Journal Articles

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Antibiotic Use In Utero and Early Life and Risk of Chronic Childhood Conditions in New Zealand: Protocol for a Data Linkage Retrospective Cohort Study
(JMIR Publications, 2025-02-28) Ram S; Corbin M; 't Mannetje A; Eng A; Kvalsig A; Baker M; Douwes J
Background: The incidence of many common chronic childhood conditions has increased globally in the past few decades, which has been suggested to be potentially attributed to antibiotic overuse leading to dysbiosis in the gut microbiome. Objective: This linkage study will assess the role of antibiotic use in utero and in early life in the development of type 1 diabetes (T1D), attention-deficit/hyperactive disorder (ADHD), and inflammatory bowel disease. Methods: The study design involves several retrospective cohort studies using linked administrative health and social data from Statistics New Zealand’s Integrated Data Infrastructure. It uses data from all children who were born in New Zealand between October 2005 and December 2010 (N=334,204) and their mothers. Children’s antibiotic use is identified for 4 time periods (at pregnancy, at ≤1 year, at ≤2 years, and at ≤5 years), and the development of T1D, ADHD, and inflammatory bowel disease is measured from the end of the antibiotic use periods until death, emigration, or the end of the follow-up period (2021), whichever came first. Children who emigrated or died before the end of the antibiotic use period are excluded. Cox proportional hazards regression models are used while adjusting for a range of potential confounders. Results: As of September 2024, data linkage has been completed, involving the integration of antibiotic exposure and outcome variables for 315,789 children. Preliminary analyses show that both prenatal and early life antibiotic consumption is associated with T1D. Full analyses for all 3 outcomes will be completed by the end of 2025. Conclusions: This series of linked cohort studies using detailed, complete, and systematically collected antibiotic prescription data will provide critical new knowledge regarding the role of antibiotics in the development of common chronic childhood conditions. Thus, this study has the potential to contribute to the development of primary prevention strategies through, for example, targeted changes in antibiotic use.
The home literacy environment of school-age autistic children with high support needs.
(John Wiley and Sons, 2024-08-01) Westerveld MF; Malone SA; Clendon S; Bowen R; Hayley G; Paynter J
BACKGROUND: As a group, autistic children with high support needs (with adaptive functioning in the range of an intellectual disability) are at risk of significant literacy difficulties. We investigated the parent-reported home literacy environment of this group of children. METHOD: Sixty-two parents of autistic children (4.5 to 18.25 years) attending an autism-specific school completed a home literacy survey reporting on their child's: (1) alphabet knowledge, (2) interest in reading, (3) activities/interactions around books, (4) reading ability, and (5) writing ability. RESULTS: We found significant positive correlations between parent-reported child interest in reading and literacy-related interactions and skills, but not with child age. Children using spoken words to communicate obtained significantly greater scores on four home-literacy subscales, but not on reading interest. CONCLUSIONS: A better understanding of the home literacy activities of autistic children with high-support needs is needed to inform educational practices aimed at promoting literacy development in this vulnerable population.
Advanced theory of mind and children's prosocial lie-telling in middle childhood: A training study
(Elsevier Inc., 2024-10-01) Gao Q; Chen P; Huang Q; Wang Z
Children's advanced theory of mind (AToM) is concurrently associated with their prosocial lie-telling. However, the causal link between AToM and prosocial lie-telling has not yet been demonstrated. To address this gap, the current study adopted a training paradigm and investigated the role of AToM in children's prosocial lie-telling in middle childhood. A total of 66 9- and 10-year-old children who did not demonstrate any prosocial lie-telling in a disappointment gift paradigm at the baseline were recruited and randomly assigned to either the experimental group (n = 32) or an active control group (n = 34). The experimental group underwent a conversation-based training program of four sessions. The results showed significantly greater gains in AToM at the posttest for the experimental group children compared with the control group children, controlling for family socioeconomic status, children's literacy score, working memory, and inhibition. More important, the experimental group children were more likely to tell prosocial lies than the control group, even after controlling for the pretest AToM and other covariates. However, the training effects faded at the 6-month follow-up test after the training's completion. These findings provide the first evidence for the causal role of AToM in the development of prosocial lie-telling in middle childhood. The fade-out effect is discussed in the context of educational interventions.
Molecular epidemiology and whole genome sequencing analysis of clinical Mycobacterium bovis from Ghana.
(PLOS, 2019-03-04) Otchere ID; van Tonder AJ; Asante-Poku A; Sánchez-Busó L; Coscollá M; Osei-Wusu S; Asare P; Aboagye SY; Ekuban SA; Yahayah AI; Forson A; Baddoo A; Laryea C; Parkhill J; Harris SR; Gagneux S; Yeboah-Manu D; Spigelman M
Background Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen. Methods Mycobacterium bovis (15) among 1755 M. tuberculosis complex (MTBC) isolated between 2012 and 2014 were characterized and analyzed for associated patient demography and other risk factors. Five of the M. bovis isolates were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes. Results Mycobacterium bovis was isolated from 3/560(0.5%) females and 12/1195(1.0%) males with pulmonary TB. The average age of M. bovis infected cases was 46.8 years (7-72years). TB patients from the Northern region of Ghana (1.9%;4/212) had a higher rate of infection with M. bovis (OR = 2.7,p = 0.0968) compared to those from the Greater Accra region (0.7%;11/1543). Among TB patients with available HIV status, the odds of isolating M. bovis from HIV patients (2/119) was 3.3 higher relative to non-HIV patients (4/774). Direct contact with livestock or their unpasteurized products was significantly associated with bTB (p<0.0001, OR = 124.4,95% CI = 30.1–508.3). Two (13.3%) of the M. bovis isolates were INH resistant due to the S315T mutation in katG whereas one (6.7%) was RIF resistant with Q432P and I1491S mutations in rpoB. M. bovis from Ghana resolved as mono-phyletic branch among mostly M. bovis from Africa irrespective of the host and were closest to the root of the global M. bovis phylogeny. M. bovis-specific amino acid mutations were detected among MTBC core genes such as mce1A, mmpL1, pks6, phoT, pstB, glgP and Rv2955c. Additional mutations P6T in chaA, G187E in mgtC, T35A in Rv1979c, S387A in narK1, L400F in fas and A563T in eccA1 were restricted to the 5 clinical M. bovis from Ghana. Conclusion Our data indicate potential zoonotic transmission of bTB in Ghana and hence calls for intensified public education on bTB, especially among risk groups..
Effect of Vaccination on Pneumococci Isolated from the Nasopharynx of Healthy Children and the Middle Ear of Children with Otitis Media in Iceland.
(American Society for Microbiology, 2018-11-27) Quirk SJ; Haraldsson G; Erlendsdóttir H; Hjálmarsdóttir MÁ; van Tonder AJ; Hrafnkelsson B; Sigurdsson S; Bentley SD; Haraldsson Á; Brueggemann AB; Kristinsson KG
Vaccination with pneumococcal conjugate vaccines (PCVs) disrupts the pneumococcal population. Our aim was to determine the impact of the 10-valent PCV on the serotypes, genetic lineages, and antimicrobial susceptibility of pneumococci isolated from children in Iceland. Pneumococci were collected between 2009 and 2017 from the nasopharynges of healthy children attending 15 day care centers and from the middle ears (MEs) of children with acute otitis media from the greater Reykjavik capital area. Isolates were serotyped and tested for antimicrobial susceptibility. Whole-genome sequencing (WGS) was performed on alternate isolates from 2009 to 2014, and serotypes and multilocus sequence types (STs) were extracted from the WGS data. Two study periods were defined: 2009 to 2011 (PreVac) and 2012 to 2017 (PostVac). The overall nasopharyngeal carriage rate was similar between the two periods (67.3% PreVac and 61.5% PostVac, P = 0.090). Vaccine-type (VT) pneumococci decreased and nonvaccine-type (NVT) pneumococci (serotypes 6C, 15A, 15B/C, 21, 22F, 23A, 23B, 35F, and 35B) significantly increased in different age strata post-PCV introduction. The total number of pneumococci recovered from ME samples significantly decreased as did the proportion that were VTs, although NVT pneumococci (6C, 15B/C, 23A, and 23B) increased significantly. Most serotype 6C pneumococci were multidrug resistant (MDR). Serotype 19F was the predominant serotype associated with MEs, and it significantly decreased post-PCV introduction: these isolates were predominantly MDR and of the Taiwan19F-14 PMEN lineage. Overall, the nasopharyngeal carriage rate remained constant and the number of ME-associated pneumococci decreased significantly post-PCV introduction; however, there was a concomitant and statistically significant shift from VTs to NVTs in both collections of pneumococci.
Differences in Compositions of Gut Bacterial Populations and Bacteriophages in 5-11 Year-Olds Born Preterm Compared to Full Term
(Frontiers Media S.A., 2020-06-16) Jayasinghe TN; Vatanen T; Chiavaroli V; Jayan S; McKenzie EJ; Adriaenssens E; Derraik JGB; Ekblad C; Schierding W; Battin MR; Thorstensen EB; Cameron-Smith D; Forbes-Blom E; Hofman PL; Roy NC; Tannock GW; Vickers MH; Cutfield WS; O'Sullivan JM; Shkoporov A
Preterm infants are exposed to major perinatal, post-natal, and early infancy events that could impact on the gut microbiome. These events include infection, steroid and antibiotic exposure, parenteral nutrition, necrotizing enterocolitis, and stress. Studies have shown that there are differences in the gut microbiome during the early months of life in preterm infants. We hypothesized that differences in the gut microbial composition and metabolites in children born very preterm persist into mid-childhood. Participants were healthy prepubertal children aged 5-11 years who were born very preterm (≤32 weeks of gestation; n = 51) or at term (37-41 weeks; n = 50). We recorded the gestational age, birth weight, mode of feeding, mode of birth, age, sex, and the current height and weight of our cohort. We performed a multi'omics [i.e., 16S rRNA amplicon and shotgun metagenomic sequencing, SPME-GCMS (solid-phase microextraction followed by gas chromatography-mass spectrometry)] analysis to investigate the structure and function of the fecal microbiome (as a proxy of the gut microbiota) in our cross-sectional cohort. Children born very preterm were younger (7.8 vs. 8.3 years; p = 0.034), shorter [height-standard deviation score (SDS) 0.31 vs. 0.92; p = 0.0006) and leaner [BMI (body mass index) SDS -0.20 vs. 0.29; p < 0.0001] than the term group. Children born very preterm had higher fecal calprotectin levels, decreased fecal phage richness, lower plasma arginine, lower fecal branched-chain amino acids and higher fecal volatile (i.e., 3-methyl-butanoic acid, butyrolactone, butanoic acid and pentanoic acid) profiles. The bacterial microbiomes did not differ between preterm and term groups. We speculate that the observed very preterm-specific changes were established in early infancy and may impact on the capacity of the very preterm children to respond to environmental changes.
Evaluation of Protein Adequacy From Plant-Based Dietary Scenarios in Simulation Studies: A Narrative Review
(Elsevier Inc on behalf of the American Society for Nutrition, 2024-02) Soh BXP; Smith NW; R von Hurst P; McNabb WC
Although a diet high in plant foods can provide beneficial nutritional outcomes, unbalanced and restrictive plant-based diets may cause nutrient deficiencies. Protein intake from these diets is widely discussed, but the comparison of animal and plant proteins often disregards amino acid composition and digestibility as measurements of protein quality. Poor provision of high-quality protein may result in adverse outcomes, especially for individuals with increased nutrient requirements. Several dietary modeling studies have examined protein adequacy when animal-sourced proteins are replaced with traditional and novel plant proteins, but no review consolidating these findings are available. This narrative review aimed to summarize the approaches of modeling studies for protein intake and protein quality when animal-sourced proteins are replaced with plant foods in diet simulations and examine how these factors vary across age groups. A total of 23 studies using dietary models to predict protein contribution from plant proteins were consolidated and categorized into the following themes-protein intake, protein quality, novel plant-based alternatives, and plant-based diets in special populations. Protein intake from plant-based diet simulations was lower than from diets with animal-sourced foods but met country-specific nutrient requirements. However, protein adequacy from some plant-sourced foods were not met for simulated diets of children and older adults. Reduced amino acid adequacy was observed with increasing intake of plant foods in some scenarios. Protein adequacy was generally dependent on the choice of substitution with legumes, nuts, and seeds providing greater protein intake and quality than cereals. Complete replacement of animal to plant-sourced foods reduced protein adequacy when compared with baseline diets and partial replacements.
Using network analysis to identify factors influencing the heath-related quality of life of parents caring for an autistic child
(Elsevier Ltd., 2024-09-01) Shepherd D; Buchwald K; Siegert RJ; Vignes M
BACKGROUND: Raising an autistic child is associated with increased parenting stress relative to raising typically developing children. Increased parenting stress is associated with lower parent wellbeing, which in turn can negatively impact child wellbeing. AIMS: The current study sought to quantify parenting stress and parent health-related quality of life (HRQOL) in the autism context, and further understand the relationship between them by employing a relatively novel statistical method, Network Analysis. METHODS AND PROCEDURES: This cross-sectional study involved 476 parents of an autistic child. Parents completed an online survey requesting information on parent and child characteristics, parent's perceptions of their autistic child's symptoms and problem behaviours, and assessed their parenting stress and HRQOL. OUTCOMES AND RESULTS: Relative to normative data, parent HRQOL was significantly lower in terms of physical health and mental wellbeing. The structure extracted by the Network Analysis indicated that child age and externalising behaviours were the main contributors to parenting stress, and that externalising behaviours, ASD core behavioural symptoms, and parenting stress predicted HRQOL. CONCLUSIONS AND IMPLICATIONS: Parental responses to child-related factors likely determine parent HRQOL. Findings are discussed in relation to the transactional model, emphasising the importance of both parent and child wellbeing.
Severe weather events and cryptosporidiosis in Aotearoa New Zealand: A case series of space-time clusters.
(Cambridge University Press, 2024-04-15) Grout L; Hales S; Baker MG; French N; Wilson N
Occurrence of cryptosporidiosis has been associated with weather conditions in many settings internationally. We explored statistical clusters of human cryptosporidiosis and their relationship with severe weather events in New Zealand (NZ). Notified cases of cryptosporidiosis from 1997 to 2015 were obtained from the national surveillance system. Retrospective space-time permutation was used to identify statistical clusters. Cluster data were compared to severe weather events in a national database. SaTScan analysis detected 38 statistically significant cryptosporidiosis clusters. Around a third (34.2%, 13/38) of these clusters showed temporal and spatial alignment with severe weather events. Of these, nearly half (46.2%, 6/13) occurred in the spring. Only five (38%, 5/13) of these clusters corresponded to a previously reported cryptosporidiosis outbreak. This study provides additional evidence that severe weather events may contribute to the development of some cryptosporidiosis clusters. Further research on this association is needed as rainfall intensity is projected to rise in NZ due to climate change. The findings also provide further arguments for upgrading the quality of drinking water sources to minimize contamination with pathogens from runoff from livestock agriculture.
Evaluating active leprosy case identification methods in six districts of Nepal.
(BioMed Central Ltd., 2023-12-06) Mahato RK; Ghimire U; Lamsal M; Bajracharya B; Poudel M; Napit P; Lama K; Dahal G; Hayman DTS; Karna AK; Pandey BD; Das CL; Paudel KP
BACKGROUND: Nepal has achieved and sustained the elimination of leprosy as a public health problem since 2009, but 17 districts and 3 provinces with 41% (10,907,128) of Nepal's population have yet to eliminate the disease. Pediatric cases and grade-2 disabilities (G2D) indicate recent transmission and late diagnosis, respectively, which necessitate active and early case detection. This operational research was performed to identify approaches best suited for early case detection, determine community-based leprosy epidemiology, and identify hidden leprosy cases early and respond with prompt treatment. METHODS: Active case detection was undertaken in two Nepali provinces with the greatest burden of leprosy, Madhesh Province (40% national cases) and Lumbini Province (18%) and at-risk prison populations in Madhesh, Lumbini and Bagmati provinces. Case detection was performed by (1) house-to-house visits among vulnerable populations (n = 26,469); (2) contact examination and tracing (n = 7608); in Madhesh and Lumbini Provinces and, (3) screening prison populations (n = 4428) in Madhesh, Lumbini and Bagmati Provinces of Nepal. Per case direct medical and non-medical costs for each approach were calculated. RESULTS: New case detection rates were highest for contact tracing (250), followed by house-to-house visits (102) and prison screening (45) per 100,000 population screened. However, the cost per case identified was cheapest for house-to-house visits [Nepalese rupee (NPR) 76,500/case], followed by contact tracing (NPR 90,286/case) and prison screening (NPR 298,300/case). House-to-house and contact tracing case paucibacillary/multibacillary (PB:MB) ratios were 59:41 and 68:32; female/male ratios 63:37 and 57:43; pediatric cases 11% in both approaches; and grade-2 disabilities (G2D) 11% and 5%, respectively. Developing leprosy was not significantly different among household and neighbor contacts [odds ratios (OR) = 1.4, 95% confidence interval (CI): 0.24-5.85] and for contacts of MB versus PB cases (OR = 0.7, 95% CI 0.26-2.0). Attack rates were not significantly different among household contacts of MB cases (0.32%, 95% CI 0.07-0.94%) and PB cases (0.13%, 95% CI 0.03-0.73) (χ2 = 0.07, df = 1, P = 0.9) and neighbor contacts of MB cases (0.23%, 0.1-0.46) and PB cases (0.48%, 0.19-0.98) (χ2 = 0.8, df = 1, P = 0.7). BCG vaccination with scar presence had a significant protective effect against leprosy (OR = 0.42, 0.22-0.81). CONCLUSIONS: The most effective case identification approach here is contact tracing, followed by house-to-house visits in vulnerable populations and screening in prisons, although house-to-house visits are cheaper. The findings suggest that hidden cases, recent transmission, and late diagnosis in the community exist and highlight the importance of early case detection.

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