Role of Pediatricians in Promoting and Supporting Breastfeeding: A Position Paper of the International Pediatric Association Strategic Advisory Group on Infant, Child, and Adolescent Nutrition.

BACKGROUND: Promoting and supporting breastfeeding is an important public health intervention with multiple benefits for both infants and mothers. Even modest increases in the prevalence and duration of breastfeeding could significantly reduce healthcare costs and improve maternal and child health outcomes. However, widespread adoption of breastfeeding recommendations remains poor in most settings, which contributes to widening health and social inequalities. Pediatricians have a duty to advocate for improving child health, including promoting and supporting breastfeeding. SUMMARY: This paper, from the International Pediatric Association Special Advisory Group on Nutrition, considers common barriers to breastfeeding and addresses how pediatricians can better promote and support breastfeeding, both at an individual level and by influencing practice and policy. All pediatricians need to understand the basics of breastfeeding, including lactation physiology, recognize common breastfeeding problems, and advise mothers or refer them for appropriate support; training curricula for general pediatricians and all pediatric subspecialties should reflect this. Even in the situation where their day-to-day work does not involve direct contact with mothers and infants, pediatricians can have an important influence on policy and practice. They should support colleagues who work directly with mothers and infants, ensuring that systems and environments are conducive to breastfeeding and, where appropriate, milk expression. Pediatricians and pediatric organizations should also promote policies aimed at promoting and supporting breastfeeding at local, regional, national, and international levels. KEY MESSAGES: Pediatricians have a duty to promote and support breastfeeding, regardless of their day-to-day role and responsibilities. Pediatric training curricula should ensure that all trainees acquire a good understanding of breastfeeding so they are able to effectively support mothers in their personal practice but also influence breastfeeding practice and policy at a local, regional, national, and international level.

Liver transient elastography values in healthy South African children.

BACKGROUND: Transient elastography (TE) is a rapid noninvasive ultrasound-based technology that measures liver stiffness as a surrogate for liver fibrosis and controlled attenuation parameter (CAP) as a measure of liver steatosis. However, normal ranges in children are not well defined in all populations. The aim of this study was to determine transient elastography values in healthy South African children. METHODS: From April 2019 to December 2021, children were recruited from the HIV negative control group of a cohort study. Only children neither overweight nor obese, without evidence of liver disease, no medical condition or medication associated with hepatic steatosis or fibrosis and normal metabolic profile were included in this cross-sectional analysis. Clinical data, anthropometry and blood samples were collected on the same day as transient elastography with controlled attenuation parameter was performed. RESULTS: 104 children (median age 12.8 years [IQR 11.4-14.8, range 7.9-17.7 years]; 59 [57%] boys) were included. Liver stiffness was positively correlated with age (Pearson's r = 0.39, p < 0.001). Median liver stiffness in boys (5.2 kPa [5th to 95th percentiles 3.6 to 6.8 kPa]) was greater than in girls (4.6 kPa [5th to 95th percentiles 3.6 to 6.1 kPa; p = 0.004]), but there was no difference by ethnicity. Median CAP was 179dB/m (5th to 95th percentiles 158 to 233dB/m). There was a positive correlation between CAP and body mass index (BMI) z-score, but no difference by age, sex, ethnicity or pubertal status. CONCLUSION: Liver stiffness values increase with age and are higher in healthy South African boys than girls, whereas CAP values vary with BMI, but not with age or sex.

Ready-to-use therapeutic foods for the treatment of malnourished children and infants.

PURPOSE OF REVIEW: Ready-to-use therapeutic foods (RUTF) allow effective community-based management of severe acute malnutrition (SAM). Current interest focuses on their optimal composition and use. RECENT FINDINGS: Studies of alternative RUTF have yielded differing results. Partial soybean, sorghum flour, and whey protein replacement RUTF were inferior to standard RUTF. In contrast, soy-based RUTF was as effective as milk-based RUTF and an alternative RUTF with added oats lead to superior recovery in comparison to standard RUTF.Reducing the dose of RUTF in the later phases of SAM recovery resulted in small reductions in the growth of uncertain clinical significance.Although iron and vitamin A status improve during treatment with standard RUTF, a significant proportion of children remained deficient. Alternative soya, maize, and sorghum-based formulas with no milk protein may improve recovery of iron status compared to standard RUTF.Finally, in children with SAM, plasma essential fatty acids and conversion to long-chain polyunsaturated fatty acids are reduced. Despite the improvement, these parameters remain lower than in normal children after 3 months. SUMMARY: New RUTF formulations may provide a cost-effective alternative to standard RUTF. Future research should focus on addressing micronutrient deficiency, lipid metabolism, and long-term recovery.

Viral hepatitis B and C in HIV-exposed South African infants.

BACKGROUND: Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa. METHODS: Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing. RESULTS: Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive. CONCLUSIONS: This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.

Ready-to-use therapeutic food (RUTF) for home-based nutritional rehabilitation of severe acute malnutrition in children from six months to five years of age.

BACKGROUND: Management of severe acute malnutrition (SAM) in children comprises two potential phases: stabilisation and rehabilitation. During the initial stabilisation phase, children receive treatment for dehydration, electrolyte imbalances, intercurrent infections and other complications. In the rehabilitation phase (applicable to children presenting with uncomplicated SAM or those with complicated SAM after complications have been resolved), catch-up growth is the main focus and the recommended energy and protein requirements are much higher. In-hospital rehabilitation of children with SAM is not always desirable or practical - especially in rural settings - and home-based care can offer a better solution. Ready-to-use therapeutic food (RUTF) is a widely used option for home-based rehabilitation, but the findings of our previous review were inconclusive. OBJECTIVES: To assess the effects of home-based RUTF used during the rehabilitation phase of SAM in children aged between six months and five years on recovery, relapse, mortality and rate of weight gain. SEARCH METHODS: We searched the following databases in October 2018: CENTRAL, MEDLINE, Embase, six other databases and three trials registers. We ran separate searches for cost-effectiveness studies, contacted researchers and healthcare professionals in the field, and checked bibliographies of included studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, where children aged between six months and five years with SAM were, during the rehabilitation phase, treated at home with RUTF compared to an alternative dietary approach, or with different regimens and formulations of RUTF compared to each other. We assessed recovery, deterioration or relapse and mortality as primary outcomes; and rate of weight gain, time to recovery, anthropometrical changes, cognitive development and function, adverse outcomes and acceptability as secondary outcomes. DATA COLLECTION AND ANALYSIS: We screened for eligible studies, extracted data and assessed risk of bias of those included, independently and in duplicate. Where data allowed, we performed a random-effects meta-analysis using Review Manager 5, and investigated substantial heterogeneity through subgroup and sensitivity analyses. For the main outcomes, we evaluated the quality of the evidence using GRADE, and presented results in a 'Summary of findings' table per comparison. MAIN RESULTS: We included 15 eligible studies (n = 7976; effective sample size = 6630), four of which were cluster trials. Eight studies were conducted in Malawi, four in India, and one apiece in Kenya, Zambia, and Cambodia. Six studies received funding or donations from industry whereas eight did not, and one study did not report the funding source.The overall risk of bias was high for six studies, unclear for three studies, and low for six studies. Among the 14 studies that contributed to meta-analyses, none (n = 5), some (n = 5) or all (n = 4) children were stabilised in hospital prior to commencement of the study. One small study included only children known to be HIV-infected, another study stratified the analysis for 'recovery' according to HIV status, while the remaining studies included HIV-uninfected or untested children. Across all studies, the intervention lasted between 8 and 16 weeks. Only five studies followed up children postintervention (maximum of six months), and generally reported on a limited number of outcomes.We found seven studies with 2261 children comparing home-based RUTF meeting the World Health Organization (WHO) recommendations for nutritional composition (referred to in this review as standard RUTF) with an alternative dietary approach (effective sample size = 1964). RUTF probably improves recovery (risk ratio (RR) 1.33; 95% confidence interval (CI) 1.16 to 1.54; 6 studies, 1852 children; moderate-quality evidence), and may increase the rate of weight gain slightly (mean difference (MD) 1.12 g/kg/day, 95% CI 0.27 to 1.96; 4 studies, 1450 children; low-quality evidence), but we do not know the effects on relapse (RR 0.55, 95% CI 0.30 to 1.01; 4 studies, 1505 children; very low-quality evidence) and mortality (RR 1.05, 95% CI 0.51 to 2.16; 4 studies, 1505 children; very low-quality evidence).Two quasi-randomised cluster trials compared standard, home-based RUTF meeting total daily nutritional requirements with a similar RUTF but given as a supplement to the usual diet (213 children; effective sample size = 210). Meta-analysis showed that standard RUTF meeting total daily nutritional requirements may improve recovery (RR 1.41, 95% CI 1.19 to 1.68; low-quality evidence) and reduce relapse (RR 0.11, 95% CI 0.01 to 0.85; low-quality evidence), but the effects are unknown for mortality (RR 1.36, 95% CI 0.46 to 4.04; very low-quality evidence) and rate of weight gain (MD 1.21 g/kg/day, 95% CI - 0.74 to 3.16; very low-quality evidence).Eight studies randomised 5502 children (effective sample size = 4456) and compared standard home-based RUTF with RUTFs of alternative formulations (e.g. using locally available ingredients, containing less or no milk powder, containing specific fatty acids, or with added pre- and probiotics). For recovery, it made little or no difference whether standard or alternative formulation RUTF was used (RR 1.03, 95% CI 0.99 to 1.08; 6 studies, 4188 children; high-quality evidence). Standard RUTF decreases relapse (RR 0.84, 95% CI 0.72 to 0.98; 6 studies, 4188 children; high-quality evidence). However, it probably makes little or no difference to mortality (RR 1.00, 95% CI 0.80 to 1.24; 7 studies, 4309 children; moderate-quality evidence) and may make little or no difference to the rate of weight gain (MD 0.11 g/kg/day, 95% CI -0.32 to 0.54; 6 studies, 3807 children; low-quality evidence) whether standard or alternative formulation RUTF is used. AUTHORS' CONCLUSIONS: Compared to alternative dietary approaches, standard RUTF probably improves recovery and may increase rate of weight gain slightly, but the effects on relapse and mortality are unknown. Standard RUTF meeting total daily nutritional requirements may improve recovery and relapse compared to a similar RUTF given as a supplement to the usual diet, but the effects on mortality and rate of weight gain are not clear. When comparing RUTFs with different formulations, the current evidence does not favour a particular formulation, except for relapse, which is reduced with standard RUTF. Well-designed, adequately powered, pragmatic RCTs with standardised outcome measures, stratified by HIV status, and that include diarrhoea as an outcome, are needed.

Severe acute malnutrition.

PURPOSE OF REVIEW: Advances in our understanding of the treatment of severe acute malnutrition (SAM) in a resource-limited environment are needed to improve outcome. RECENT FINDINGS: Ready-to-use therapeutic foods (RUTFs) made from local products and with reduced milk content lower costs and may be effective in older children. None of the therapeutic foods used to treat severely malnourished children correct long chain polyunsaturated fatty acid deficiencies.Routine short-term antibiotic (amoxicillin) treatment, in the context of adequate healthcare supervision, does not improve the recovery rate. Long-term antibiotic (cotrimoxazole) treatment also does not provide significant benefit to non-HIV-infected children.Increased pathogenic bacteria have been found in the intestinal microbiome of malnourished children and candidate organisms for use as probiotics have been identified. There is, however, no evidence to support the routine use of probiotics in these children. Although exocrine pancreatic function is reduced in malnourished children, routine pancreatic enzyme supplementation does not lead to accelerated recovery. SUMMARY: Alternative RUTF may provide a cheaper and more acceptable alternative to standard RUTF in the near future. Further research is needed to understand the implications of fatty acid deficiencies and dysbiosis that occur in malnourished children. Routine antibiotic administration in the appropriate setting is unnecessary.

Exome sequencing identifies a novel TTC37 mutation in the first reported case of Trichohepatoenteric syndrome (THE-S) in South Africa.

BACKGROUND: Trichohepatoenteric syndrome (THE-S) or phenotypic diarrhoea of infancy is a rare autosomal recessive disorder characterised by severe infantile diarrhoea, facial dysmorphism, immunodeficiency and woolly hair. It was first described in 1982 in two infants with intractable diarrhoea, liver cirrhosis and abnormal hair structure on microscopy. We report on two siblings from a consanguineous family of Somali descent who, despite extensive clinical investigation, remained undiagnosed until their demise. The index patient died of fulminant cytomegalovirus pneumonitis at 3 months of age. METHODS: Whole exome sequencing (WES) was performed on a premortem DNA sample from the index case. Variants in a homozygous recessive state or compound heterozygous state were prioritized as potential candidate variants using TAPER™. Sanger sequencing was done to genotype the parents, unaffected sibling and a deceased sibling for the variant of interest. RESULTS: Exome sequencing identified a novel homozygous mutation (c.4507C > T, rs200067423) in TTC37 which was confirmed by Sanger sequencing in the index case. The identification of this mutation led to the diagnosis of THE-S in the proband and the same homozygous variant was confirmed in a male sibling who died 4 years earlier with severe chronic diarrhoea of infancy. The unaffected parents and sister were heterozygous for the identified variant. CONCLUSIONS: WES permitted definitive genetic diagnosis despite an atypical presentation in the index case and suggests that severe infection, likely secondary to immunodeficiency, may be a presenting feature. In addition definitive molecular diagnosis allows for genetic counseling and future prenatal diagnosis, and demonstrates the value of WES for post-mortem diagnosis of disorders with a non-specific clinical presentation in which a Mendelian cause is suspected.

Composition of Follow-Up Formula for Young Children Aged 12-36 Months: Recommendations of an International Expert Group Coordinated by the Nutrition Association of Thailand and the Early Nutrition Academy.

BACKGROUND: There are no internationally agreed recommendations on compositional requirements of follow-up formula for young children (FUF-YC) aged 1-3 years. AIM: The aim of the study is to propose international compositional recommendations for FUF-YC. METHODS: Compositional recommendations for FUF-YC were devised by expert consensus based on a detailed literature review of nutrient intakes and unmet needs in children aged 12-36 months. RESULTS AND CONCLUSIONS: Problematic nutrients with often inadequate intakes are the vitamins A, D, B12, C and folate, calcium, iron, iodine and zinc. If used, FUF-YC should be fed along with an age-appropriate mixed diet, usually contributing 1-2 cups (200-400 ml) of FUF-YC daily (approximately 15% of total energy intake). Protein from cow's milk-based formula should provide 1.6-2.7 g/100 kcal. Fat content should be 4.4-6.0 g/100 kcal. Carbohydrate should contribute 9-14 g/100 kcal with >50% from lactose. If other sugars are added, they should not exceed 10% of total carbohydrates. Calcium should provide 200 mg/100 kcal. Other micronutrient contents/100 kcal should reach 15% of the World Health Organization/Food and Agriculture Organization recommended nutrient intake values. A guidance upper level that was 3-5 times of the minimum level was established. Countries may adapt compositional requirements, considering recommended nutrient intakes, habitual diets, nutritional status and existence of micronutrient programs to ensure adequacy while preventing excessive intakes.

Longitudinal controlled attenuation parameter and liver stiffness in children with and without perinatal HIV infection in South Africa.

OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging cause of liver disease in HIV. Transient elastography (TE) with controlled attenuation parameter (CAP) measures liver stiffness as a marker of liver fibrosis and CAP as a measure of hepatic steatosis. Our aim was to evaluate longitudinal CAP and liver stiffness in children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) from early life compared to HIV-uninfected children (HU). DESIGN: Prospective cohort study. METHODS: PHIV and HU were followed annually for two years. During the study, 60% of PHIV switched from older ART regimens to tenofovir disoproxil, lamivudine and dolutegravir (TLD). Longitudinal evolution of CAP and liver stiffness were investigated in two PHIV groups - on older ART and on TLD - compared to HU children using linear mixed effects models. RESULTS: 263 children and adolescents (112 PHIV, 151 HU) aged 7-20 years were followed. PHIV on older ART had CAP 8.61% (95% CI 4.42% to 12.97%, p < 0.001) greater than HU and no significant difference in CAP between PHIV on TLD and HU. No significant difference in liver stiffness was found between PHIV on older ART regimens and PHIV on TLD compared to HU. CONCLUSION: PHIV on older ART had higher CAP than HU, whereas in PHIV switched to TLD there was no difference in CAP compared to HU. There was no difference in liver stiffness between either PHIV group and HU. This suggests starting ART early in life might protect PHIV from developing hepatic fibrosis.

Ready-to-use therapeutic food for home-based treatment of severe acute malnutrition in children from six months to five years of age.

BACKGROUND: Malnourished children have a higher risk of death and illness. Treating severe acute malnourished children in hospitals is not always desirable or practical in rural settings, and home treatment may be better. Home treatment can be food prepared by the carer, such as flour porridge, or commercially manufactured food such as ready-to-use therapeutic food (RUTF). RUTF is made according to a standard, energy-rich composition defined by the World Health Organization (WHO). The benefits of RUTF include a low moisture content, long shelf life without needing refrigeration and that it requires no preparation. OBJECTIVES: To assess the effects of home-based RUTF on recovery, relapse and mortality in children with severe acute malnutrition. SEARCH METHODS: We searched the following electronic databases up to April 2013: Cochrane Central Register of Clinical Trials (CENTRAL), MEDLINE, MEDLINE In-process, EMBASE, CINAHL, Science Citation Index, African Index Medicus, LILACS, ZETOC and three trials registers. We also contacted researchers and clinicians in the field and handsearched bibliographies of included studies and relevant reviews. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials where children between six months and five years of age with severe acute malnutrition were treated at home with RUTF compared to a standard diet, or different regimens and formulations of RUTFs compared to each other. We assessed recovery, relapse and mortality as primary outcomes, and anthropometrical changes, time to recovery and adverse outcomes as secondary outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility using prespecified criteria, and three review authors independently extracted data and assessed trial risk of bias. MAIN RESULTS: We included four trials (three having a high risk of bias), all conducted in Malawi with the same contact author. One small trial included children infected with human immunodeficiency virus (HIV). We found the risk of bias to be high for the three quasi-randomised trials while the fourth trial had a low to moderate risk of bias. Because of the sparse data for HIV, we reported below the main results for all children together. RUTF meeting total daily requirements versus standard dietWhen comparing RUTF with standard diet (flour porridge), we found three quasi-randomised cluster trials (n = 599). RUTF may improve recovery slightly (risk ratio (RR) 1.32; 95% confidence interval (CI) 1.16 to 1.50; low quality evidence), but we do not know whether RUTF improves relapse, mortality or weight gain (very low quality evidence). RUTF supplement versus RUTF meeting total daily requirementsWhen comparing RUTF supplement with RUTF that meets total daily nutritional requirements, we found two quasi-randomised cluster trials (n = 210). For recovery, relapse, mortality and weight gain the quality of evidence was very low; therefore, the effects of RUTF are unknown. RUTF containing less milk powder versus standard RUTFWhen comparing a cheaper RUTF containing less milk powder (10%) versus standard RUTF (25% milk powder), we found one trial that randomised 1874 children. For recovery, there was probably little or no difference between the groups (RR 0.97; 95% CI 0.93 to 1.01; moderate quality evidence). RUTF containing less milk powder may lead to slightly more children relapsing (RR 1.33; 95% CI 1.03 to 1.72; low quality evidence) and to less weight gain (mean difference (MD) -0.5 g/kg/day; 95% CI -0.75 to -0.25; low-quality evidence) than standard RUTF. We do not know whether the cheaper RUTF improved mortality (very low quality evidence). AUTHORS' CONCLUSIONS: Given the limited evidence base currently available, it is not possible to reach definitive conclusions regarding differences in clinical outcomes in children with severe acute malnutrition who were given home-based ready-to-use therapeutic food (RUTF) compared to the standard diet, or who were treated with RUTF in different daily amounts or formulations. For this reason, either RUTF or flour porridge can be used to treat children at home depending on availability, affordability and practicality. Well-designed, adequately powered pragmatic randomised controlled trials of HIV-uninfected and HIV-infected children with severe acute malnutrition are needed.

Complementary Feeding in Western Cape, South Africa: Identifying Suboptimal Practices and Potential Targets for Intervention.

Introduction Appropriate complementary feeding is important for the normal growth and development of children. This study aimed to describe the complementary feeding practices and identify suboptimal practices that would be possible targets for intervention to improve practices among mothers of infants aged six weeks to one year in Western Cape Province, South Africa. Methods This hospital-based cross-sectional study was conducted at the emergency unit of the Department of Paediatrics and Child Health of Tygerberg Academic Hospital, Cape Town, South Africa, between May 2017 and June 2017 among 110 mothers and their infants. Infants with minor ailments were included in the study. Patients requiring hospital admissions or severely ill infants requiring oxygen or ventilation, premature babies, and children with congenital anomalies were excluded from the study. The relationship between sociodemographic variables and the time of commencement of complementary food was described. Results The mean age of infants was 6.4±3.2 months, while the mean age of mothers was 27.6±5.5 years. On average, the age at introduction of complementary food to infants was 2.17±1.50 months. Among the complementary foods given to infants less than six months of age, cereals were the most commonly introduced (76.5%), while the least were sweet beverages (5.9%). Maternal age ≤ 34 years and first-born infant were significantly associated with early commencement of complementary food before six months of age (p=0.042 and p=0.032, respectively). Conclusion This study indicated that commencement of complementary food as early as two months of age with the use of non-nutritious and inappropriate food remains a significant problem in the region. There is a need for further education of mothers on appropriate complementary feeding practices given the importance of complementary feeding practices to the optimum growth and development of children.

Settling in New Zealand's Small Towns: Experiences of Minority Ethnic Immigrants.

Small town New Zealand has, in recent years, experienced an increasing number1 and diversity of immigrants, with visible yet under-researched impacts for less populated regions that historically have been dominated by Pakeha (New Zealanders of European descent) and Maori populations. Using qualitative interviews with three ethnic sub-groups in the Clutha District and Southland Region-the Filipino, Samoan, and Malay communities-we investigate their experiences of settling in small towns. While there is considerable variation in the experiences and aspirations of these ethnic minorities, for each community we demonstrate how local and regional contextual factors shape life aspirations, support infrastructures and settlement trajectories. Particularly drawing upon informal networks and social capital immigrants mediate the considerable challenges they face. Our study also demonstrates the limitations of current policy support and initiatives. Indeed, while local authorities clearly have a significant role in creating the conditions for enabling immigrant settlement in small centres in Southland-Clutha, now the role of government services and community-based support also needs to be considered.

Decreased Hepatic Steatosis in South African Adolescents With Perinatal HIV Switching to Dolutegravir-containing Regimens.

BACKGROUND: Although dolutegravir (DTG) has a favorable metabolic profile, it has been linked to excess weight gain. We evaluated changes in hepatic steatosis in adolescents with perinatally acquired HIV switching to DTG-containing antiretroviral therapy (ART). METHODS: Virologically suppressed adolescents switched to dolutegravir for a minimum of 4 months or on unchanged ART (84% protease inhibitor) were assessed prospectively with anthropometry, transient elastography with controlled attenuation parameter (CAP) and fasting metabolic profiles. ART regimens were determined independently of the study. RESULTS: In total 68 adolescents [baseline median age 13.5 years [interquartile range (IQR): 12.5-14.4 years]; 42 (62%) female] were recruited. However, 38 remained on the same regimen and were followed for a median of 98 weeks (IQR: 48-108 weeks), and 30 switched to DTG and were followed for a median of 52 weeks (IQR: 49-101). There was no baseline difference in CAP between groups. There was no significant change in body mass index z-score in either group, but the median CAP in the DTG group decreased by -40dB/m (IQR: -51 to -31 dB/m) after a median of 44 weeks (IQR: 28-50 weeks) on DTG, compared to +1dB/m (IQR: -29 to +14 dB/m) in adolescents not switched ( P < 0 .01). Cholesterol and triglycerides were lower in those switched. Whereas hepatic steatosis prevalence decreased from 17% to 3% in adolescents who switched to dolutegravir, its prevalence doubled from 8% to 16% in those not switched ( P = 0.1). CONCLUSIONS: In this exploratory study, adolescents switched to DTG-containing regimens had reduced hepatic steatosis, cholesterol and triglycerides with no excess weight gain compared to those on unchanged ART.

Swallowing abnormalities in HIV infected children: an important cause of morbidity.

BACKGROUND: Swallowing disorders, well recognised in adults, contribute to HIV-infection morbidity. Little data however is available for HIV-infected children. The purpose of this study is to describe swallowing disorders in a group of HIV-infected children in Africa after the introduction of combined anti-retroviral therapy. METHODS: We describe 25 HIV-infected children referred for possible swallowing disorders. Clinical and videofluoroscopic assessment of swallowing (VFSS), HIV stage, and respiratory and neurological examination were recorded. RESULTS: Median age was 8 months (range 2.8-92) and 15 (60%) were male. Fifteen (60%) were referred for recurrent respiratory complaints, 4 (16%) for poor growth, 4 (16%) for poor feeding and 2 (8%) patients for respiratory complaints and either poor growth or feeding. Twenty patients (80%) had clinical evidence of swallowing abnormalities: 11 (44%) in the oral phase, 4 (16%) in the pharyngeal phase, and 5 (25%) in both the oral and pharyngeal phases. Thirteen patients had a videofluoroscopic assessment of which 6 (46%) where abnormal. Abnormalities were detected in the oral phase in 2, in the pharyngeal phase in 3, and in the oral and pharyngeal phase in 1; all of these patients also had evidence of respiratory involvement. Abnormal swallowing occurred in 85% of children with central nervous system disease. CNS disease was due to HIV encephalopathy (8) and miscellaneous central nervous system diseases (5). Three of 4 (75%) patients with thrush had an abnormal oral phase on assessment. No abnormalities of the oesophagus were found. CONCLUSIONS: This report highlights the importance of swallowing disorders in HIV infected children. Most patients have functional rather than structural or mucosal abnormalities. VFSS makes an important contribution to the diagnosis and management of these patients.

Prevalence and Risk Factors for Hepatic Steatosis in Children With Perinatal HIV on Early Antiretroviral Therapy Compared to HIV-Exposed Uninfected and HIV-Unexposed Children.

Objectives: We evaluated the prevalence and risk factors for hepatic steatosis in South African children with perinatally acquired HIV (PHIV) who started treatment early and remain on long-term antiretroviral therapy (ART) compared to HIV-uninfected children. Design: A cross-sectional study from April 2019 to October 2021. PHIV, HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled from an ongoing cohort study. Methods: All children had transient elastography (TE) with controlled attenuation parameter (CAP). Liver enzymes, lipogram, insulin and glucose were sent after an overnight fast. Multivariable linear regression analyses identified predictors of CAP. Hepatic steatosis was defined as CAP>248kPa. Results: 215 children (111 [52%] male; median age 14.1 years; IQR 12.7-14.9) participated in the study, 110 PHIV, 105 HIV-uninfected (36 HEU, 69 HU). PHIV initiated ART at a median age of 2.7 months (IQR 1.8-8.5). Hepatic steatosis prevalence was 9% in PHIV, 3% in HEU and 1% in HU children (p = 0.08). However, 8% of lean (body mass index z-score ≤ +1) PHIV had hepatic steatosis compared to zero lean HEU or HU children (p = 0.03). In multivariable linear regression analysis of all PHIV, body mass index (BMI) z-score was positively associated with CAP (p = 0.001) while CD4 count (p = 0.02) and duration of suppression of HIV viraemia (p = 0.009) were negatively associated with CAP, adjusting for age, sex and ethnicity. Conclusions: Hepatic steatosis prevalence was higher in lean PHIV than lean HIV-uninfected South African children. Longer suppression of HIV viraemia and higher CD4 count were associated with lower CAP and might be protective factors for hepatic steatosis in PHIV children.

A retrospective study of cryptosporidial diarrhea in a region with high HIV prevalence.

This retrospective study describes 63 patients <18 years of age presenting with cryptosporidial diarrhea to Tygerberg Children's' Hospital, a referral centre in the Western Cape, South Africa, from June 2004 through May 2005. Their mean age was 18.7 months (SD 17 months). Of the patients, 39 (62%) were male and 13 (20.6%) were HIV infected. Most children (57%) presented during the hot dry months of the year (December to March) and the majority (75%) of them required hospitalization. HIV-infected children were hospitalized for longer duration (median 18 days) than HIV-uninfected children (median 8.5 days). Four HIV-infected children (30.7%) died vs. four who were either HIV uninfected or of unknown status (p = 0.049). Seven of the children who died were malnourished. The CD4 count of HIV-infected children who died was 416 × 109) l⁻¹ compared with 1269 × 109 l⁻¹ (p = 0.1) for uninfected children. Cryptosporidium is an important cause of diarrhea among younger children in the Western Cape, which occurs more frequently during the dry months of the year and has a worse outcome in HIV-infected children.

Bilateral vocal fold palsy due to ingested battery in the postcricoid area/proximal esophagus.

Stridor is a common symptom associated with foreign body aspiration. In most cases, this is due to the foreign bodies lodging in the supraglottis, glottis, subglottis, or high extra-thoracic trachea. Infrequently, foreign bodies located in the esophagus cause stridor. The ingestion of button batteries (BBs) has been reported to cause multiple problems. The incidence has been estimated at 10.5 per million people per year with a case fatality rate of 0.5%. BBs predominantly cause esophageal mucosal injury. Mechanisms of injury include pressure necrosis, electrolysis, caustic exposure, or heavy metal toxicity. The reported complications include severe esophageal ulceration, trachea-esophageal fistula or aorto-esophageal fistula, and pneumonia. Vocal fold pathology after battery ingestion, other than edema of cords, has been rarely reported. We describe a case of acute bilateral vocal fold dysfunction and review the literature.

Abdominal Tuberculosis in Children: Challenges, Uncertainty, and Confusion.

The diagnosis of abdominal tuberculosis (TB) is challenging, and the prevalence of abdominal TB in children is likely underestimated. It may present with nonspecific abdominal symptoms and signs, but children who present with pulmonary TB may have additional abdominal subclinical involvement. Diagnosis is specifically challenging because none of the available diagnostic tools provide adequate sensitivity and specificity. In this review, we summarize the best available evidence on abdominal TB in children, covering the epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. We propose a diagnostic approach that could be followed for symptomatic children. We believe that a combination of investigations could be useful to both aid diagnosis and define the extent of the disease, and we propose that abdominal ultrasound should be used more frequently in children with possible TB and any abdominal symptoms. This neglected disease has received little attention to date, and further research is warranted.

Abdominal Involvement in Children With Bacteriologically Confirmed Tuberculosis: A Five-year Experience From Cape Town, South Africa.

BACKGROUND: Abdominal tuberculosis (TB) in children is poorly described and often poses a diagnostic challenge. We evaluated abdominal involvement in children presenting with bacteriologically confirmed TB. METHODS: We undertook a retrospective study at Tygerberg Hospital, Cape Town, from January 1, 2014, through December 31, 2018, of all children (<13 years) diagnosed with bacteriologically confirmed TB, in whom abdominal involvement was found. Demographic and clinical data were collected through folder review, laboratory records and imaging reports. RESULTS: Of 966 children with bacteriologically confirmed TB, 111 (11.5%) had abdominal involvement; 16 (14.4%) were excluded from further analysis because of lack of clinical data. The median age of the remaining 95 children was 43 months (interquartile range 20-94); 26 (27%) were HIV positive. The main gastrointestinal symptoms/signs were weight loss (84.2%), abdominal distention (54.7%), hepatomegaly (60.0%) and abdominal pain (26.3%). The main pathologic types were intra-abdominal lymph nodes (68.4%), solid organ involvement (54.7%), peritoneal type (23.2%) and intestinal type (10.5%). Splenic abscesses and solid organ involvement on ultrasonography were more common in HIV-positive children (P < 0.001 and P = 0.008, respectively). Liver abscesses were associated with age less than 5 years (P = 0.03), while abdominal lymphadenopathy on ultrasonography was more common in children older than 5 years (P = 0.038). Abdominal specimens were collected in an attempt to identify Mycobacterium tuberculosis in 15 of 95 (15.8%) patients and were positive in 13 of 15 (86.7%). CONCLUSIONS: Over 10% of children with confirmed TB had abdominal involvement. Abdominal TB should be considered in any pediatric TB case with abdominal symptoms, and ultrasonography should be the radiologic study of choice.

Hepatitis B virus drug resistance mutations in HIV/HBV co-infected children in Windhoek, Namibia.

In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected.