Environmental exposures associated with early childhood recurrent wheezing in the mother and child in the environment birth cohort: a time-to-event study.

BACKGROUND: Antenatal factors and environmental exposures contribute to recurrent wheezing in early childhood. AIM: To identify antenatal and environmental factors associated with recurrent wheezing in children from birth to 48 months in the mother and child in the environment cohort, using time-to-event analysis. METHOD: Maternal interviews were administered during pregnancy and postnatally and children were followed up from birth to 48 months (May 2013-October 2019). Hybrid land-use regression and dispersion modelling described residential antenatal exposure to nitrogen dioxide (NO2) and particulate matter of 2.5 µm diameter (PM2.5). Wheezing status was assessed by a clinician. The Kaplan-Meier hazard function and Cox-proportional hazard models provided estimates of risk, adjusting for exposure to environmental tobacco smoke (ETS), maternal smoking, biomass fuel use and indoor environmental factors. RESULTS: Among 520 mother-child pairs, 85 (16%) children, had a single wheeze episode and 57 (11%) had recurrent wheeze. Time to recurrent wheeze (42.9 months) and single wheeze (37.8 months) among children exposed to biomass cooking fuels was significantly shorter compared with children with mothers using electricity (45.9 and 38.9 months, respectively (p=0.03)). Children with mothers exposed to antenatal ETS were 3.8 times more likely to have had recurrent wheeze compared with those not exposed (adjusted HR 3.8, 95% CI 1.3 to 10.7). Mean birth month NO2 was significantly higher among the recurrent wheeze category compared with those without wheeze. NO2 and PM2.5 were associated with a 2%-4% adjusted increased wheezing risk. CONCLUSION: Control of exposure to ETS and biomass fuels in the antenatal period is likely to delay the onset of recurrent wheeze in children from birth to 48 months.

A Review Of Host-Specific Diagnostic And Surrogate Biomarkers In Children With Pulmonary Tuberculosis.

BACKGROUND: Tuberculosis (TB) is one of the most common causes of mortality globally with a steady rise in paediatric cases in the past decade. Laboratory methods of diagnosing TB and monitoring response to treatment have limitations. Current research focuses on interrogating host- and/or pathogen-specific biomarkers to address this problem. METHODS: We reviewed the literature on host-specific biomarkers in TB to determine their value in diagnosis and treatment response in TB infected and HIV/TB co-infected children on anti-tuberculosis treatment. RESULTS AND CONCLUSION: While no single host-specific biomarker has been identified for diagnosis or treatment responses in children, several studies suggest predictive biosignatures for disease activity. Alarmingly, current data on host-specific biomarkers for diagnosing and assessing anti-tuberculosis treatment in TB/HIV co-infected children is inadequate. Various factors affecting host-specific biomarker responses should be considered in interpreting findings and designing future studies within specific clinical settings.

T cell derived HIV-1 is present in the CSF in the face of suppressive antiretroviral therapy.

HIV cerebrospinal fluid (CSF) escape, where HIV is suppressed in blood but detectable in CSF, occurs when HIV persists in the CNS despite antiretroviral therapy (ART). To determine the virus producing cell type and whether lowered CSF ART levels are responsible for CSF escape, we collected blood and CSF from 156 neurosymptomatic participants from Durban, South Africa. We observed that 28% of participants with an undetectable HIV blood viral load showed CSF escape. We detected host cell surface markers on the HIV envelope to determine the cellular source of HIV in participants on the first line regimen of efavirenz, emtricitabine, and tenofovir. We confirmed CD26 as a marker which could differentiate between T cells and macrophages and microglia, and quantified CD26 levels on the virion surface, comparing the result to virus from in vitro infected T cells or macrophages. The measured CD26 level was consistent with the presence of T cell produced virus. We found no significant differences in ART concentrations between CSF escape and fully suppressed individuals in CSF or blood, and did not observe a clear association with drug resistance mutations in CSF virus which would allow HIV to replicate. Hence, CSF HIV in the face of ART may at least partly originate in CD4+ T cell populations.

Impact of ambient air pollution exposure during pregnancy on adverse birth outcomes: generalized structural equation modeling approach.

BACKGROUND: Air pollution and several prenatal factors, such as socio-demographic, behavioural, physical activity and clinical factors influence adverse birth outcomes. The study aimed to investigate the impact of ambient air pollution exposure during pregnancy adjusting prenatal risk factors on adverse birth outcomes among pregnant women in MACE birth cohort. METHODS: Data for the study was obtained from the Mother and Child in the Environment (MACE) birth cohort study in Durban, South Africa from 2013 to 2017. Land use regression models were used to determine household level prenatal exposure to PM2.5, SO2 and NOx. Six hundred and fifty-six births of pregnant females were selected from public sector antenatal clinics in low socio-economic neighbourhoods. We employed a Generalised Structural Equation Model with a complementary log-log-link specification. RESULTS: After adjustment for potential prenatal factors, the results indicated that exposure to PM2.5 was found to have both significant direct and indirect effects on the risk of all adverse birth outcomes. Similarly, an increased level of maternal exposure to SO2 during pregnancy was associated with an increased probability of being small for gestational age. Moreover, preterm birth act a mediating role in the relationship of exposure to PM2.5, and SO2 with low birthweight and SGA. CONCLUSIONS: Prenatal exposure to PM2.5 and SO2 pollution adversely affected birth outcomes after controlling for other prenatal risk factors. This suggests that local government officials have a responsibility for better control of air pollution and health care providers need to advise pregnant females about the risks of air pollution during pregnancy.

Maternal exposure to indoor PM2.5 and associated adverse birth outcomes in low socio-economic households, Durban, South Africa.

The association between in utero exposure to indoor PM2.5 and birth outcomes is not conclusive. We assessed the association between in utero exposure to indoor PM2.5 , birth weight, gestational age, low birth weight, and/or preterm delivery. Homes of 800 pregnant women were assessed using a structured walkthrough questionnaire. PM2.5 measurements were undertaken in 300 of the 800 homes for a period of 24 h. Repeated sampling was conducted in 30 of these homes to determine PM2.5 predictors that can reduce within-and/or between-home variability. A predictive model was used to estimate PM2.5 levels in unmeasured homes (n = 500). The mean (SD) for PM2.5 was 37 µg/m3 (29) with a median of 28µg/m3 . The relationship between PM2.5 exposure, birth weight, gestational age, low birth weight, and preterm delivery was assessed using multivariate linear and logistic regression models. We explored infant sex as a potential effect modifier, by creating an interaction term between PM2.5 and infant sex. The odds ratio of low birth weight and preterm delivery was 1.75 (95%CI: 1.47, 2.09) and 1.21 (95%CI: 1.06, 1.39), respectively, per interquartile increase (18 µg/m3 ) in PM2.5 exposure. The reduction in birth weight and gestational age was 75 g (95%CI: 107.89, 53.15) and 0.29 weeks (95%CI: 0.40, 0.19) per interquartile increase in PM2.5 exposure. Infant sex was an effect modifier for PM2.5 on birth weight and gestational age, and the reduction in birth weight and gestational age was 103 g (95%CI: 142.98, 64.40) and 0.38 weeks (95% CI: 0.53, 0.23), respectively, for boys, and 54 g (95%CI: 91.78,15.62) and 0.23 weeks (95%CI:0.37, 0.08), respectively, for girls. Exposure to PM2.5 is associated with adverse pregnancy outcomes. To protect the population during their reproductive period, public health policy should focus on indoor PM2.5 levels.

The spatial modification of the non-linear effects of ambient oxides of nitrogen during pregnancy on birthweight in a South African birth cohort.

Birthweight is strongly associated with infant mortality and is a major determinant of infant survival. Several factors such as maternal, environmental, clinical, and social factors influence birthweight, and these vary geographically, including across low, middle, and economically advanced countries. The aim of the study was to investigate the geographical modification of the effect of oxides of nitrogen exposure on birthweight adjusted for clinical and socio-demographic factors. Data for the study was obtained from the Mother and Child in the Environment birth cohort study in Durban, South Africa. Pregnant females were selected from public sector antenatal clinics in low socioeconomic neighborhoods. Land use regression models were used to determine household level antenatal exposure to oxides of nitrogen (NOx). Six hundred and seventy-seven births were analysed, using the geoadditive model with Gaussian distribution and identity link function. The newborns in the cohort had a mean birthweight of 3106.5 g (standard deviation (SD): 538.2 g and the maternal mean age was 26.1 years (SD: 5.7). A spatially modified NOx exposure-related effect on birthweight was found across two geographic regions in Durban. Prenatal exposure to NOx was also found to have a non-linear effect on the birthweight of infants. The study suggested that incorporating spatial variability is important to understand and design appropriate policies to reduce air pollution in order to prevent risks associated with birthweight.

Maternal demographic and antenatal factors, low birth weight and preterm birth: findings from the mother and child in the environment (MACE) birth cohort, Durban, South Africa.

BACKGROUND: Low birthweight (LBW) and preterm birth (PB) remain the leading cause of morbidity and mortality in neonates worldwide. The aim of this study was to identify maternal demographic and antenatal factors associated with PB and LBW among low socio-economic communities. METHODS: Pregnant women (n = 1099) were recruited in the first trimester into the Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa. Maternal factors such as demographic information, health status, residential area, occupational, personal and environmental smoking and biomass fuel use were obtained through standardised interviews, while clinical status was obtained in each trimester and antenatal information on HIV status and treatment, syphilis and conditions such as pregnancy induced hypertension, diabetes etc. was extracted from the antenatal assessments. Key outcomes of interest were preterm birth and low birthweight. The latter data was obtained from the clinical assessments performed by midwives at delivery. Logistic regression models identified factors associated with PB and LBW. RESULTS: Of the 760 live births, 16.4 and 13.5% were preterm and LBW, respectively. Mothers who delivered by caesarean section had an increased odds of having LBW babies (Adjusted odds ratio (AOR): 1.7; 95% CI: 1.1-2.7) and PB (AOR: 1.7, 95% CI: 1.1-2.7) versus normal vaginal deliveries. Mothers > 30 years (AOR: 1.8, 95% CI: 1.1-2.9) and current smokers (AOR: 2.7, 95% CI: 1.3-5.8) had an increased odds of having PB babies. Compared to younger mothers and non-smokers respectively. An effect of PB and LBW was seen among mothers with high BMI (25.0-29.9 kg/m2) (PB: AOR: 0.5, 95% CI: 0.3-0.9 and LBW: AOR: 0.5, 0.5, CI: 0.3-0.8), and obese BMI (> 30 kg/m2) (PB: AOR: 0.5, 95% CI: 0.3-0.9 and LBW: AOR: 0.4, CI: 0.2-0.7). Maternal HIV (PB AOR: 1.4 and LBW AOR: 1.2) and history of sexually transmitted infections (PB AOR: 2.7 and LBW AOR: 4.2) were not statistically significant. CONCLUSION: Maternal age, cigarette smoking and caesarean delivery were associated with LBW and PB. Findings highlight the need of maternal health interventions to improve new-born health outcomes.

The differential effect of maternal dietary patterns on quantiles of Birthweight.

BACKGROUND: Maternal dietary habits during pregnancy are considered essential for development and growth of the fetus as well as maternal health. It has an effect on the birthweight of infants. However, little is known about the effect of dietary patterns on birthweight in urban South Africa. This study aimed to investigate differential effect of dietary patterns of pregnant women on quantiles of birthweight. METHODS: Data for the study were obtained from a Mother and Child in the Environment birth cohort study in Durban South Africa. Quantile regression was used to investigate the effect of maternal dietary patterns on quantiles of birthweight. Data collection was conducted during the period of 2013 to 2017 in Durban South Africa. Using factor analysis, eight dietary groups were identified from 687 pregnant women in the cohort. Quantile regression analysis was employed to identify the differential effects of the seven dietary groups and demographic factors on the birthweight. RESULTS: The quantile regression estimates at the 50th quantile and the ordinary regression estimates painted the same picture about the conditional mean effect of covariates on the birthweight. But unlike the quantile regression the ordinary regression fails to give insights about the covariates effect disparities at the low and/or upper birthweight quantiles. All the dietary groups show a significant differential effect at different birthweight quantiles. For instance, increased frequency of protein rich foods intake was associated with reduction in birthweight at lower and upper quantiles; increased frequency of junk foods intake has a slight increase in birthweight at the lower quantiles but significantly higher increase at the 95th quantile (p < 0.001); increase in consuming vegetable rich foods, reduced birthweight at 95th quantile (p < 0.001). The results further showed that employment (p = 0.006) and family size (p = 0.002) had differential effects across different birthweight quantiles. CONCLUSIONS: Both maternal undernutrition and overnutrition of protein rich foods, junk foods, snack and energy foods and vegetable rich foods have shown a substantial varying effects on those infants with birthweights in the lower and upper birthweight quantiles.

Association of childhood pulmonary tuberculosis with exposure to indoor air pollution: a case control study.

BACKGROUND: Crude measures of exposure to indicate indoor air pollution have been associated with the increased risk for acquiring tuberculosis. Our study aimed to determine an association between childhood pulmonary tuberculosis (PTB) and exposure to indoor air pollution (IAP), based on crude exposure predictors and directly sampled and modelled pollutant concentrations. METHODS: In this case control study, children diagnosed with PTB were compared to children without PTB. Questionnaires about children's health; and house characteristics and activities (including household air pollution) and secondhand smoke (SHS) exposure were administered to caregivers of participants. A subset of the participants' homes was sampled for measurements of PM10 over a 24-h period (n = 105), and NO2 over a period of 2 to 3 weeks (n = 82). IAP concentrations of PM10 and NO2 were estimated in the remaining homes using predictive models. Logistic regression was used to look for association between IAP concentrations, crude measures of IAP, and PTB. RESULTS: Of the 234 participants, 107 were cases and 127 were controls. Pollutants concentrations (µg/m3) for were PM10 median: 48 (range: 6.6-241) and NO2 median: 16.7 (range: 4.5-55). Day-to-day variability within- household was large. In multivariate models adjusted for age, sex, socioeconomic status, TB contact and HIV status, the crude exposure measures of pollution viz. cooking fuel type (clean or dirty fuel) and SHS showed positive non-significant associations with PTB. Presence of dampness in the household was a significant risk factor for childhood TB acquisition with aOR of 2.4 (95% CI: 1.1-5.0). The crude exposure predictors of indoor air pollution are less influenced by day-to-day variability. No risk was observed between pollutant concentrations and PTB in children for PM10 and NO2. CONCLUSION: Our study suggests increased risk of childhood tuberculosis disease when children are exposed to SHS, dirty cooking fuel, and dampness in their homes. Yet, HIV status, age and TB contact are the most important risk factors of childhood PTB in this population.

Clinical utility of bronchoalveolar lavage cytomegalovirus viral loads in the diagnosis of cytomegalovirus pneumonitis in infants.

Cytomegalovirus (CMV) pneumonitis is a significant cause of morbidity and mortality of children in Africa. The current practice for diagnosing CMV pneumonitis in this setting is based on interpretation of clinical, laboratory, and radiological findings. There is a need for a sensitive and specific laboratory test to objectively distinguish between patients with CMV pneumonitis and those with CMV infection, and non-CMV pneumonia. In this study, we compared plasma and non-bronchoscopic bronchoalveolar lavage (NBBAL) CMV viral loads in patients with CMV pneumonitis and those with CMV infection and non-CMV pneumonia. Receiver operator characteristic curve analysis was used to establish a threshold and assess utility of viral loads in the diagnosis of CMV pneumonitis. We assessed the urea dilution method, and expression of viral loads relative to the total amount of extracted nucleic acids in correcting for NBBAL dilution. CMV quantification in NBBAL specimens was more predictive of CMV pneumonitis than blood CMV quantification. The threshold of 4.03 log IU/ml in NBBAL specimens has good predictive value and can be used to guide management of infants with suspected CMV pneumonitis. Adjusting for dilution of NBBAL specimens by using the urea dilution method or by expressing the viral load relative to the total nucleic acids extracted did not provide additional analytical benefits. J. Med. Virol. 89:1080-1087, 2017. © 2016 Wiley Periodicals, Inc.

Indoor air quality of low and middle income urban households in Durban, South Africa.

INTRODUCTION: Elevated levels of indoor air pollutants may cause cardiopulmonary disease such as lower respiratory infection, chronic obstructive lung disease and lung cancer, but the association with tuberculosis (TB) is unclear. So far the risk estimates of TB infection or/and disease due to indoor air pollution (IAP) exposure are based on self-reported exposures rather than direct measurements of IAP, and these exposures have not been validated. OBJECTIVE: The aim of this paper was to characterize and develop predictive models for concentrations of three air pollutants (PM10, NO2 and SO2) in homes of children participating in a childhood TB study. METHODS: Children younger than 15 years living within the eThekwini Municipality in South Africa were recruited for a childhood TB case control study. The homes of these children (n=246) were assessed using a walkthrough checklist, and in 114 of them monitoring of three indoor pollutants was also performed (sampling period: 24h for PM10, and 2-3 weeks for NO2 and SO2). Linear regression models were used to predict PM10 and NO2 concentrations from household characteristics, and these models were validated using leave out one cross validation (LOOCV). SO2 concentrations were not modeled as concentrations were very low. RESULTS: Mean indoor concentrations of PM10 (n=105), NO2 (n=82) and SO2 (n=82) were 64µg/m3 (range 6.6-241); 19µg/m3 (range 4.5-55) and 0.6µg/m3 (range 0.005-3.4) respectively with the distributions for all three pollutants being skewed to the right. Spearman correlations showed weak positive correlations between the three pollutants. The largest contributors to the PM10 predictive model were type of housing structure (formal or informal), number of smokers in the household, and type of primary fuel used in the household. The NO2 predictive model was influenced mostly by the primary fuel type and by distance from the major roadway. The coefficients of determination (R2) for the models were 0.41 for PM10 and 0.31 for NO2. Spearman correlations were significant between measured vs. predicted PM10 and NO2 with coefficients of 0.66 and 0.55 respectively. CONCLUSION: Indoor PM10 levels were relatively high in these households. Both PM10 and NO2 can be modeled with a reasonable validity and these predictive models can decrease the necessary number of direct measurements that are expensive and time consuming.

Subtherapeutic concentrations of first-line anti-TB drugs in South African children treated according to current guidelines: the PHATISA study.

OBJECTIVES: There is a paucity of evidence regarding the optimal dosing of anti-TB drugs in children. The aim of this study was to identify the pharmacokinetic parameters of first-line anti-TB drugs and the concentrations achieved after implementation of the 2010 WHO-recommended paediatric dosages. METHODS: We conducted a prospective, observational pharmacokinetic study in children 10 years old or younger who were on isoniazid, rifampicin, pyrazinamide and ethambutol therapy in Durban, KwaZulu-Natal, South Africa. Blood was collected at six timepoints over a 24 h period, chosen using optimal sampling theory. The drug concentrations were simultaneously modelled to identify the compartmental pharmacokinetics of each drug in each child, using the ADAPT program. RESULTS: The best six sampling timepoints in children were identified as 0 (pre-dose) and 0.42, 1.76, 3.37, 10.31 and 24 h post-dose. Thirty-one children were recruited and blood was drawn at these timepoints. Rifampicin, ethambutol and pyrazinamide were best described using a one-compartment model, while isoniazid was best described with a two-compartment model. Only 2/31 (6%), 20/31 (65%), 17/31 (55%) and 2/13 (15%) of children attained the WHO 2 h target therapeutic concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. Moreover, only 24/31 (77%), 6/31 (19%) and 8/31 (26%) achieved the AUCs associated with an optimal clinical response to rifampicin, pyrazinamide and isoniazid, respectively. No single risk factor was significantly associated with below-normal drug levels. CONCLUSIONS: The drug concentrations of all first-line anti-TB drugs were markedly below the target therapeutic concentrations in most South African children who received the revised WHO-recommended paediatric weight-based dosages.

Stunting is associated with poor outcomes in childhood pneumonia.

OBJECTIVE: Stunting affects 26.7% of children worldwide, and little is known about its effects on the outcomes of childhood pneumonia. We evaluated the effect of stunting on the outcomes of pneumonia among children enrolled in two large clinical trials. METHODS: We analysed data from two WHO and USAID-sponsored inpatient treatment trials, the Severe Pneumonia Evaluation Antimicrobial Research study (n = 958) and the Amoxicillin Penicillin Pneumonia International Study (n = 1702), which enrolled children aged 2-59 months across 16 sites in LMICs. We assessed the effect of stunting (height-for-age Z score < -2) on treatment outcome and time to resolution of hypoxaemic pneumonia. RESULTS: Among 2542 (96%) children with valid data for height, 28% were stunted and 12.8% failed treatment by 5 days. The failure rate among stunted patients was 16.0% vs. 11.5% among non-stunted patients [unadjusted RR = 1.24 (95% CI 1.08, 1.41); adjusted RR = 1.28 (95% CI 1.10, 1.48)]. An inverse relationship was observed between height and failure rates, even among non-stunted children. Among 845 patients with hypoxaemic pneumonia, stunting was associated with a lower probability of normalisation of respiratory rate [HR = 0.63 (95% CI 0.52, 0.75)] and oxygen saturation [HR = 0.74 (95% CI 0.61, 0.89)]. CONCLUSIONS: Stunting increases the risk of treatment failure and is associated with a longer course of recovery in children with pneumonia. Strategies to decrease stunting may decrease the burden of adverse outcomes in childhood pneumonia in low-resource settings.

The role of interferon gamma release assays in the monitoring of response to anti-tuberculosis treatment in children.

Successful control of childhood TB requires early diagnosis, effective chemotherapy and a method of evaluating the response to therapy. Identification of suitable biomarkers that predict the response to anti-TB therapy may allow the duration of treatment to be shortened. The majority of biomarker studies in paediatric TB have focused on the role of T cell-based interferon-gamma (IFN-γ) release assays (IGRAs) in the diagnosis of either latent or active disease. Little has been published on the role of IGRAs in the monitoring response to therapy in children. We reviewed the available literature to ascertain the value of IGRAs in the monitoring of response to anti-TB therapy in children. We explored the results of the few studies that have investigated the role of IGRAs as markers of response to anti-TB treatment in children. We conclude that the role of IGRAs as surrogate markers appears promising. Robust clinical trials are, however, needed to entrench the value of IGRAs as surrogate biomarkers of response to anti-TB therapy in children.

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.

Lung infiltrates in antiretroviral-naive HIV-infected children with chronic lung disease: value of non-bronchoscopic bronchoalveolar lavage in the detection of Candida albicans.

OBJECTIVE: To describe the etiology of lung infiltrates in HIV-infected antiretroviral-naive children with chronic persistent/recurrent lung disease in whom routine cultures were negative and were non-responders to World Health Organization standard antimicrobial therapy. METHOD: Non-bronchoscopic bronchoalveolar lavage (NBBAL) was performed on these non-responders. RESULTS: Fifty children were enrolled. Single isolates on NBBAL were seen in 28 cases, dual pathogens in 5 cases and no growth in 14 cases. Haemophilus influenzae (n = 12), Candida albicans (n = 5) and Mycobacterium spp. other than tuberculosis (n = 4) were the commonest pathogens seen. Eight cases with no growth had segmental or lobar collapse: in five cases, NBBAL was therapeutic and in two cases, a diagnosis of lymphoma was made on open lung biopsy. Thirty-two of the 38 cases (84%) had favorable outcomes on follow-up. CONCLUSION: Haemophilus influenzae, C. albicans and Mycobacterium spp. other than tuberculosis are important pathogens in children with HIV and HIV-associated chronic lung disease.

Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection in KwaZulu-Natal, South Africa.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been infrequently described in Africa. OBJECTIVE: To describe the clinical characteristics, outcomes and associations of severe disease in children hospitalized with MIS-C in KwaZulu-Natal. METHODS: Retrospective multicenter study of children (0-13 years) who met the Centers for Disease Control and Prevention criteria for MIS-C. Children with shock were compared with children without shock to determine the characteristics of severe MIS-C. RESULTS: Twenty-nine children with MIS-C were identified, the mean age was 55 (SD ±45) months, 25 (86%) were Black-African, and 8 (28%) had pre-existing comorbidities. The predominant presenting symptoms included fever 29 (100%), gastrointestinal symptoms 25 (83%), skin rash 19 (65%), and shock 17 (59%). Children with shock had significantly increased CRP (P = 0.01), ferritin (P < 0.001), troponin-T (P = 0.02), B-type natriuretic peptide (BNP) (P = 0.01), and lower platelets (P = 0.01). Acute kidney injury (P = 0.01), cardiac involvement (P = 0.02), and altered levels of consciousness (P = 0.03) were more common in children with shock. The median length of hospital stay was 11 (IQR 7-19) days, with a mortality of 20.6%. Children who did not survive had significantly higher ferritin levels 1593 (IQR 1069-1650) ng/mL versus 540 (IQR 181-1156) ng/mL; P = 0.03) and significantly more required mechanical ventilation (OR 18; confidence interval 1.7-191.5; P = 0.005). CONCLUSIONS: Hospitalized children with MIS-C in KwaZulu-Natal had more aggressive disease and higher mortality than children in better-resourced settings. Markedly elevated biomarkers and critical organ involvement were associated with severe disease. Risk factors for poor outcomes include higher ferritin levels and the need for mechanical ventilation.

Bronchiolitis versus bronchopneumonia: navigating antibiotic use within the LRTI spectrum.

Bronchiolitis, a common reason for infant hospitalisation in South Africa (SA), is caused by viral pathogens. Bronchiolitis is typically an illness of mild to moderate severity that occurs in well-nourished children. Hospitalised SA infants frequently have severe disease and/or coexisting medical conditions, and these cases of bronchiolitis may have bacterial co-infection that requires antibiotic therapy. However, the existence of widespread antimicrobial resistance in SA warrants the judicious use of antibiotics. This commentary describes: (i) common clinical pitfalls leading to an incorrect diagnosis of bronchopneumonia; and (ii) considerations for antibiotic therapy in hospitalised infants with bronchiolitis. If antibiotics are prescribed, the indication for their use should be clearly stated, and antibiotic therapy must be stopped promptly if investigations indicate that bacterial co-infection is unlikely. Until more robust data emerge, we recommend a pragmatic management strategy to inform antibiotic use in hospitalised SA infants with bronchiolitis in whom bacterial co-infection is suspected.

Predictors associated with critical care need and in-hospital mortality among children with laboratory-confirmed COVID-19 infection in a high HIV infection burden region.

Introduction: Despite the extra mortality associated with COVID-19 death globally, there is scant data on COVID-19-related paediatric mortality in Sub-Saharan Africa. We assessed predictors of critical care needs and hospital mortality in South African children with laboratory-confirmed SARS-CoV-2 infection in region with high HIV infection burden. Methods: We conducted a secondary multicentre analysis of the AFREhealth cohort (a multinational, multicentre cohort of paediatric COVID-19 clinical outcomes across six African countries) of children admitted to the Inkosi Albert Luthuli, a quaternary hospital in KwaZulu-Natal, South Africa, with confirmed RT-PCR between March 2020 and December 2020. We constructed multivariable logistic regression to explore factors associated with the need for critical care (high care/ intensive care hospitalisation or oxygen requirement) and cox-proportional hazards models to further assess factors independently associated with in-hospital death. Results: Of the 82 children with PCR-confirmed SARS-CoV-2 infection (mean ± SD age: 4.2 ± 4.4 years), 35(42.7%) were younger than one year, 52(63%) were female and 59(71%) had a pre-existing medical condition. Thirty-seven (45.2%) children required critical care (median (IQR) duration: 7.5 (0.5-13.5) days) and 14(17%) died. Independent factors associated with need for critical care were being younger than 1 year (aPR: 3.02, 95%CI: 1.05-8.66; p = 0.04), having more than one comorbidity (aPR: 2.47, 95%CI: 1.32-4.61; p = 0.004), seizure (aPR: 2.39, 95%CI: 1.56-3.68; p < 0.001) and impaired renal function. Additionally, independent predictors of in-hospital mortality were exposure to HIV infection (aHR: 6.8, 95%CI:1.54-31.71; p = 0.01), requiring invasive ventilation (aHR: 3.59, 95%CI: 1.01-12.16, p = 0.048) and increase blood urea nitrogen (aHR: 1.06, 95%CI: 1.01-1.11; p = 0.017). However, children were less likely to die from COVID-19 if they were primarily admitted to quaternary unit (aHR: 0.23, 95%CI: 0.1-0.86, p = 0.029). Conclusion: We found a relatively high hospital death rate among children with confirmed COVID-19. During COVID-19 waves, a timely referral system and rapid identification of children at risk for critical care needs and death, such as those less than one year and those with comorbidities, could minimize excess mortality, particularly in high HIV-infection burden countries.

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.