African Infants Research Articles

Gastrointestinal and respiratory morbidity when introducing eggs as complementary food: a randomised controlled trial in South African infants

We investigated the incidence and duration of morbidity symptoms among infants aged 6 to 9 months from a low socioeconomic community receiving one egg daily for 6 months. This was a secondary outcome of a randomised controlled trial (RCT) of 500 infants conducted in Jouberton, South Africa. The primary outcome was linear growth. Morbidity data were collected weekly using a symptoms diary and qualitative data with focus group discussions at the endpoint. Ethical approval was obtained from the North-West University Health Research Ethics Committee. The intervention group had a ~ 5% higher incidence of gastrointestinal morbidity (17.0%) compared to the control group (11.9%). Gastrointestinal morbidity without fever tended to be 1.4 times higher in the intervention group (OR: 1.43, 95% CI: 1.03, 1.93; P = 0.058) and tended to be 4 times higher with fever (OR: 4.07, 95% CI: 0.86, 19.23; P = 0.077). The duration of total gastrointestinal and respiratory morbidity was 1.5 days longer in the intervention group (β: 1.491; 95% CI 0.064, 2.918; P = 0.041). Complementary feeding with eggs may have contributed towards an increased risk for gastrointestinal morbidity.

Effect of RTS,S/AS01E vaccine booster dose on cellular immune responses in African infants and children

RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.

Associations Between Infant Formula Exposure, Housing Instability and Postneonatal Mortality Among Participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

To quantify infant mortality rates (IMR) using expanded racial categories, and to examine associations between infant formula exposure, housing instability and postneonatal mortality among Minnesota WIC Participants. Births in Minnesota from 2014 through 2019 (n = 404,102) and associated infant death records (n = 2034) were used to calculate neonatal and postneonatal rates using expanded racial categories. Those births that participated in the WIC program (n = 170,011) and their linked death records (n = 853) were analyzed using logistic regression to examine associations between formula exposure, housing instability, and postneonatal death. Postneonatal IMR was more than twice as prevalent among Black (African American) as East African immigrant infants (IMR = 3.9 vs 1.5). After adjustment for confounding (term status and nativity of mother (U.S. vs foreign born), infants exposed to formula by 28days were four times as likely to die in the postneonatal period as those without formula exposure (aOR = 4.0; 95% CI 3.2-4.9). WIC participants who experienced housing instability at birth were 1.7 times as likely to lose an infant in the postneonatal period (28 to 364days of age) as those in stable housing (aOR = 1.7; 95% CI 1.2, 2.4). Disaggregating Black mortality rates revealed inequities in infant mortality among Black families of varied backgrounds. Formula exposure and housing instability are modifiable risk factors associated with postneonatal mortality. Appropriate interventions to reduce barriers to breastfeeding and provide housing stability for vulnerable families could reduce disparities in postneonatal mortality.

Surface protein distribution in Group B Streptococcus isolates from South Africa and identifying vaccine targets through in silico analysis.

Group B Streptococcus (GBS) is a major cause of pneumonia, sepsis, and meningitis in infants younger than 3 months of age. Furthermore, GBS infection in pregnant women is associated with stillbirths and pre-term delivery. It also causes disease in immunocompromised adults and the elderly, but the highest incidence of the disease occurs in neonates and young infants. At this time, there are no licensed vaccines against GBS. Complete GBS genome sequencing has helped identify genetically conserved and immunogenic proteins, which could serve as vaccine immunogens. In this study, in silico reverse vaccinology method were used to evaluate the prevalence and conservation of GBS proteins in invasive and colonizing isolates from South African infants and women, respectively. Furthermore, this study aimed to predict potential GBS vaccine targets by evaluating metrics such as antigenicity, physico-chemical properties, subcellular localization, secondary and tertiary structures, and epitope prediction and conservation. A total of 648 invasive and 603 colonizing GBS isolate sequences were screened against a panel of 89 candidate GBS proteins. Ten of the 89 proteins were highly genetically conserved in invasive and colonizing GBS isolates, nine of which were computationally inferred proteins (gbs2106, SAN_1577, SAN_0356, SAN_1808, SAN_1685, SAN_0413, SAN_0990, SAN_1040, SAN_0226) and one was the surface Immunogenic Protein (SIP). Additionally, the nine proteins were predicted to be more antigenic than the SIP protein (antigenicity score of > 0.6498), highlighting their potential as GBS vaccine antigen targets.

S03-02 PFAS exposure, vaccine antibody concentrations, and risk of infection among West African infants

S03-02 PFAS exposure, vaccine antibody concentrations, and risk of infection among West African infants

Prevalence of asthma and wheeze among preschool and school‐aged children in Africa: A meta‐analysis

AbstractBackgroundIn Africa, asthma and wheezing are major health issues for children. There is a dearth of prior research examining the prevalence of asthma and wheezing in both preschool and school‐aged African children. Therefore, this meta‐analysis aimed to estimate the prevalence of asthma and wheezing in African infants and children aged 0 month to 8 years.MethodsWe conducted a thorough electronic search of Academic Search Complete, MEDLINE, CINAHL, Scopus, Web of Science, PubMed, and Web of Science to find papers published between January 2012 and July 2023. We reviewed only research that was published in English. Independently, two review authors examined the studies, extracted the data, and evaluated the research studies. A fixed effects model and STATA 17 software were used. Using I2, heterogeneity was assessed.ResultsWe considered 10 papers from Africa that examined the prevalence of asthma and/or wheezing in preschool and school‐aged children. Asthma prevalence ranged from 1.70% to 20.85% (n = 7 134 total participants), with a meta‐analysis showing an overall prevalence of 4.41% (95% CI: 3.95–4.87), with no heterogeneity (I2 < 0). The historical prevalence rate of wheezing ranged from 4.71% to 67.72% (n = 8769 total participants), with a meta‐analysis revealing an overall prevalence of 22.91% (95% CI: 22.12–23.70), with no heterogeneity (I2 < 0) and no significant differences observed between studies.ConclusionsAsthma and wheezing are prevalent among African preschool and school‐aged children, highlighting the need for comprehensive and localized research to address this public health issue.

Infant growth by INTERGROWTH-21st and Fenton Growth Charts: Predicting 1-year anthropometry in South African preterm infants.

Post-natal growth influences short- and long-term preterm infant outcomes. Different growth charts, such as the Fenton Growth Chart (FGC) and INTERGROWTH-21st Preterm Post-natal Growth Standards (IG-PPGS), describe different growth curves and targets. This study compares FGC- and IG-PPGS-derived weight-for-postmenstrual age z-score (WZ) up to 50 weeks postmenstrual age (PMA50) for predicting 1-year anthropometry in 321 South African preterm infants. The change in WZ from birth to PMA50 (ΔWZ, calculated using FGC and IG-PPGS) was correlated to age-corrected 1-year anthropometric z-scores for weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) and BMI-for-age (BMIZ), and categorically compared with rates of underweight (WAZ < -2), stunting (LAZ < -2), wasting (WLZ < -2) and overweight (BMIZ > + 2). Multivariable analyses explored the effects of other early-life exposures on malnutrition risk. At PMA50, mean WZ was significantly higher on IG-PPGS (-0.56 ± 1.52) than FGC (-0.90 ± 1.52; p < 0.001), but ΔWZ was similar (IG-PPGS -0.26 ± 1.23, FGC -0.11 ± 1.14; p = 0.153). Statistically significant ΔWZ differences emerged among small-for-gestational age infants (FGC -0.38 ± 1.22 vs. IG-PPGS -0.01 ± 1.30; p < 0.001) and appropriate-for-gestational age infants (FGC + 0.02 ± 1.08, IG-PPGS -0.39 ± 1.18; p < 0.001). Correlation coefficients of ΔWZ with WAZ, LAZ, WLZ and BMIZ were low (r < 0.45), though higher for FGC than IG-PPGS. Compared with IG-PPGS, ΔWZ < -1 on FGC predicted larger percentages of underweight (42% vs. 36%) and wasting (43% vs. 39%) and equal percentages of stunting (33%), while ΔWZ > + 1 predicted larger percentages overweight (57% vs. 38%). Both charts performed similarly in multivariable analysis. Differences between FGC and IG-PPGS are less apparent when considering ΔWZ, highlighting the importance of assessing growth as change over time, irrespective of growth chart.

High Prevalence of Unconfirmed Positive HIV PCR Test Results among African Infants with HIV Exposure in the International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium.

In a large, multi-regional cohort of African infants with HIV exposure, 44% of those with a positive HIV PCR lacked a confirmatory positive test. Efforts are needed to ensure high-fidelity implementation of HIV testing algorithms, so that all positive results are confirmed thereby reducing the risk of potentially false-positive results.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein-specific (CSP-specific) IgG predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

Syndromic Gastrointestinal Panel Diagnostic Tests Have Changed our Understanding of the Epidemiology of Yersiniosis-Foodborne Diseases Active Surveillance Network, 2010-2021.

In the US, yersinosis was understood to predominantly occur in winter and among Black or African American infants and Asian children. Increased use of culture-independent diagnostic tests (CIDTs) has led to marked increases in yersinosis diagnoses. We describe differences in the epidemiology of yersiniosis diagnosed by CIDT versus culture in 10 US sites, and identify determinants of health associated with diagnostic method. Annual reported incidence increased from 0.3/100 000 in 2010 to 1.3/100 000 in 2021, particularly among adults ≥18 years, regardless of race and ethnicity, and during summer months. The proportion of CIDT-diagnosed infections increased from 3% in 2012 to 89% in 2021. An ill person's demographic characteristics and location of residence had a significant impact on their odds of being diagnosed by CIDT. Improved detection due to increased CIDT use has altered our understanding of yersinosis epidemiology, however differential access to CIDTs may still affect our understanding of yersinosis.

Differences in Pertussis Incidence by Race and Ethnicity in the United States, 2010-2017.

An increased pertussis burden has been demonstrated among Hispanic or Latino and American Indian or Alaska Native (AI/AN) infants. However, data on potential disparities among other age and racial groups are limited. We analyzed pertussis cases reported through Enhanced Pertussis Surveillance from 2010 to 2017. Pertussis and severe pertussis incidence were calculated by race (White, Black or African American, AI/AN, and Asian or Pacific Islanders), ethnicity (Hispanic or Latino and non-Hispanic or non-Latino), and age. Compared with White persons, overall incidence was lower among Black or African American (incidence rate ratio [IRR], .57; 95% confidence interval [CI], .53-.61), AI/AN (IRR, 0.65; 95% CI, .58-.72), and Asian or Pacific Islander persons (IRR, 0.39; 95% CI, .35-.43). Overall incidence of pertussis was higher (1.5-fold; 95% CI, 1.37-1.60) among Hispanic or Latino compared with non-Hispanic or non-Latino adults, potentially related to household size or lower pertussis vaccine uptake among adult Hispanic or Latino cases. Severe pertussis incidence was similar among Black or African American and AI/AN persons compared with White persons. Among infants, severe pertussis incidence was 1.4-fold higher (95% CI, 1.03-1.82) among Black or African American infants than among White infants, and 2.1-fold higher (95% CI, 1.67-2.57) among Hispanic or Latino infants than non-Hispanic or non-Latino infants. The contrast between lower reported incidence but similar or higher severe pertussis incidence among Black or African American and AI/AN persons compared with White persons warrants further investigation and may reflect underdiagnosis or underreporting of mild disease.

Abundance of Selected Lipopolysaccharide-Rich Bacteria and Levels of Toll-like Receptor 4 and Interleukin 8 Expression Are Significantly Associated with Live Attenuated Rotavirus Vaccine Shedding among South African Infants.

Bacterial lipopolysaccharides (LPSs) have been shown to promote enteric viral infections. This study tested the hypothesis that elevated levels of bacterial LPS improve oral rotavirus vaccine replication in South African infants. Stool samples were collected from infants a week after rotavirus vaccination to identify vaccine virus shedders (n = 43) and non-shedders (n = 35). Quantitative real-time PCR was used to assay for selected LPS-rich bacteria, including Serratia marcescens, Pseudomonas aeruguinosa and Klebsiella pneumonia, and to measure the gene expression of bacterial LPS, host Toll-like Receptor 4 (TLR4) and Interleukin-8 (IL-8). The abundance of selected LPS-rich bacteria was significantly higher in vaccine shedders (median log 4.89 CFU/g, IQR 2.84) compared to non-shedders (median log 3.13 CFU/g, IQR 2.74), p = 0.006. The TLR4 and IL-8 gene expressions were increased four- and two-fold, respectively, in vaccine shedders versus non-shedders, but no difference was observed in the bacterial LPS expression, p = 0.09. A regression analysis indicated a significant association between the abundance of selected LPS-rich bacteria and vaccine virus shedding (Odds ratio 1.5, 95% CI = 1.10-1.89), p = 0.002. The findings suggest that harbouring higher counts of LPS-rich bacteria can increase the oral rotavirus vaccine take in infants.

A collaboration team to build social service partnerships within a safety-net health system

BackgroundTo facilitate safety-net healthcare system partnerships with community social service providers, the Los Angeles County Department of Health Services (LAC DHS) created a new collaboration team to spur cross-agency social and medical referral networks and engage communities affected by health disparities as part of a Sect. 1115 Medicaid waiver in Los Angeles County entitled Whole Person Care-Los Angeles (WPC-LA).MethodsThis observational research reviews three years of collaboration team implementation (2018–2020) through Medicaid-reportable engagement reports, a collaboration team qualitative survey on challenges, facilitators, and recommendations for community engagement. Member reflections for survey findings were conducted with the collaboration team and LAC DHS WPC-LA leadership.ResultsCollaboration team Medicaid engagement reports (n = 144) reported > 2,700 events, reaching > 70,000 individuals through cross-agency and community-partnered meetings. The collaboration team survey (n = 9) and member reflection sessions portrayed engagement processes through outreach, service assessments, and facilitation of service partnerships. The collaboration team facilitated community engagement processes through countywide workgroups on justice-system diversion and African American infant and maternal health. Recommendations for future safety net health system engagement processes included assessing health system readiness for community engagement and identifying strategies to build mutually beneficial social service partnerships.ConclusionsA dedicated collaboration team allowed for bi-directional knowledge exchange between county services, populations with lived experience, and social services, identifying service gaps and recommendations. Engagement with communities affected by health disparities resulted in health system policy recommendations and changes.

One-year anthropometric follow-up of South African preterm infants in kangaroo mother care: Which early-life factors predict malnutrition?

Preterm infants often have poor short- and long-term growth. Kangaroo mother care supports short-term growth, but longer-term outcomes are unclear. This study analysed longitudinally collected routine clinical data from a South African cohort of preterm infants (born <37 weeks gestation) attending the outpatient follow-up clinic of a tertiary-level hospital (Tshwane District, South Africa) for 1 year between 2012 and 2019. At 1 year, small-for-gestational age (SGA) and appropriate-for-gestational age (AGA) infants were compared with regard to age-corrected anthropometric z-scores (weight-for-age [WAZ], length-for-age [LAZ], weight-for-length [WLZ] and BMI-for-age [BMIZ]) and rates of underweight (WAZ < -2), stunting (LAZ < -2), wasting (WLZ < -2) and overweight (BMIZ> + 2). Multiple regression analysis was used to investigate associations between maternal/infant characteristics and rates of underweight, stunting, wasting and overweight. At 1 year, compared with AGA infants (n = 210), SGA infants (n = 111) had lower WAZ (-1.26 ± 1.32 vs. -0.22 ± 1.24, p < 0.001), LAZ (-1.50 ± 1.11 vs. -0.60 ± 1.06, p < 0.001), WLZ (-0.66 ± 1.31 vs. 0.11 ± 1.24, p < 0.001) and BMIZ (-0.55 ± 1.31 vs. 1.06 ± 1.23, p < 0.001), despite larger WAZ gains from birth (+0.70 ± 1.30 vs. +0.05 ± 1.30, p < 0.001). SGA infants had significantly more stunting (34.2% vs. 9.1%; p < 0.001), underweight (31.2% vs. 7.2%; p < 0.001) and wasting (12.6% vs. 4.3%, p = 0.012), with no difference in overweight (4.5% vs. 7.7%, p = 0.397). In multiple regression analysis, birth weight-for-GA z-score more consistently predicted 1-year malnutrition than SGA. Preterm-born SGA infants remain more underweight, stunted and wasted than their preterm-born AGA peers at 1 year, despite greater WAZ gains. Interventions for appropriate catch-up growth especially for SGA preterm infants are needed.

Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses.

Infants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid vaccine responses. We evaluated the gut microbiota of 82 South African (61 iHEU and 21 iHUU) and 196 Nigerian (141 iHEU and 55 iHUU) infants at <1 and 15 weeks of life by 16S rRNA gene sequencing. Anti-tetanus antibodies were measured by enzyme-linked immunosorbent assay at matched time points. Gut microbiota in the 278 included infants and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants, who were exclusively breastfed, drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among South African infants, even when limiting the analysis to exclusively breastfed infants. The Least Absolute Shrinkage and Selection Operator regression suggested that HIV exposure and gut microbiota were independently associated with tetanus titers at week 15, and that high passively transferred antibody levels, as seen in the Nigerian cohort, may mitigate these effects. In conclusion, in two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and setting, but both specific gut microbes and HIV exposure independently predicted humoral tetanus vaccine responses.IMPORTANCEGut microbiota plays an essential role in immune system development. Since infants HIV-exposed and uninfected (iHEU) are more vulnerable to infectious diseases than unexposed infants, we explored the impact of HIV exposure on gut microbiota and its association with vaccine responses. This study was conducted in two African countries with rapidly increasing numbers of iHEU. Infant HIV exposure did not substantially affect gut microbial succession, but geographic location had a strong effect. However, both the relative abundance of specific gut microbes and HIV exposure were independently associated with tetanus titers, which were also influenced by baseline tetanus titers (maternal transfer). Our findings provide insight into the effect of HIV exposure, passive maternal antibody, and gut microbiota on infant humoral vaccine responses.

Comparative prebiotic potential of galacto- and fructo-oligosaccharides, native inulin, and acacia gum in Kenyan infant gut microbiota during iron supplementation.

Iron fortification to prevent anemia in African infants increases colonic iron levels, favoring the growth of enteropathogens. The use of prebiotics may be an effective strategy to reduce these detrimental effects. Using the African infant PolyFermS gut model, we compared the effect of the prebiotics short-chain galacto- with long-chain fructo-oligosaccharides (scGOS/lcFOS) and native inulin, and the emerging prebiotic acacia gum, a branched-polysaccharide-protein complex consisting of arabinose and galactose, during iron supplementation on four Kenyan infant gut microbiota. Iron supplementation did not alter the microbiota but promoted Clostridioides difficile in one microbiota. The prebiotic effect of scGOS/lcFOS and inulin was confirmed during iron supplementation in all investigated Kenyan infant gut microbiota, leading to higher abundance of bifidobacteria, increased production of acetate, propionate, and butyrate, and a significant shift in microbiota composition compared to non-supplemented microbiota. The abundance of the pathogens Clostridium difficile and Clostridium perfringens was also inhibited upon addition of the prebiotic fibers. Acacia gum had no effect on any of the microbiota. In conclusion, scGOS/lcFOS and inulin, but not acacia gum, showed a donor-independent strong prebiotic potential in Kenyan infant gut microbiota. This study demonstrates the relevance of comparing fibers in vitro prior to clinical studies.

In-utero exposure to tenofovir disoproxil fumarate pre-exposure prophylaxis and growth metrics in HIV unexposed breastfed infants in South Africa: a post hoc analysis of the CAP 016 PrEP in pregnancy RCT.

We evaluated growth metrics in HIV unexposed African breastfed infants in the first 18 months of life in association with in-utero exposure to Tenofovir Diphosphate Fumarate (TDF) containing pre-exposure prophylaxis (PrEP). We conducted a secondary data analysis of a TDF-PrEP randomized control trial (CAP016 RCT). Pregnant women without HIV were randomized to initiating TDF-PrEP in pregnancy (Immediate-PrEP-IP) or deferred initiation of TDF-PrEP at cessation of breastfeeding (Deferred-PrEP-DP). Infant weight (W), length (L), and head circumference (HC) were measured at birth and 6, 26, 50, and 74 weeks of age. Stored dried blood spot samples from pregnant women randomized to the IP arm were used to measure tenofovir-diphosphate (TFV-DP) levels. Age-stratified mean weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), and head circumference-for-age (HCAZ) Z-scores were compared between infants exposed to varying TFV-DP concentrations and infants in the DP arm. A total of 455 mother-infant pairs were included in the secondary analysis, 228 in the IP arm and 227 in the DP arm. WAZ, LAZ, WLZ, and HCAZ scores were comparable between infants in the Deferred-PrEP arm and Immediate-PrEP arm. In a mixed-effects linear regression model adjusting for maternal age, body mass index, socioeconomic and newborn characteristics, in-utero exposure to varying TFV-DP levels was not associated with WAZ (β = -0.52), LAZ (β = -0.46), WLZ (β = -0.43) and HCAZ (β = -0.11) scores over time. There was no evidence of an association between growth metrics in the first 18 months of life and in-utero exposure to TFV-DP among breastfed HIV unexposed infants.

Borderline hypernatraemia and mortality rates in South African infants: A single-centre observational study

Background. In children, hypernatraemia occurs most commonly in infants (younger than 1 year). Although hypernatraemia is associated with high mortality and morbidity rates, it is variably defined in the paediatric literature as either serum sodium ≥150 mmol/L or serum sodium &gt;145 mmol/L. In hospitalised adults, a serum sodium level &gt;145 mmol/L but &lt;150 mmol/L (called borderline hypernatraemia) has recently been identified as an independent risk factor for mortality. There are limited data about a potential association between borderline hypernatraemia and mortality in infants. Objectives. To determine whether borderline hypernatraemia is associated with increased mortality in hospitalised infants. Methods. We conducted a single-centre, retrospective observational study of 8 343 infants admitted to a tertiary-level academic hospital in Johannesburg, South Africa, of whom 254 had borderline hypernatraemia, 376 had hypernatraemia (serum sodium ≥150 mmol/L), and 7 713 did not have hypernatraemia. Mortality rates were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results. In 254 infants with borderline hypernatraemia, 115 (45.3%) were neonates (≤28 days old) and 140 (55.1%) were male. In 139 infants &gt;28 days old with borderline hypernatraemia, the mortality rate (n=9/139; 6.5%) was significantly higher than the mortality rate observed in infants without hypernatraemia (n=194/5 857; 3.3%) (OR 2.02; 95% CI 1.03 - 3.98). Conclusion. Borderline hypernatraemia may be a risk factor associated with higher mortality in hospitalised infants. Prospective studies are required to determine whether borderline hypernatraemia contributes independently to mortality risk in hospitalised infants.

383. Pharmacokinetics and Safety in Healthy Adults of RSM01, a Novel RSV Monoclonal Antibody, and Population PK Modeling to Support Pediatric Development

Abstract Background RSV is a common cause of infant respiratory infection and hospitalization. RSM01 is a novel anti-RSV mAb targeting the F glycoprotein essential for viral entry with a YTE mutation for half-life extension. Phase 1a PK and safety results are presented, along with an adult population PK model used to predict pediatric exposures via simulation. Methods In this double-blind Phase 1a study, healthy males and non-childbearing females aged 18-49 yrs were randomized 6:1 within dose cohorts to receive a single dose of RSM01 or placebo (PBO) in the following RSM01 dose sequence: 300mg IV, 300mg IM or 1000mg IV, 3000mg IV and cohort at 600mg IM. Serial serum samples were taken to measure RSM01 PK using a validated immunoassay method. A noncompartmental analysis (NCA) was conducted, and a population PK model was developed to characterize adult PK and predict pediatric PK using allometric scaling. Pediatric RSM01 PK was predicted for African infants at different IM doses. Results Overall, 56 participants received RSM01 (n=48) or PBO (n=8): median age 30 yrs (range 19-48), 52% male (n = 29), 66% White (n=37), median BMI 24.6 kg/m2 (range 18.1-29.4). 12/48 (25%) RSM01 recipients and 2/8 (25%) PBO recipients reported an AE, with no hypersensitivity reactions, serious AEs, or deaths reported. The median Tmax was ∼6–7 days after IM injection. Cmax and AUClast increased dose proportionally following IV administration. RSM01 adult PK was characterized using a two-compartment model with first-order elimination. IM absorption was described using a zero-order rate constant. Inter-individual variability was included for clearance (CL), central and peripheral volumes (V2 and V3). The RSM01 model estimated that distribution and a terminal half-life were 1.3 and 79.1 days, respectively, and IM bioavailability was ∼82%. The model predicted that following a 50 mg IM dose, median serum RSM01 concentration on day 150 in African infants 0-12 months old to be ∼ 28 mcg/mL, higher than the target exposure based on preclinical models (6.8 mcg/mL). Serum RSM01 NCA PK summary Note: AUClast and Cmax values are presented as geometric mean (CV). Tmax and Tlast are presented as median (min-max). Arithmetic Mean (±SD) Serum RSM01 Concentration-Time Curve by Treatment Note: Horizontal blue dashed line represents the target exposure based on preclinical models (6.8 mcg/mL). Conclusion RSM01 was shown to be well tolerated in healthy adults. Its long half-life and the predicted infant PK profiles support further pediatric development and indicate the potential for dosing once every RSV season. Disclosures Micha Levi, PhD, Bill &amp; Melinda Gates Medical Research Institute: Salary as a full-time employee Shayne Watson, MSc, Bill &amp; Melinda Gates Medical Research Institute: Salary as a full-time employee Dale Taylor, MD, Sanara Medtech Inc: Stocks/Bonds Luisa M. Stamm, MD, PhD, Bill &amp; Melinda Gates Medical Research Institute: Salary as a full-time employee Michael W. Dunne, MD, Bill &amp; Melinda Gates Medical Research Institute: Salary as a full-time employee

Long-term continuous cultivation of Kenyan infant fecal microbiota using the host adapted PolyFermS model

Appropriate in vitro models to investigate the impact of novel nutritional strategies on the gut microbiota of infants living in rural Africa are scarce. Here, we aimed to develop such a continuous gut fermentation model based on the PolyFermS platform, which allows controlled and stable long-term cultivation of colon microbiota in conditions akin the host. Nine immobilized Kenyan infant fecal microbiota were used as inoculum for continuous PolyFermS colon models fed with medium mimicking the weaning infant diet. Fructo-oligosaccharides (FOS) supplementation (1, 4 and 8 g/L) and cultivation pH (5.8 and 6.3) were investigated stepwise. Conditions providing a close match between fecal and in vitro microbiota (pH 5.8 with 1 g/L FOS) were selected for investigating long-term stability of four Kenyan infant PolyFermS microbiota. The shared fraction of top bacterial genera between fecal and in vitro microbiota was high (74–89%) and stable during 107 days of continuous cultivation. Community diversity was maintained and two distinct fermentation metabolite profiles of infant fecal microbiota were observed. Three propiogenic and one butyrogenic metabolite profile of infant fecal microbiota established from day 8 onwards and stayed stable. We present here the first rationally designed continuous cultivation model of African infant gut microbiota. This model will be important to assess the effect of dietary or environmental factors on the gut microbiota of African infants with high enteropathogen exposure.