demographics, diagnosis, levels fused, and radiographs were evaluated. Patients were evaluated for unplanned return to the operating room (UPROR) via SRS 22, EQ5D-5L, and Oswestry Disability Index (ODI). RESULTS: Of the 43 patients who fulfilled the inclusion criteria, 22 patients agreed to participate, 3 patients were known to be deceased and 18 patients were lost to follow-up or declined to participate and were excluded. The mean age of the respondents was 40.7 years (range, 30 to 47 y) with a mean follow-up from index surgery of 35 years (range, 20 to 44 y). At most recent follow-up, 12 patients (54%) underwent UPROR. The mean age at diagnosis was 3.4 years (range, birth to 11.5 y), and the mean age for first surgery was 5.8 years (range, 1 to 13 y). As regards radiologic follow-up; the mean number of levels fused was 5.2 (range, 2 to 12). Thoracic fusion was performed in 17 patients (77%). The mean T1 to T12 height at index surgery and maturity was 166 mm (range, 130 to 240 mm) and 202 mm (range, 125 to 270 mm), respectively. The mean functional scores at follow-up were SRS 22: 4.5 (range, 2.4 to 5), cumulative EQ5D-5L score 7.2 (range, 5 to 15), and ODI: 8% (range, 2 to 30%). All respondents completed high school, 10 patients (45%) completed university, and 2 patients were awarded doctorates. Currently, 17 patients (77%) are in paid employment. CONCLUSIONS: This report constitutes the largest series of patients treated by spinal arthrodesis for congenital scoliosis followed into maturity. We demonstrate the thorax continues to grow after index fusion, patient-reported outcomes were satisfactory with superior educational and employment rates and unplanned return to theatre is rare in adult life. LEVEL OF EVIDENCE: Therapeutic Level IV.

Factors predicting mortality in hospitalised HIV-negative children with lower-chest-wall indrawing pneumonia and implications for management.

INTRODUCTION: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. METHODS: PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. RESULTS: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). CONCLUSIONS: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community.

Antibiotic and antifungal use in paediatric departments at three academic hospitals in South Africa.

Objectives: South Africa implemented a National Strategic Framework to optimise antimicrobial stewardship in 2014; however, there is limited data on how this has affected prescribing, especially to children treated in academic centres. Methods: We conducted a point prevalence survey using the World Health Organization (WHO) methodology to evaluate antibiotic and antifungal prescribing practices in paediatric departments at three academic hospitals in South Africa. Results: We recorded 1946 antimicrobial prescriptions in 1191 children, with 55.2% and 39.2% of the antibiotics classified as WHO AWaRe Access and Watch drugs, respectively. There were significant differences in prescription of Reserve antibiotics and antifungals between institutions. Receipt of WHO Watch and Reserve antibiotics was independently associated with infancy (<12 months) and adolescents (13-17 years) (adjusted relative risk [aRR]: 2.09-9.95); prolonged hospitalisation (aRR: 3.29-30.08); rapidly or ultimately fatal illness (aRR: 1.94 to 5.52); and blood transfusion (aRR: 3.28-5.70). Antifungal prescribing was associated with treatment of hospital-associated infection (aRR: 2.90), medical prophylaxis (aRR: 3.30), and treatment in intensive care units (aRR: 2.15-2.27). Conclusions: Guidance on optimisation of infection prevention and control practice and strengthening of antimicrobial stewardship would impact positively on the care of sick children in our setting.

Post-transplant lymphoproliferative disorder in pediatric liver transplant recipients: Experience from a South African transplant center.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a clinically heterogeneous potentially fatal complication of pediatric liver transplantation (PLT). We determined the prevalence, complications, and associated factors for PTLD in PLT recipients from Wits Donald Gordon Medical Centre, South Africa from January 2012 to August 2019. METHODS: We performed a retrospective record review of 150 PLT recipients. RESULTS: Histologically proven PTLD occurred in 17/150 PLT recipients (11.3%). Children with PTLD were significantly younger at transplant (17.9 vs. 32.7 months, p = 0.001) with a significantly higher prevalence of obstructive etiology (17/17 vs. 81/133, p = 0.001). Fifteen (88.2%) children with PTLD were Epstein-Barr virus (EBV) seronegative at transplant. High post-transplant EBV viral load at a threshold value of 4.8 log10 DNA copies/mL (sensitivity: 80.0% [95% confidence interval {CI}, 46.7%-100.0%]; specificity: 73.1% [95% CI 42.3%-93.3%; area under the curve {AUC} 75.8%]) and low post-transplant albumin levels at a threshold value of 21.5 g/L (sensitivity: 70.6% [95% CI, 41.2%-94.1%]; specificity: 85.7% [95% CI, 60.4%-94.5%; {AUC} 74.8%]) were associated with PTLD. The prevalence of cytomegalovirus (CMV) disease was significantly higher in children who developed PTLD versus non-PTLD (12/17 vs. 18/133; p < 0.001). CMV disease and the combination of post-transplant high EBV viral load and low albumin were independently associated with an increased risk of developing PTLD. Four (23.5%) children with PTLD died, however, survival was equivalent to non-PTLD PLT (p = 0.580). CONCLUSION: The prevalence of PTLD in our cohort mirrors international cohorts, with mortality similar to non-PTLD PLT recipients.

Healthcare-associated Infections Drive Antimicrobial Prescribing in Pediatric Departments at Three Academic Hospitals in South Africa.

BACKGROUND: The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals. METHODS: This cross-sectional study included hospitalized neonates and children (0-15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site. RESULTS: Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5-32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6-12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06-2.53], infants (aRR: 1.57; 95% CI: 1.12-2.21) and adolescents (aRR: 2.18; 95% CI: 1.45-3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04-1.70) and underweight (aRR: 1.25; 95% CI: 1.01-1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI. CONCLUSIONS: The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level.

All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020-22) compared with the pre-pandemic period (2015-19) in South Africa: an observational study.

BACKGROUND: Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period. METHODS: In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015-19). FINDINGS: Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67-0·74) and 13% lower in 2021 (0·87, 0·83-0·91), but 16% higher in 2022 (1·16, 1·11-1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45-0·58), influenza-associated LRTI (0·05, 0·02-0·11), and pulmonary tuberculosis (0·52, 0·41-0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95-1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92-1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65-0·94) and IPD (0·51, 0·24-0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19-0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97-1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03-1·58). INTERPRETATION: The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted. FUNDING: The Bill & Melinda Gates Foundation.

Age as a predictor of additional surgeries following initial closed reduction for children with developmental dysplasia of the hip: the 10-year experience of a national paediatric orthopaedic unit.

BACKGROUND AND PURPOSE: Dislocated and unstable hip joints which do not stabilize in an orthosis in the neonatal period require operative intervention to achieve a stable concentric joint. The aim of this study is to assess the requirement for further operative intervention in patients who have undergone successful closed reduction to treat developmental dysplasia of the hip (DDH). METHODS: We identified all patients who had undergone closed reduction of an unstable hip joint at our institution within 10 years, with further identification of patients who underwent a second procedure. We used logistic regression to evaluate correlation between age at closed reduction and the probability of secondary procedures. RESULTS: A total of 694 patients (84.5% females) who underwent a closed reduction in the study period were identified. 235 were excluded (patients with underlying genetic conditions, neuromuscular disorders, syndromic disorders). 250 patients had closed reductions only. 209 patients (45.5%) had at least 1 secondary procedure after their initial closed reduction. In multivariable analysis, female gender (OR 0.310; 95% CI, 0.108-0.885; p = 0.029) and patients aged ⩽12 months at the time of first surgery (OR 0.055; 95% CI, 0.007-0.423; p = 0.005) independently predicted being less likely to require a second surgery for their DDH. DISCUSSION: In conclusion, we found that a significant proportion of children (45.5%) who underwent closed reduction of a dislocated hip required additional surgical intervention in early childhood. Our data show that those children who undergo later closed reduction of a dislocated hip in DDH after 12 months of age, and male infants, have a significantly higher incidence of additional surgical intervention.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Healthcare disparity and its associations with cytomegalovirus disease in pediatric liver transplant recipients in South Africa.

BACKGROUND: Cytomegalovirus (CMV) infection and disease are preventable complications following pediatric liver transplantation (PLT), despite the use of prophylaxis to minimize the risk of CMV disease. We evaluated the incidence and complications of CMV disease in PLT recipients in South Africa (SA), with particular reference to potential differences in outcome between state and private sector patients. METHODS: Medical records of patients younger than 16 years of age who received liver transplants between January 1, 2012, and August 31, 2018 were analyzed. RESULTS: Records of all 150 PLT patients were retrieved. The median age at transplant was 29.2 months (95% confidence interval 15.6-58.4) and follow-up was 46.3 months (interquartile range 27.6-63.1). Sixty-six (44%) patients were high risk, 79 (52.7%) were intermediate risk, and five (3.3%) were low risk for CMV infection. Forty-three (28.9%) patients had CMV DNAemia following transplantation, and 30 (20.1%) developed CMV disease. Receipt of care in the private sector was consistently associated with a lower hazard of CMV disease (adjusted hazard ratio [aHR] ranging from 0.36 to 0.43) and a consistently lower hazard of death among recipients at high risk for CMV disease and/or those who developed CMV disease (aHR ranging from 0.28 to 0.33). CONCLUSION: Receipt of care in the private health sector was associated with a consistently lower hazard of CMV disease and death in individuals with CMV disease and/or at high risk for CMV disease. Policies aimed at creating a more equitable healthcare system in SA may mitigate the differential burden of illness associated with CMV in PLT recipients.

Digitally recorded and remotely classified lung auscultation compared with conventional stethoscope classifications among children aged 1-59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) case-control study.

BACKGROUND: Diagnosis of pneumonia remains challenging. Digitally recorded and remote human classified lung sounds may offer benefits beyond conventional auscultation, but it is unclear whether classifications differ between the two approaches. We evaluated concordance between digital and conventional auscultation. METHODS: We collected digitally recorded lung sounds, conventional auscultation classifications and clinical measures and samples from children with pneumonia (cases) in low-income and middle-income countries. Physicians remotely classified recordings as crackles, wheeze or uninterpretable. Conventional and digital auscultation concordance was evaluated among 383 pneumonia cases with concurrently (within 2 hours) collected conventional and digital auscultation classifications using prevalence-adjusted bias-adjusted kappa (PABAK). Using an expanded set of 737 cases that also incorporated the non-concurrently collected assessments, we evaluated whether associations between auscultation classifications and clinical or aetiological findings differed between conventional or digital auscultation using χ2 tests and logistic regression adjusted for age, sex and site. RESULTS: Conventional and digital auscultation concordance was moderate for classifying crackles and/or wheeze versus neither crackles nor wheeze (PABAK=0.50), and fair for crackles-only versus not crackles-only (PABAK=0.30) and any wheeze versus no wheeze (PABAK=0.27). Crackles were more common on conventional auscultation, whereas wheeze was more frequent on digital auscultation. Compared with neither crackles nor wheeze, crackles-only on both conventional and digital auscultation was associated with abnormal chest radiographs (adjusted OR (aOR)=1.53, 95% CI 0.99 to 2.36; aOR=2.09, 95% CI 1.19 to 3.68, respectively); any wheeze was inversely associated with C-reactive protein >40 mg/L using conventional auscultation (aOR=0.50, 95% CI 0.27 to 0.92) and with very severe pneumonia using digital auscultation (aOR=0.67, 95% CI 0.46 to 0.97). Crackles-only on digital auscultation was associated with mortality compared with any wheeze (aOR=2.70, 95% CI 1.12 to 6.25). CONCLUSIONS: Conventional auscultation and remotely-classified digital auscultation displayed moderate concordance for presence/absence of wheeze and crackles among cases. Conventional and digital auscultation may provide different classification patterns, but wheeze was associated with decreased clinical severity on both.

Nocturnal survival of isoprene linked to formation of upper tropospheric organic aerosol.

Isoprene is emitted mainly by terrestrial vegetation and is the dominant volatile organic compound (VOC) in Earth's atmosphere. It plays key roles in determining the oxidizing capacity of the troposphere and the formation of organic aerosol. Daytime infrared satellite observations of isoprene reported here broadly agree with emission inventories, but we found substantial differences in the locations and magnitudes of isoprene hotspots, consistent with a recent study. The corresponding nighttime infrared observations reveal unexpected hotspots over tropical South America, the Congo basin, and Southeast Asia. We used an atmospheric chemistry model to link these nighttime isoprene measurements to low-NOx regions with high biogenic VOC emissions; at sunrise the remaining isoprene can lead to the production of epoxydiols and subsequently to the widespread seasonal production of organic aerosol in the tropical upper troposphere.

Vitamin D levels in Irish children with fractures: A prospective case-control study with 5 year follow-up.

INTRODUCTION: Twenty-five-hydroxy-vitamin D3 (25-OH-vit D) is a prohormone that is essential for normal calcium homeostasis and bone metabolism. Understanding its role is an important component of the proper care of the pediatric orthopaedic patient. The aim of this study was to determine whether children in Ireland with fractures have increased prevalence of 25-OH-Vit D deficiency compared with age matched controls and to ascertain the relationship between a low 25-OH-vit D level and the incidence of fractures in Irish children. We hypothesised that children presenting to our centre following a fracture would have significantly lower 25-OH-vit D. METHODS: A prospective case-control study at a large urban tertiary referral academic hospital located in Dublin, Ireland was completed over a 14 month period from June 2014 to August 2015. A total of 116 subjects, distributed as cases (n = 58) and controls (n = 58) were included in this study. Whole blood (10 ml) was taken in two serum bottles from each patient. Serum 25-hydroxy-vitamin D3 levels were measured. An age matched control group was generated from other children attending the hospital, who also had vitamin D levels measured for different clinical reasons. We followed up both the fracture and control group for the next 5 years to assess the repeat fracture rate. RESULTS: Fifty-eight patients with a fracture requiring operative intervention, were included in the study. Statistical analysis was performed comparing to 58 age and sex-matched controls. The mean vitamin D level for the fracture group was 63.2 nmol/L (SD = 27.3), which was higher than the mean of the controls (62.5 nmol/L) (SD = 21.3) (p = 0.86), but this difference was found not to be statistically significant in unadjusted analysis. There was no statistically significant difference in the number of patients classified with low serum Vitamin D levels (<50 nmolL), with the fracture group consisting of 22 (37.9%) patients, and the control group of 17 patients (29.3%) (p = 0.33) with a level below 50 nmol/L. At five-year follow-up, 11 of the 58 patients (18.9%) in the fracture group went on to have a further fracture compared with eight patients (13.7%) from the control group. Out of these 11 from the fracture group five (45.45%) had been found to have a low serum 25-OH-Vit D level five years previously. Out of the eight controls that presented with a fracture within the five-year period, 3 (37.5%) had had a low vitamin D level at the origin of this study. CONCLUSION: The results of this study show that children presenting to our institution with low energy fractures have a prevalence of 38% 25-hydroxy-vitamin D deficiency. This study included children from age 1 to 16 primarily Caucasian encompassing all fracture types resulting from accidental trauma. Our findings suggest that in an Irish pediatric population vitamin D status may impact fracture risk with more than one-third being deficient in this review.

Factors associated with graft survival in South African adolescent renal transplant patients at CMJAH over a 20-year period (GRAFT-SAT Study).

BACKGROUND: In the developed world, studies on transition of adolescent renal transplant patients have noted high rates of rejection, non-adherence and graft loss. There is a paucity of data in developing countries and none from South Africa. METHODS: We evaluated patient and graft outcomes during adolescence (10-19 years), of patients who received a renal transplant over a 20-year period (1990-2010), at a tertiary hospital in Johannesburg. Cox proportional hazards models and Kaplan-Meier curves were used to analyse graft and patient survival. RESULTS: A total of 213 kidney transplants were done in 162 patients during the study period, 165 transplants occurred during the adolescent period. Factors associated with graft failure on multivariate analysis included non-white race, transplant during the adolescent period ([aHR] 3.94; 95% [CI], 2.25-6.91), non-compliance with follow-up (aHR 3.89; 95% CI, 1.76-8.60) and receipt of a DD graft (aHR 2.10; 95% CI, 1.27-3.48). Patient survival rates at 1-, 3-, 5- and 10-years were 98.8%, 97.6%, 95.1% and 93.9% respectively. CONCLUSION: High rates of graft rejection and loss occurred in South African renal transplant recipients in the adolescent period, especially in those retained in paediatric care. Establishment of transition clinics may improve the graft outcomes of this vulnerable group and warrant further research.

Epidemiology and Seasonality of Endemic Human Coronaviruses in South African and Zambian Children: A Case-Control Pneumonia Study.

Endemic human coronaviruses (HCoV) are capable of causing a range of diseases from the common cold to pneumonia. We evaluated the epidemiology and seasonality of endemic HCoVs in children hospitalized with clinical pneumonia and among community controls living in countries with a high HIV burden, namely South Africa and Zambia, between August 2011 to October 2013. Nasopharyngeal/oropharyngeal swabs were collected from all cases and controls and tested for endemic HCoV species and 12 other respiratory viruses using a multiplex real-time PCR assay. We found that the likelihood of detecting endemic HCoV species was higher among asymptomatic controls than cases (11% vs. 7.2%; 95% CI: 1.2-2.0). This was however only observed among children > 6 months and was mainly driven by the Betacoronavirus endemic species (HCoV-OC43 and -HKU1). Endemic HCoV species were detected through the year; however, in Zambia, the endemic Betacoronavirus species tended to peak during the winter months (May-August). There was no association between HIV status and endemic HCoV detection.

The Etiology of Pneumonia in HIV-uninfected South African Children: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

BACKGROUND: Pneumonia is the major contributor to under 5 childhood mortality globally. We evaluated the etiology of pneumonia amongst HIV-uninfected South African children enrolled into the Pneumonia Etiology Research for Child Health case-control study. METHODS: Cases, 1-59 months of age hospitalized with World Health Organization clinically defined severe/very severe pneumonia, were frequency-matched by age and season to community controls. Nasopharyngeal-oropharyngeal swabs were analyzed using polymerase chain reaction for 33 respiratory pathogens, and whole blood was tested for pneumococcal autolysin. Cases were also tested for Mycobacterium tuberculosis. Population etiologic fractions (EF) of pneumonia with radiologic evidence of consolidation/infiltrate were derived for each pathogen through Bayesian analysis. RESULTS: Of the 805 HIV-uninfected cases enrolled based on clinical criteria, radiologically confirmed pneumonia was evident in 165 HIV-exposed, -uninfected, and 246 HIV-unexposed children. In HIV-exposed and HIV-unexposed children, respiratory syncytial virus was the most important pathogen with EFs of 31.6% [95% credible interval (CrI), 24.8%-38.8%] and 36.4% (95% CrI, 30.5%-43.1%), respectively. M. tuberculosis contributed EFs of 11.6% (95% CrI, 6.1%-18.8%) in HIV-exposed and 8.3% (95% CrI, 4.5%-13.8%) in HIV-unexposed children, including an EF of 16.3% (95% CrI, 6.1%-33.3%) in HIV-exposed children ≥12 months of age. Bacteremia (3.0% vs. 1.6%) and case fatality risk (3.6% vs. 3.7%) were similar in HIV-exposed and HIV-unexposed children. CONCLUSIONS: Vaccination strategies targeting respiratory syncytial virus should be prioritized for prevention of pneumonia in children. Furthermore, interventions are required to address the high burden of tuberculosis in the pathogenesis of acute community-acquired pneumonia in settings such as ours.

The Etiology of Pneumonia in HIV-1-infected South African Children in the Era of Antiretroviral Treatment: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

BACKGROUND: HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens. METHODS: Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques. RESULTS: Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25-146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The 'top 4' pathogens associated with radiologically confirmed pneumonia were Pneumocystis jirovecii [23.0%; 95% credible interval (CrI), 12.4%-31.5%], Staphylococcus aureus (10.6%; 95% CrI, 2.2%-20.2%), pneumococcus (9.5%; 95% CrI, 2.2%-18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%-14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease. CONCLUSIONS: Pneumocystis jirovecii, S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children.

Clinical Characteristics and Histopathology of Coronavirus Disease 2019-Related Deaths in African Children.

BACKGROUND: Globally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem. METHODS: Surveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution. RESULTS: SARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS. CONCLUSIONS: COVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children.

Correction to: Day-case pelvic osteotomy for developmental dysplasia of the hip.

[This corrects the article DOI: 10.1302/1863-2548.14.200164.].

Epidemiology of the Rhinovirus (RV) in African and Southeast Asian Children: A Case-Control Pneumonia Etiology Study.

Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1-59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries. Nasopharyngeal/oropharyngeal swabs were collected for all participants, combined, and tested for RV and 18 other respiratory viruses using the Fast Track multiplex real-time PCR assay. RV detection was more common among cases (24%) than controls (21%) (aOR = 1.5, 95%CI:1.3-1.6). This association was driven by the children aged 12-59 months, where 28% of cases vs. 18% of controls were RV-positive (aOR = 2.1, 95%CI:1.8-2.5). Wheezing was 1.8-fold (aOR 95%CI:1.4-2.2) more prevalent among pneumonia cases who were RV-positive vs. RV-negative. Of the RV-positive cases, 13% had a higher probability (>75%) that RV was the cause of their pneumonia based on the PERCH integrated etiology analysis; 99% of these cases occurred in children over 12 months in Bangladesh. RV was commonly identified in both cases and controls and was significantly associated with severe pneumonia status among children over 12 months of age, particularly those in Bangladesh. RV-positive pneumonia was associated with wheezing.