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.

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.

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.

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.

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.

In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors. METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32). CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

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.

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.

Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males. Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

Predominance of the Mycobacterium tuberculosis Beijing strain amongst children from a high tuberculosis burden township in South Africa.

The objective was to determine the molecular epidemiology and drug susceptibility patterns of Mycobacterium tuberculosis (MTB) of children and their household contacts (HHC) in Umlazi, a high TB-burden township in South Africa. Sixty eight MTBRifPLUS positive TB-infected children (TIC) (≤14 years) and 111 HHC were enrolled. Drug susceptibility testing (DST) was performed on sputum samples using the proportion method and GenoType® MTBDR. Genotyping of MTB was conducted using IS6110-restriction fragment length polymorphism (RFLP) and spoligotyping. Rifampicin (RIF) susceptibility was observed in 67/68 TIC. GenoType® MTBDRplus and phenotypic DST identified drug resistant strains in five of 16 culture-confirmed TIC. The Beijing strain was identified in six and the F15/LAM4/KZN strain in one of the 13 TIC respectively. Four patients with unknown RFLP strains belonged to spoligoclades S, T1, T3 variant and X2. The S-lineage and an unknown strain were identified in two HHC. MDR-TB and pre-XDR-TB were identified in one HHC each. Household transmission could not be determined as none of the culture-confirmed TIC resided with the six culture-confirmed contacts. The predominance of the hypervirulent Beijing strain and presence of drug-resistant strains must be considered in the implementation of effective TB control strategies and development of efficacious vaccines.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries.

IMPORTANCE: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent. OBJECTIVE: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection. EXPOSURES: Age, sex, preexisting comorbidities, and region of residence. MAIN OUTCOMES AND MEASURES: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay. RESULTS: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge. CONCLUSIONS AND RELEVANCE: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.

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.

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.

Management of acute fever in children: Consensus recommendations for community and primary healthcare providers in sub-Saharan Africa.

Fever is one of the most common reasons for unwell children presenting to pharmacists and primary healthcare practitioners. Currently there are no guidelines for assessment and management of fever specifically for community and primary healthcare workers in the sub-Saharan Africa region. This multidisciplinary consensus guide was developed to assist pharmacists and primary healthcare workers in sub-Saharan Africa to risk stratify and manage children who present with fever, decide when to refer, and how to advise parents and caregivers. Fever is defined as body temperature ≥ 37.5 °C and is a normal physiological response to illness that facilitates and accelerates recovery. Although it is often associated with self-limiting illness, it causes significant concern to both parents and attending healthcare workers. Clinical signs may be used by pharmacy staff and primary healthcare workers to determine level of distress and to distinguish between a child with fever who is at high risk of serious illness and who requires specific treatment, hospitalisation or specialist care, and those at low risk who could be managed conservatively at home. In children with warning signs, serious causes of fever that may need to be excluded include infections (including malaria), non-infective inflammatory conditions and malignancy. Simple febrile convulsions are not in themselves harmful, and are not necessarily indicative of serious infection. In the absence of illness requiring specific treatment, relief from distress is the primary indication for prescribing pharmacotherapy, and antipyretics should not be administered with the sole intention of reducing body temperature. Care must be taken not to overdose medications and clear instructions should be given to parents/caregivers on managing the child at home and when to seek further medical care.

Effects of prenatal exposure factors on birth outcomes through mediation of favorable fetal growth conditions using structural equation modeling.

BACKGROUND: Birth weight, birth length, and gestational age are major indicators of newborn health. Several prenatal exposure factors influence the fetal environment. The aim of the study was to investigate the effect of prenatal exposure factors, including socio-demographic, behavioural, dietary, physical activity, clinical and environmental on birth outcomes through the mediation of Favourable Fetal Growth Conditions (FFGC). METHODS: Data was obtained from six hundred and fifty-six Mother and Child in the Environment birth cohort study in Durban, South Africa from 2013 to 2017. We adopted structural equation models which evaluate the direct and indirect effects by allowing multiple simultaneous equations to incorporate confounding and mediation. RESULTS: A significant direct and indirect effect of FFGC on newborn weight, length, and gestational age was seen. Gestational weight gain and maternal body mass index in the first trimester exerted a mediation effect between maternal behavioural risk factors and FFGC. Similarly, the level of physical activity during pregnancy was associated with decreased gestational weight gain. The effects of maternal characteristics on newborn weight, length, and gestational age were largely indirect, operating through FFGC as a latent variable. CONCLUSIONS: Gestational weight gain and maternal pre-gestational BMI were observed to mediate the association between prenatal behavioural risk factors and favourable fetal growth conditions. TRIAL REGISTRATION: Retrospectively registered from 01 March 2013.

Validation of visual estimation of neonatal jaundice in low-income and middle-income countries: a multicentre observational cohort study.

OBJECTIVE: Determine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia. DESIGN: Multicentre observational cohort study. SETTING: Hospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivia. PARTICIPANTS: Neonates aged 1-20 days (n=2642) who presented to hospitals for evaluation of acute illness. Infants referred for any reason from another health facility or those needing immediate cardiopulmonary resuscitation were excluded. OUTCOME MEASURES: Infants were evaluated for distribution (head, trunk, distal extremities) and degree (mild, moderate, severe) of jaundice by PHWs and physicians. Serum bilirubin level was determined for infants with jaundice, and analyses of sensitivity and specificity of visual estimations of jaundice used bilirubin thresholds of >260 µmol/L (need for phototherapy) and >340 µmol/L (need for emergency intervention in at-risk and preterm babies). RESULTS: 1241 (47.0%) neonates had jaundice. High sensitivity for detecting neonates with serum bilirubin >340 µmol/L was found for 'any jaundice of the distal extremities (palms or soles) OR deep jaundice of the trunk or head' for both PHWs (89%-100%) and physicians (81%-100%) across study sites; specificity was more variable. 'Any jaundice of the distal extremities' identified by PHWs and physicians had sensitivity of 71%-100% and specificity of 55%-95%, excluding La Paz. For the bilirubin threshold >260 µmol/L, 'any jaundice of the distal extremities OR deep jaundice of the trunk or head' had the highest sensitivity across sites (PHWs: 58%-93%, physicians: 55%-98%). CONCLUSIONS: In settings where serum bilirubin cannot be measured, neonates with any jaundice on the distal extremities should be referred to a hospital for evaluation and management, where delays in serum bilirubin measurement and appropriate treatment are anticipated following referral, the higher sensitivity sign, any jaundice on the distal extremities or deep jaundice of the trunk or head, may be preferred.

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.

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.