Research Articles (Paediatrics and Child Health)

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The association between micronutrient status and clinical outcomes in children with cancer undergoing treatment : a systematic review and meta-analysis
AbuSalameh, Hala; Li, Ruijie; de Oliveira, Nubia Maria; Schoeman, Judy; Huibers, Minke; van den Brink, Mirjam; Lovell, Amy L.; Rogers, Paul C.; Iniesta, Raquel Revuelta (Elsevier, 2026-06)
BACKGROUND & AIMS : Micronutrient abnormalities are common in children and young people (CYP) with cancer, yet their clinical implications remain unclear. This systematic review and meta-analysis examined the prevalence of micronutrient abnormalities and their associations with treatment complications and prognostic indicator outcomes in CYP undergoing cancer therapy. METHODS : We searched PubMed, EMBASE and Cochrane Library (inception–April 2025) for studies evaluating blood micronutrient status in CYP (0–21 years) with cancer. Primary outcomes were treatment-related toxicities; secondary outcomes were prognostic indicators outcomes including overall survival (OS) and event free survival (EFS). Two reviewers screened, extracted data and assessed risk of bias (JBI). Where ≥2 studies reported similar outcomes, random-effects meta-analyses pooled RRs, ORs or HRs with 95% CIs. RESULTS : Ten studies involving 1,229 CYP were included. Micronutrient abnormalities were frequent: folate deficiency ranged from 10 to 56%, selenium 20–58%, and zinc 30–70%, with several micronutrients declining during treatment. Lower folate showed the strongest association with toxicity, with significantly increased risks of febrile neutropenia (RR 2.22), neutropenia (RR 2.30), and thrombocytopenia (RR 2.80). Lower selenium was linked to poorer survival in individual studies and consistently associated with more treatment complications, although pooled EFS estimates were non statistically significant. Zinc, vitamin B12, and copper showed no significant pooled associations with EFS, and evidence for vitamins A, C, E, and magnesium was limited or inconsistent. CONCLUSIONS : Micronutrient abnormalities, particularly low folate, selenium, and zinc, are prevalent in CYP undergoing cancer treatment, with folate showing the most consistent associations with treatment complications. This supports the need for routine monitoring; however, large international multi-centre population-based and international mechanistic studies are warranted.
Mortality rate of infants with gastroschisis and healthcare-associated infections admitted in the neonatal and paediatric intensive care units in a tertiary hospital in Tshwane district, South Africa
Mbutho, M.M.T.; Coetzee, Melantha (Health and Medical Publishing, 2025-12)
BACKGROUND : Gastroschisis is associated with significant morbidity and mortality in neonates. Healthcare-associated infections (HAIs) worsen outcomes, with a high mortality, and timely management is crucial for survival. In South Africa, data regarding mortality and HAI management in neonates with gastroschisis are limited. OBJECTIVES. To evaluate the incidence of mortality and factors associated with mortality in neonates with gastroschisis admitted in the intensive care unit (ICU) and treated for HAI. METHODS : A retrospective study was conducted from July 2017 to October 2023. Eligible infants were identified using intensive care admission registers and the neonatal database. Patient demographics, treatment modalities, and outcomes, including mortality, were analysed. The Score for Neonatal Acute Physiology II (SNAP-II) severity was calculated retrospectively. RESULTS : A total of 66 neonates with gastroschisis and HAI that were admitted in the intensive care units were included in this study. Three neonates were managed for HAI twice, resulting in 69 HAI episodes. The incidence of culture-positive HAI was 77.9%, with a mortality of 84.8% per included neonate. Approximately half of the positive bacterial cultures with sensitivity testing were resistant to at least three classes of antimicrobial drugs. A SNAP-II score >30 was associated with higher mortality (p=0.038). Inotropic support was required in 76.8% of cases, correlating with higher mortality (p<0.001). CONCLUSION : HAI remains a major cause of mortality in neonates with gastroschisis. Higher SNAP-II scores and inotropic support were associated with poor outcome. The high incidence of multidrug-resistant pathogens highlights the need for tailored antimicrobial strategies. Further research is needed to improve survival rates in this high-risk populations.
Impact of the COVID‑19 pandemic on neonatal services and outcomes in a tertiary hospital in Tshwane, South Africa
Coetzee, Melantha; Tshehla, Rosine Marie; Naidoo, Harishia; Mulol, Helen; Feucht, Ute Dagmar (Health and Medical Publishing, 2025-12)
BACKGROUND : The COVID-19 pandemic's collateral damage has severely impacted global child health services. This study investigates its effects on neonatal services and outcomes at a tertiary hospital in Tshwane, South Africa. OBJECTIVE : The main aim was to assess if decreased breastfeeding, coupled with increased infant formula use owing to COVID-19-related visitation disruptions, was associated with higher incidences of healthcare-associated infections (HAI) and necrotising enterocolitis (NEC) in the hospital's neonatal unit. METHODS. As part of the Tshwane Maternal-Child COVID-19 study, we collected relevant data from three periods: pre-COVID-19, COVID-year-1 (COVID-Y1) and COVID-year-2 (COVID-Y2). RESULTS : Exclusive breastfeeding at discharge decreased from 72.9% pre-COVID-19 to 47.0% during COVID-19. Preterm formula purchases rose by 37.5% in COVID-Y1 and 25.0% in COVID-Y2, and term formula purchases increased by 77.8% in COVID-Y1. HAI incidence increased in both COVID-Y1 and COVID-Y2 compared with pre-COVID-19 (11.6% v. 8.1% and 12.0% v. 8.1%). NEC incidence significantly increased in COVID-Y2 for infants >1 500 g (1.8% v. 0.7%). CONCLUSION : This study underscores the indirect consequences of COVID-19 parental visitation restrictions, leading to infringements of breastfeeding rights and coinciding with increased HAI and NEC incidences in the hospital's neonatal unit.
Breastfeeding and antiretroviral access among HIV-exposed children during the peak COVID-19 pandemic lockdown in a rural district in South Africa
Mbira, T.E.; Prendergast, A.J.; Tylleskär, T.; Van de Perre, P.; Goga, Ameena Ebrahim; Ngandu, N.K. (Health and Medical Publishing, 2025-12)
BACKGROUND : There is limited information on whether the period of highest movement restrictions during the COVID-19 pandemic impacted on antiretroviral coverage for supporting safe breastfeeding among HIV-exposed children. OBJECTIVES : To (i) measure the prevalence of breastfeeding among HIV-exposed children during peak COVID-19 lockdown (March - June 2020); and (ii) explore its association with antiretroviral coverage and other factors. METHODS : A cross-sectional telephonic survey was conducted (September to November 2020), among women living with HIV (WLHIV) from rural Ehlanzeni District, South Africa (SA). Participants who were previously enrolled in a face-to-face study during 2019 and who provided consent for future studies, were invited to take part in the present survey. Data, including child feeding practices, were collected from maternal recall of the COVID-19 pandemic peak lockdown period. Descriptive statistics were calculated and factors associated with breastfeeding were analysed using log binomial regression. RESULTS : A total of 322 WLHIV aged between 19 and 46 years were successfully interviewed. Of these, only 6.4% reported disruption in antiretroviral treatment (ART), 18 (5.6%) had children living with HIV (CLHIV), all of whom were on ART. Out of the 300 HIV-exposed uninfected children (HEUs) who were eligible for extended postnatal prophylaxis (extended PNP) (those still breastfeeding, and the mother either had a viral load (VL) >1 000 copies/mL or had not undergone VL testing within the past 6 months), 47.7% received it. During the COVID-19 peak lockdown, 30.1% of children were breastfed, including 28.6% (n/N=87/304) of HEUs and 62.1% of breastfeeding HEUs were on extended PNP. Log binomial regression analysis showed HEUs on extended PNP and CLHIV had increased likelihood of breastfeeding (prevalence ratio (PR) 1.8 (95% confidence interval (CI) 1.2 - 2.6) and PR 2.6 (95% CI 1.6 - 4.4), compared with eligible HEUs who were not on extended PNP. CONCLUSION : Good antiretroviral coverage supported safe breastfeeding practices during the COVID-19 peak lockdown in this rural setting in SA, with promising ongoing adoption of extended PNP during breastfeeding.
A national survey of therapeutic facilities for managing hypoxic ischaemic encephalopathy in tertiary neonatal wards in South African public hospitals
Dhlomo, N.N.; Pepper, Michael Sean; Van Rensburg, Jeanne; Horn, A.R. (Health and Medical Publishing, 2025-12)
BACKGROUND : A 2011 South African (SA) survey noted substantial variability in provision of therapeutic hypothermia (TH) for moderate-severe neonatal encephalopathy due to suspected hypoxic-ischaemic encephalopathy (NESHIE). OBJECTIVES : To describe facilities, including TH, for babies with NESHIE in SA tertiary/specialised public hospitals. METHODS : A survey was emailed to representatives of all public tertiary/specialised hospitals with tertiary neonatal beds in SA. The survey contained questions regarding bed numbers, equipment, staffing, follow-up and barriers to the implementation of TH. RESULTS : Responses were received from all 25 hospitals across the nine provinces. Most hospitals (n/N=22/25; 88%) provided TH (median (range) per province: 2 (1 - 8)). The hospitals providing TH had more total neonatal beds (p=0.011) and more admissions with moderate-severe NESHIE (p=0.008) compared with those not providing TH. Most cooling centres (n/N=20/22; 91%) provided TH in their NICUs; six of these also cooled at lower levels of care. There was access to amplitude integrated electroencephalography (aEEG) and automated cooling in 91% of cooling centres. Manual cooling was used by 50% if automated TH was not available, 82% of which were validated methods. Late arrival was the most frequent barrier to provision of TH (80%). CONCLUSION : All provinces and most tertiary/specialised hospitals with tertiary neonatal beds in SA provided TH in 2023. The use of acceptable monitoring and cooling methods was widespread but insufficient, and some cooling methods in use were not validated. National registers and standardised protocols for patient selection and management are needed.
Haemoglobin levels and growth of South African infants aged 6–12 months exposed to maternal HIV infection
Tshiambara, Phumudzo; Hoffman, Marinel; Legodi, Heather; Mulol, Helen; Feucht, Ute Dagmar (Taylor and Francis, 2025-10-08)
INTRODUCTION : Anaemia is a significant public health concern in women of reproductive age and children under five years old,particularly in high HIV-prevalent settings. OBJECTIVE : This study analysed differences in haemoglobin levels and growth between human immunodeficiency virus (HIV)-exposed-but-uninfected (HEU) and HIV-unexposed-uninfected (HUU) infants, and further determined correlations between haemoglobin levels and growth at 6, 9, and 12 months in the Siyakhula study. RESULTS : At 6, 9, and 12 months postpartum, the maternal mean haemoglobin levels and anaemia status differed significantly by HIV status (p < 0.05), while HEU and HUU infants showed similar mean haemoglobin levels and anaemia status. Anaemia was prevalent in HEU infants at 6 (27%), 9 (33%), and 12 (30%) months. The HEU infants had lower weight-for-age Z-scores (WAZ)and mid-upper-arm circumference-for-age Z-scores (MUACZ) than HUU infants at 6, 9, and 12 months (p < 0.05). At 12 months, HEU infants had lower mean weight-for-length Z-scores (WLZ) than the HUU infants (-0.2 ± 1.2 vs. 0.2 ± 1.2; p = 0.020). The HEU infants had a higher prevalence of stunting at 6 months (16% vs. 8%; p = 0.044), and less breastfeeding at 9 (36% vs. 57%;p = 0.013) and 12 (25% vs. 48%; p = 0.005) months than the HUU infants. In HEU infants, positive correlations were found between infants’ haemoglobin levels and WAZ (p = 0.039), LAZ (p = 0.007), and MUACZ (p = 0.039) at 9 months, and with WAZ (p = 0.018) and WLZ (p = 0.017) at 12 months, while negative correlations were found between infant haemoglobin levels and any breastfeeding practices at 6, 9, and 12 months (p = 0.026; p < 0.001; p = 0.036). CONCLUSION : Maternal HIV infection can negatively impact infant growth, and anaemia remains a public health concern in South Africa.
Kinetics of anti-SARS-CoV-2 IgG in saliva and serum post infection, and subsequent vaccination in South Africa
Gededzha, Maemu P.; Sibiya, Mixo; Pellaton, Celine; Woeber, Kubashni; Nsibande, Duduzile; Mchunu, Nobuhle; Daniels, Brodie; Chetty, Terusha; Dassaye, Reshmi; Mohlabi, Khanya; Jaumdally, Shameem; Dheda, Keertan; Lekalakala, Ruth; Madhi, Shabir A.; Mayne, Elizabeth; Gray, Glenda; Levy, Yves; Fenwick, Craig; Ding, Song; Moore, Penny L.; Goga, Ameena Ebrahim (AOSIS, 2026-06-26)
BACKGROUND : Understanding mucosal immune response to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, and its correlation to systemic responses could improve vaccine development. There is limited data on mucosal and systemic antibody responses to SARS-CoV-2 infection and vaccination in African populations. Objective: This study assessed serum and saliva antibody ratios in a cohort of SARS-CoV-2 infected and vaccinated participants followed up for 12 months. METHODS : This longitudinal study comprised of 67 SARS-CoV-2, PCR-confirmed participants who were recruited as part of a COVID-19 Point of Care Study, between January 2021 and September 2022. For this analysis, 254 serum and 214 saliva samples (205 of which were matched), were collected at baseline, 6, 9, and 12 months. Antibodies against Spike (S) and nucleocapsid (N) SARS-CoV-2 were assessed by in-house Luminex assay. RESULTS : Serum and saliva anti-S IgG from were detected for up to 12 months in majority of participants (93.5% and 90%), regardless of vaccination status. There was a concordance between paired serum and saliva antibody in 80.5% anti-S IgG and 41.7% anti-N IgG of samples. There was a weak but significant correlation between the matched serum and saliva samples (ρ = 0.42, p < 0.001 for anti-S and ρ = 0.33, p < 0.001 for anti-N). Longitudinal analysis in participants who were vaccinated with either the Ad26.COV2 or BNT162b2 COVID-19 vaccine after their baseline visit, serum anti-S IgG significantly increased (p = 0.023 and p = 0.038), compared with unvaccinated participants. Breakthrough infections or reinfections were identified in (35/62) 56.5% of vaccinated and unvaccinated participants. CONCLUSION : This study reports the correlation of the anti-S and anti-N IgG responses in serum and saliva following SARS-CoV-2 infection and subsequent vaccination in low-middle income setting. Furthermore, high breakthroughs and reinfection were reported. WHAT THIS STUDY ADDS : The study findings are consistent with those from high-income settings, supporting correlation between systemic and mucosal immunity and booster vaccination as a long-term strategy to control SARS-CoV-2.
Real-world effectiveness of Ad26.COV2.S or BNT162b2 booster vaccines against severe COVID-19 in adults who received a primary dose of Ad26.COV2.S in South Africa during the Delta period : a retrospective cohort study using medical scheme data
Fairall, L.; Yende-Zuma, N.; Reddy, T.; Garrett, N.; Goga, Ameena Ebrahim; Bennett, Sarah; Folb, N.; Seocharan, I.; Mametja, S.; Semenya, M; Simelane, S.R.N.; Bekker, L.-G.; Gray, G.E. (South African Medical Association, 2025-08)
BACKGROUND. From March 2020 to June 2022, South Africa (SA) confronted successive waves of COVID‑19, each linked to emerging SARS-CoV-2 variants. Vaccines played a critical role in preventing severe disease and death, but as new SARS-CoV-2 variants emerged, with increasing breakthrough infections, questions arose about the real-world effectiveness of first-generation vaccines containing the ancestral strain against evolving variants including Delta and Omicron BA.1 and BA.4/5 SARS-CoV-2. OBJECTIONS. To assess the real-world effectiveness of ancestral strain booster doses (either Ad26.COV2.S or BNT162b2) in preventing severe COVID‑19 outcomes, including hospitalisation, admission to critical care and death, among essential workers in SA who received a primary dose of Ad26.COV2.S against emerging SARS-CoV-2 variants. METHODS. A retrospective cohort study was conducted using data from a large private health insurance scheme. Individuals who received a single dose of Ad26.COV2.S as their primary vaccination were included. Time-varying Cox regression models were used to assess the effectiveness of boosting with either Ad26.COV2.S or BNT162b2 v. not boosting against severe COVID‑19 outcomes associated with emerging variants, adjusting for various demographic and clinical factors. RESULTS. By August 2021, a total of 407 961 individuals received a first dose of Ad26.COV2.S, of whom 350 688 were eligible for and 332 286 included in the vaccine effectiveness (VE) analysis. Of these, 206 359 (62%) received no further doses, while 113 957 (34%) received a second dose of Ad26.COV2.S and 11 970 (4%) received a second dose of BNT162b2 by August 2022. During the follow-up period (November 2021 - August 2022), 1 125 COVID‑19-related hospital admissions, 198 admissions to critical care and 41 COVID‑19-related deaths were recorded. Adjusted relative VE against severe outcomes was 34% (95% confidence interval (CI) 19 - 45) for hospital admission, 51% (95% CI 22 - 70) for critical care admission, and 89% (95% CI 13 - 98) for COVID‑19-related death. CONCLUSION. While most participants remained unboosted, administration of either ancestral strain Ad26.COV2.S or BNT162b2 vaccination provided protection against severe COVID‑19 outcomes among essential workers in SA during the dominance of the Omicron BA.1 and BA.4/5 variants, demonstrating cross-strain protection.
Risk factors for developing intraventricular haemorrhage in very low-birthweight infants at Kalafong Provincial Tertiary Hospital, South Africa, 2019-2020
Mahlako-Lekalakala, Kgahliso; Paulse, Natalie (South African Medical Association, 2026-03-04)
BACKGROUND : Intraventricular haemorrhage (IVH) remains a major concern as a result of the high prevalence of preterm births globally. OBJECTIVES : To identify maternal and neonatal risk factors associated with IVH, and to assess its incidence and most frequently occurring grade in a population of very low-birthweight infants (VLBWIs) at Kalafong Provincial Tertiary Hospital, South Africa (SA). METHODS : This retrospective cohort study included all infants of birthweight <1 500 g admitted between 1 January 2019 and 31 December 2020. Associations between IVH and maternal and neonatal risk factors were analysed using Pearson’s χ2 test and Fisher’s exact test. Risk factors significantly associated with IVH were included in a binary logistic regression model to identify independent predictors. Risk factors significantly associated with IVH (p<0.05) corresponded to a 95% confidence level. RESULTS : IVH was diagnosed during the first week of life in 43 out of 127 VLBWIs who met the inclusion criteria. Hypoglycaemia remained the most significant independent risk factor after adjusting for potential confounders in the multivariable logistic regression: adjusted odds ratio 4.02 (95% confidence interval (CI) 1.52 - 10.64). The incidence of IVH was 33.9% (95% CI 25.7 - 42.1). Grade I IVH occurred in 83.7% of infants, grade II in 9.3% and grades III - IV in 7.0%. CONCLUSION : This study found an association between hypoglycaemia and IVH, but causality could not be established owing to the nature of the study. In this tertiary hospital in SA, a third of VLBWIs had IVH, mostly graded as mild.
Growth assessment of children and adolescents with type 1 diabetes mellitus at Steve Biko Academic Hospital in Pretoria, South Africa : a cross-sectional study of factors contributing to stunting
Badenhorst, C.J.; Rheeder, Paul; Karsas, Maria (South African Medical Association, 2026-03)
BACKGROUND : The continuous rise in the prevalence of type 1 diabetes mellitus (T1DM) places pressure on countries to increase the resources needed to manage patients adequately. Studies have documented an association socioeconomic status between poor glycaemic control and stunting, which poses a significant health concern. Minimal data are available on the prevalence of stunting in T1DM in South Africa. OBJECTIVE : To establish the prevalence of stunting in a population of paediatric T1DM patients and determine contributing factors. METHODS : A descriptive, cross-sectional study was conducted at the Paediatric Diabetes Clinic of the Steve Biko Academic Hospital, Pretoria. Data were collected from patient files, a questionnaire and the National Health Laboratory Service database. Stunting was defined as height-for-age Z-score (HAZ)<–2. RESULTS : Of the 169 recruited patients, 115 were included (56.5% female). The prevalence of stunting was 10.4%. The median haemoglobin A1c (HbA1c) was 11.8%. Stunting was significantly associated with poor glycaemic control (p=0.008), older age (p=0.039), presence of comorbidities (p=0.026), underweight (p=<0.001) and food insecurity (p=0.021). Genetic factors were also associated with stunting, specifically lower paternal height (p=0.006) and decreased mid-parental height Z-score (p=0.035). CONCLUSION : Stunting in children and adolescents with T1DM was associated with poor glycaemic control, nutritional and socioeconomic factors, comorbidities, older age and genetic factors. The results point to a multifactorial contribution to impaired growth. To promote growth in children with T1DM, a multidisciplinary approach is essential, with a focus on optimising glycaemic control, addressing nutritional status and food insecurity, managing comorbidities and monitoring growth against genetic potential regularly.
First-year growth patterns of preterm infants receiving kangaroo mother care : associations with early life factors and 1-year anthropometry
Nel, Sanja; Feucht, Ute Dagma; Botha, Tanita; Arashi, Mohammad; Wenhold, Friedeburg Anna Maria (Springer, 2025-10-15)
BACKGROUND : This study characterises first-year growth patterns in a historical preterm infant cohort, and investigates associated early-life factors and 1-year anthropometry. METHODS : We analysed 322 South African preterm infants’ (mean 32.8 ± 2.4 weeks gestation) 1-year clinic records after kangaroo mother care discharge. Latent class trajectory modelling identified patterns of weight-for-age (WAZ), length-for-age (LAZ), weightfor-length (WLZ), and head circumference-for-age (HCZ) z-scores (Fenton 2013 Growth Chart; WHO Growth Standards, agecorrected). Z-score patterns were characterised as maintenance, faltering (progressively decreasing), gain (progressively increasing) or catch-up (rapidly increasing, exceeding birth z-score). Ordinal regression analysis investigated associations of early-life maternal/infant factors, birth weight, and early (until 50 weeks postmenstrual age) WAZ gain with growth patterns. One-year stunting (LAZ < -2), wasting (WLZ < -2) and overweight (body mass index-for-age z-score > +2) were compared. RESULTS : Best-fit models identified three WAZ and LAZ patterns (gradual gain, faltering, catch-up), three WLZ patterns (maintenance, faltering, catch-up) and two HCZ patterns (maintenance, gain). Most infants displayed maintenance, gradual gain or catch-up. Lower birth weight z-score (BWZ) was associated with LAZ catch-up (OR:8.33 (3.13–20.00)), WLZ faltering (OR:2.94 (1.69–5.00)) HCZ gain (OR:1.92 (1.23–3.13)), but lower odds of gradual WAZ gain (OR:0.36 (0.19–0.68)) and WAZ faltering (OR:0.56 (0.34–0.92)). Smaller early WAZ gains were associated with gradual WAZ gain (OR:2.27 (1.56–3.33)), WAZ faltering (OR:1.47 (1.11,1.96)), LAZ catch-up (OR:1.85 (1.25–2.70)), and LAZ faltering (OR:1.39 (1.09–1.75)). WAZ and WLZ faltering were both associated (p < 0.001) with 1-year stunting (45.5%, 23.5%) and wasting (21.8%, 10.3%). CONCLUSIONS : Most preterm infants had appropriate first-year growth. Lower BWZ was associated with WAZ and LAZ catch-up but WLZ faltering, and sub-optimal early WAZ growth with growth faltering.
The effects of in utero HIV and antiretroviral therapy exposure on infant T-cell and monocyte activation, function, and regulation of immune-modulatory pathways
Prinsloo, Andrea; Steel, Helen Carolyn; Feucht, Ute Dagmar; Rossouw, Theresa M. (Wiley, 2026-03)
Human immunodeficiency virus (HIV) infection is characterized by chronic, systemic immune activation. It is unclear how this affects the immune system of infants born to mothers living with HIV (MLWH). The current study assessed whether maternal HIV status and in utero antiretroviral therapy (ART) exposure impact infant T-cell and monocyte activation and regulation, as well as monocyte responsiveness to stimulation at birth and early infancy. T-cell and monocyte activation and expression of immune checkpoint molecules were characterized by means of flow cytometry. Pro- and anti-inflammatory cytokine/chemokine profiles were assessed using a suspension bead array assay. Seventy-one pregnant MLWH and 77 mothers not living with HIV (MNLWH) were recruited at 22 weeks’ gestation, and mother-infant pairs were followed until 6 months postpartum. MLWH had higher percentages of CD4+ and CD8+ T-cells expressing programmed cell death protein-1 (PD-1) and a higher percentage of regulatory T-cells (Tregs). HIV-exposed-but-uninfected (HEU) infants displayed disrupted CD4+ T-cell maturation with an increased number of CD8+ T-cells expressing PD-1 at the time of birth and increased T-cell exhaustion at 10 weeks of age. Higher levels of monocyte activation were observed in MLWH with increased numbers of classical (CL) monocytes expressing CCR2 and CD80. An increased percentage of CL monocytes expressing CCR2 and CD80 was noted in HEU infants at the time of birth, which persisted at 10 weeks of age. Significantly higher levels of C-reactive protein (CRP) and non-significantly higher levels of interleukin (IL)-6 and tumor necrosis factor-alpha were observed in MLWH, indicative of hyperactivated innate inflammation. HEU infants had persistently increased levels of IL-8 and transforming growth factor (TGF)-β1, and lower levels of IL-10, IFN-γ, and CRP. The latter might be secondary to cotrimoxazole use in the HEU infants while the altered cytokine levels might be indicative of altered immune programing. In summary, this cohort study showed that maternal HIV status has a transient effect on basal infant T-cell and monocyte activation, regulation, and monocyte responsiveness, which dissipates at 6 months of age, while altered cytokine levels persisted.
Mitochondrial DNA disorders in neuromuscular diseases in diverse populations
Gao, Fei; Schon, Katherine R.; Vandrovcova, Jana; Koken, Ozlem Yayıcı; Raga, Sharika; Naidu, Kireshnee; Schoonen, Maryke; Rani, Nimita; Tomaselli, Pedro; Baskar, Dipti; Kapapa, Musambo; Polat, Ipek; Wilson, Lindsay A.; Thangaraj, Kumarasamy; Yis, Uluc; Nandeesh, Bevinahalli N.; Bearden, David; Kvalsund, Michelle; Henning, Franclo; Vengalil, Seena; Nalini, Atchayaram; Sobreira, Claudia F.R.; Marques, Wilson; Topologlu, Haluk; Hanna, Michael G.; Yareeda, Sireesha; Vishnu, Venugopalan Y.; Van der Westhuizen, Francois H.; Smuts, Izelle; Meldau, Surita; Wilmshurst, Jo; Cavdarlı, Busranur; Heckmann, Jeannine; Chinnery, Patrick F.; Horvath, Rita (Wiley, 2025-08)
Neuromuscular features are common in mitochondrial DNA (mtDNA) disorders. The genetic architecture of mtDNA disorders in diverse populations is poorly understood. We analysed mtDNA variants from whole-exome sequencing data in neuromuscular patients from South Africa, Brazil, India, Turkey and Zambia. In 998 individuals, there were two definite diagnoses, two possible diagnoses and eight secondary findings. Surprisingly, common pathogenic mtDNA variants found in people of European ancestry were very rare. Whole-exome or -genome sequencing from undiagnosed patients with neuromuscular symptoms should be re-analysed for mtDNA variants, but the landscape of pathogenic mtDNA variants differs around the world.
Validating self-reported exclusive breastfeeding in Eswatini using stable isotope techniques
Simelane, Kwanele Siyabonga; Mhlanga, Tholakele; Mkhaliphi, Nhlakanipho Sandziso; Zwane, Siniketiwe; Dlamini, Glorious; Gadaga, Henry; Mulol, Helen; Coutsoudis, Anna (Public Library of Science, 2026-04-15)
Exclusive breastfeeding (EBF) prevalence at the population level is typically assessed through maternal or caregiver reports, which are prone to recall and social desirability biases. The deuterium oxide dose-to-mother (DTM) technique offers an objective alternative by administering a small amount of deuterium-labeled water to lactating mothers. This study compared the prevalence of EBF from maternal recall versus the DTM method in Eswatini and evaluated the strengths and limitations of both approaches in assessing infant feeding practices linked to malnutrition. A total of 102 mother-infant pairs were recruited from three regional hospitals and three health centers in Eswatini. EBF was assessed by maternal recall using the WHO 24-hour infant feeding recall method and objectively measured using the DTM stable isotope technique at three infant age intervals: 6 weeks to 2.4 months (n = 26), 2.5 to 4.0 months (n = 43), and 4.1 to 5.5 months (n = 33). Two cutoff values defined EBF status via the stable isotope method. Agreement between maternal recall and DTM measurements was analyzed using Kappa statistics. Maternal recall consistently overestimated EBF across all time points compared to the DTM method. Using Model 1 cutoffs, prevalences of EBF by maternal recall vs. DTM were 100% vs. 50% (≤2.4 months), 79.5% vs. 18.2% (2.5–4 months), and 71.9% vs. 18.8% (4.1–5.5 months). For Model 2, prevalences were 100% vs. 65.4%, 79.5% vs. 50%, and 71.9% vs. 43.8%, respectively. The difference between the two models is the cutoff that was used to determine EBF using the DTM method. Kappa analysis showed minimal agreement between methods at each time point. The DTM technique provides a more accurate and objective measure of EBF than maternal recall and is the gold standard for smaller sample studies. Maternal recall substantially overestimated exclusive breastfeeding prevalence, while the deuterium oxide technique yielded more reliable, objective assessments of infant feeding practices, highlighting the need to interpret recall data with caution due to overreporting.
Establish global nutrition research strategies: the meeting report of the First SIOP Nutrition Research Forum
Gala, Rajul M.; Schoeman, Judy; Iniesta, Raquel Revuelta; Van den Brink, Mirjam; Lovell, Amy L.; Huibers, Minke H.W. (MDPI, 2026-03)
Despite strong evidence linking nutritional status to treatment efficacy and survival in pediatric cancer, significant knowledge gaps and practice variation persist globally. On 24th October 2025, the International Society of Paediatric Oncology (SIOP) Nutrition Network, in collaboration with Prinsess Máxima Center for Paediatric Oncology and the International Initiative for Pediatrics and Nutrition (IIPAN), convened the first global SIOP Nutrition Network Research Forum. The forum brought together 54 international experts from high-income countries and low- and middle-income countries to define global nutrition research strategies for pediatric oncology. The forum addressed six emerging domains: body composition and treatment outcomes; microbiome, micronutrient status and metabolic health; prehabilitation and rehabilitation strategies; validation of nutritional assessment tools, guideline development for high-income settings; insights from international multicentric research initiatives—the International Atomic Energy Agency (IAEA), SIOP Nutrition Network, the Adapted Resource and Implementation Application (ARIA) guide nutrition portal, the International Collaboration on Nutrition in Cancer (ICONIC) WHO knowledge portal; and IIPAN and the World Cancer Research Fund (WCRF) for funding strategies. Delegates identified three priority working groups, namely prehabilitation optimization, pharmacokinetics, and advocacy, with each outlining collaborative nutrition research priorities for the next five years. This forum represents a critical point in pediatric oncology nutrition research as it established the first coordinated and internationally endorsed roadmap to bridge gaps in cancer care and ensure standard nutrition care worldwide. The research priorities and collaborations will help in creating evidence to improve cancer treatment and survival rate for children globally.
Severe, primary, and incidental COVID-19 in hospitalised children, South Africa : 2020-2023
Goga, Ameena Ebrahim; Ramraj, Trisha; Cloete, Jeane; Mawela, Dini; Waggie, Zainab; Archary, Moherndran; Chinniah, Kogielambal; Jeena, Prakash; Tabane, Nomakhuwa E.; Van Zyl, Riana; Reubenson, Gary; Strehlau, Renate; Feucht, Ute Dagmar; Reddy, Tarylee; Mchunu, Nobuhle; Cawood, Shannon; Zuhlke, Liesl; Webb, Kate; Zar, Heather J.; Donald, Kirsten A.; Scott, Christiaan; Morrow, Brenda M.; Aldersley, Thomas; Du Plessis, Nicolette Marie; Chetty, Terusha; Velaphi, Sithembiso; Dangor, Ziyaad; Moore, David P. (International Society of Global Health, 2026-01-30)
BACKGROUND : Knowledge gaps persist regarding paediatric COVID-19 clinical presentation, treatment and outcomes in high HIV prevalence settings, with low COVID-19 vaccine coverage. METHODS : An ambi-directional cohort study was conducted in 13 South African public sector hospitals. Hospitalised children with SARS-CoV-2 infection or post-infection syndrome were included. Main outcomes measures included severe disease and primary COVID-19 (hospitalisation for SARS-CoV-2 infection). RESULTS : There were 2363 SARS-CoV-2 positive children included (March 2020 through May 2023); median age 23.6 months (interquartile range (IQR) = 4.3–98.2 months). Excluding missing values, 1618 (68.9%) children had primary COVID-19; 1121 (69.3%) of these had severe primary COVID-19. In the primary COVID-19 group with data, 318 / 1588 (20.0%) received intensive or high care, 121/1285 (9.4%) received a blood transfusion and 48/1616 (3.0%) died. Multivariable analyses demonstrated that severe primary COVID-19 was 32% higher in children aged 29–365 days (adjusted Risk Ratio (aRR) = 1.32 (95% confidence interval (CI) = 1.13–1.55); reference: 0–28 days), 13% higher with one or more comorbidities (aRR = 1.13; CI = 1.05-1.22)), and 14–22% lower during the Beta, Delta and Omicron periods (reference: ancestral period). Amongst all hospitalised children with a positive SARS-CoV-2 test, severe disease was commoner in underweight children (aRR 1.09; CI = 1.02–1.17, P = 0.013)). Severe signs were commoner in children living with HIV (CLHIV), 88/121 (72.7%), vs. HIV uninfected 1320 / 2104 (62.7%), P = 0.026, and in antiretroviral therapy-naïve CLHIV, (37 / 41 (90.2%), vs. CLHIV on therapy 51 / 80 (63.8%), P = 0.002). CONCLUSIONS : In a high HIV prevalence country, approximately 70% of children with a positive SARS-CoV-2 test were hospitalised for COVID-19 treatment; almost 70% of these children were severely ill. Controlling for other factors, disease severity was highest in the hypothesised pre-immunity Ancestral period. HIV infection and delayed ART initiation were associated with severe signs. In such settings, strengthening general child health programmes to reduce underweight and prevent or treat paediatric HIV may reduce the severity of new diseases of pandemic proportion.
Xanthogranulomatous pyelonephritis in a child with autoimmune joint disease
Kriek, Pieter Willem; Karsas, Maria; Cloete, Jeane (Springer, 2025-11-06)
Xanthogranulomatous pyelonephritis is a rare condition in paediatric patients, mostly described in middle-aged female patients. We present a 7-year-old female with juvenile idiopathic arthritis, who was found to have a kidney mass with a concurrent Escherichia coli urinary tract infection. Surgical excision was done out of concern for possible malignancy. Histology confirmed the diagnosis of xanthogranulomatous pyelonephritis and persistent E. coli infection.
Management outcomes of South African children diagnosed with neuroblastoma in adolescence
Van Heerden, Jaques; Esterhuizen, Tonya; Du Plessis, Jan; Geel, Jennifer; Buchner, Ane; Van Zyl, Anel; Hendricks, Marc; Naidu, Gita; Van Emmenes, Barry; Vaithilingum, M.; Kruger, Mariana (Elsevier, 2025-03)
BACKGROUND : Neuroblastoma (NB) is an indolent disease in adolescents. Only 5 % of neuroblastoma diagnoses are made in adolescents and adults. Limited data exists on Africans of older age groups. OBJECTIVES : We aimed to compare the characteristics and outcomes of South African children ≥10 years diagnosed with NB with international reports. PATIENTS AND METHODS : Multicentric, retrospective data of South African patients (0–15 y) with NB diagnosed between January 2000 and December 2016 were analyzed. Clinical profiles and outcomes of adolescents (≥10 years) with NB were compared to those of the younger patients in our cohort. The outcomes of adolescents (≥10 years) with NB were compared with those reported in the global literature. RESULTS : Thirty adolescents with a male-to-female ratio of 1:0.6 were diagnosed with NB, constituting 6.5 % of all patients with NB. Metastatic disease at diagnosis was present in 24 (75 %), including lung metastases in 2 (6 %). Half of the patients presented with a raised lactate dehydrogenase (LDH) and/or ferritin and unfavorable pathology. Post-induction remission rates were higher in the adolescent group (33 %) compared to the 18–59 months (24.8 %) and 5–9.9 years (29.7 %) cohorts but less than the <18 months (47.2 %) cohort (p < 0.001). The adolescent group had the poorest five-year overall survival (20.9 %) compared to the children <18 months (39.0 %), 18–59 months (44.1 %), or 5–9.9 years old (63.5 %) (p < 0.001). CONCLUSIONS : Despite a favorable response rate to induction chemotherapy, the five-year overall survival of adolescents with NB is dismal in South Africa.
Population impact of South Africa's human papillomavirus (HPV) vaccination programme on HPV prevalence in adolescent girls with and without HIV : a repeat cross-sectional study
Machalek, Dorothy A.; Nyemba, Dorothy C.; Travill, Danielle; Petoumenos, Kathy; Mbulawa, Zizipho Z.A.; Naidoo, Ishana; Motshwane, Feni M.M.; Bamford, Lesley; Rees, Helen; Kaldor, John M.; Delany-Moretlwe, Sinead (Elsevier, 2026-04)
BACKGROUND : A school-based human papillomavirus (HPV) vaccination programme providing protection against types 16 and 18 of HPV was introduced in South Africa in 2014 for Grade 4 girls (aged ≥9 years), achieving 87% coverage among learners with at least one of the two recommended doses. We evaluated the programme's impact on HPV prevalence among adolescent girls in a setting of high HIV prevalence. METHODS : In this repeat cross-sectional study, girls aged 17–18 years were invited from 15 primary health-care clinics in four provinces (Free State, Gauteng, Mpumalanga, and North West) of South Africa to provide a self-collected vaginal sample for HPV testing (AnyPlex II HPV28, Seegene, Seoul, South Korea). A survey done from June 19 to Dec 11, 2019, estimated baseline (pre-vaccine) HPV prevalence. A repeat survey done from Feb 16 to Dec 6, 2023, estimated HPV prevalence in a group eligible for the vaccination programme (post-vaccine). Vaccination status was assessed through district registers and self-reported data. The primary outcome was the impact of the HPV vaccination programme, measured as the relative reduction in HPV prevalence between the two birth cohorts using generalised linear regression (estimating adjusted prevalence ratios), overall and by HIV status. FINDINGS : Of 2470 participants enrolled, 819 girls were recruited for the pre-vaccine survey (248 living with HIV) and 1538 for the post-vaccine survey (295 living with HIV). Prevalence of HPV vaccine types HPV-16 and HPV-18 declined by 83%, from 21·6% (177 of 819 participants) in the pre-vaccine group to 3·2% (49 of 1538 participants) in the post-vaccine group (adjusted prevalence ratio 0·17, 95% CI 0·12–0·24; p<0·0001). A similar reduction was observed among those living with HIV, with prevalence decreasing from 29·4% (73 of 248 participants) in the pre-vaccine group to 4·4% (13 of 295 participants) in the post-vaccine group (adjusted prevalence ratio 0·18, 95% CI 0·10–0·32; p<0·0001). No significant reductions were noted for other HPV types, except HPV-31 and HPV-45, which is consistent with cross-protection. INTERPRETATION : In this large-scale evaluation of South Africa's two-dose HPV vaccination programme, we observed impacts similar to those seen with three-dose programmes in high-income settings, including equivalent impacts among adolescent girls living with HIV. These findings underscore the substantial population-level benefits of high-coverage routine HPV vaccination in a high-HIV-burden setting.
Characterization of early viral populations in infants acquiring HIV through perinatal and breastmilk transmission : a review of what is currently known and the gaps that need to be addressed to guide passive HIV immunization of breastfeeding infants
Giorgi, Elena E.; Abrahams, Melissa-Rose; Fouda, Genevieve; John-Stewart, Grace; Goga, Ameena Ebrahim; Mullins, James I.; Permar, Sallie R.; Janes, Holly; Martin, Troy M. (Bentham Science Publishers, 2025-09)
Newborns represent only 1% of the population. Yet, HIV vertical transmissions represent 10% of all new infections globally, even though antiretroviral therapy (ART) has been shown to reduce the risk of vertical transmission to less than 2%. While vaccines still represent the most efficient and cost-effective intervention to eradicate new infections, HIV immunogens that can effectively elicit broad-spectrum protection are still at least a decade away. In contrast, passive immunization with broadly neutralizing antibody (bnAb) combinations has the potential to provide a more immediate pathway to HIV prophylaxis. Early-phase infant trials are underway to establish the safety and pharmacokinetics of bnAb combinations selected for their potency against viruses acquired via adult transmissions. However, the specific characteristics and phenotypic differences of vertically transmitted viruses in infants compared to those in adults remain uncertain, including their susceptibility to known broadly neutralizing antibodies (bnAbs). We review the current knowledge of vertically transmitted HIV viruses, including their genetics and phenotypic features. Differences in immunity between adults and infants lead us to hypothesize that distinct selection and evolutionary pressures act on the virus at the time of transmission and during the early phases of infection, and these may in turn affect the choice of bnAb combinations needed for protection against vertical transmission of HIV.

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