Repurposed drugs in combinations exert additive anti-chikungunya virus activity: an in-vitro study.

Chikungunya virus (CHIKV) infection causes chikungunya, a viral disease that currently has no specific antiviral treatment. Several repurposed drug candidates have been investigated for the treatment of the disease. In order to improve the efficacy of the known drugs, combining drugs for treatment is a promising approach. The current study was undertaken to explore the antiviral activity of a combination of repurposed drugs that were reported to have anti-CHIKV activity. We explored the effect of different combinations of six effective drugs (2-fluoroadenine, emetine, lomibuvir, enalaprilat, metyrapone and resveratrol) at their non-toxic concentrations against CHIKV under post infection treatment conditions in Vero cells. Focus-forming unit assay, real time RT-PCR, immunofluorescence assay, and western blot were used to determine the virus titre. The results revealed that the combination of 2-fluoroadenine with either metyrapone or emetine or enalaprilat exerted inhibitory activity against CHIKV under post-infection treatment conditions. The effect of these drug combinations was additive in nature compared to the effect of the individual drugs. The results suggest an additive anti-viral effect of these drug combinations against CHIKV. The findings could serve as an outline for the development of an innovative therapeutic approach in the future to treat CHIKV-infected patients.

Phylo-geo haplotype network-based characterization of SARS-CoV-2 strains circulating in India (2020-2022).

Background & objectives Genetic analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains circulating in India during 2020-2022 was carried out to understand the evolution of potentially expanding and divergent clades. Methods SARS-CoV-2 sequences (n=612) randomly selected from among the sequences of samples collected through a nationwide network of Virus Research Diagnostic Laboratories during 2020 (n=1532) and Indian sequences available in Global Initiative on Sharing All Influenza Data during March 2020-March 2022 (n=53077), were analyzed using the phylo-geo haplotype network approach with reference to the Wuhan prototype sequence. Results On haplotype analysis, 420 haplotypes were revealed from 643 segregating sites among the sequences. Haplotype sharing was noted among the strains from different geographical regions. Nevertheless, the genetic distance among the viral haplotypes from different clades could differentiate the strains into distinct haplo groups regarding variant emergence. Interpretation & conclusions The haplotype analysis revealed that the G and GR clades were co-evolved and an epicentrefor the evolution of the GH, GK and GRA clades. GH was more frequently identified in northern parts of India than in other parts, whereas GK was detected less in north India than in other parts. Thus, the network analysis facilitated a detailed illustration of the pathways of evolution and circulation of SARS-CoV-2 variants.

Epidemiology and assessment of Hepatitis B positive children in Western Australia.

AIM: To describe the characteristics of patients with chronic hepatitis B (CHB) presenting to a tertiary paediatric hospital in Perth, Western Australia. Review of implementation of previous follow-up recommendations for the cohort was also undertaken. METHOD: A retrospective data analysis of all individuals aged between 0 and 17 years presenting to the tertiary children's hospital who were hepatitis B surface antigen (HBsAg) positive over 8 years (2013-2020). Demographic features, clinical progress and follow up are described, including proportion transferred to adult services. RESULTS: Seventy-four patients were identified to have CHB; mean age at diagnosis 11 years; standard deviation 4 years; 41 (55%) male. Cultural and ethnolinguistic diversity was high; 74% (n = 55) were from refugee-like backgrounds. Many did not demonstrate English proficiency (23/40; 75%) and 7 (10%) Australian born including 4 patients who were Aboriginal. Most patients (58%) with CHB were in the hepatitis B e antigen-positive chronic infection phase with no intervention provided. Seventeen children had undergone liver ultrasonography and one underwent liver biopsy; none received antiviral treatment. Follow up was concerning; 28 (38%) had at least one clinic non-attendance, 24 (32%) lost to follow-up and interpreter utilisation was poorly documented. Thirty-nine (53%) were transferred to adult services with only 56% attending follow-up. CONCLUSION: CHB burden is higher in those from culturally and ethnolinguistically diverse backgrounds. There is a significant loss to follow-up and suboptimal transfer to adult services. Improved recall, education and referral processes are necessary to overcome language, socioeconomic and cultural barriers. Although childhood complications are infrequent, longitudinal monitoring is crucial to prevent long-term complications and adult morbidity.

Understanding the resurgence of chikungunya virus during 2020-2021 in Pune, India, based on genomic analyses: A seven year study.

A surge in chikungunya was observed during 2020-21 in Pune district of Maharashtra, India. Whole genome sequencing and phylogenetic analysis of 21 samples/sequences revealed them as Indian ocean lineage of East Central South African genotype. Two distinct sequence clusters were found to circulate during 2020-21; one with E1:K211E and E2:V264A mutations while the other had E1:I317V mutation along with E1:K211E and E2: V264A mutations. The former, the predominant cluster (n = 18), clustered with chikungunya virus (CHIKV) strains of pre 2014 period while the latter (n = 3) clustered with 2016-2018 period Indian strains. Though E1: A226V was not detected in any of the 21 sequences, several unique mutations were detected in the strains which might have played key roles in the enhanced virus transmission during the period. The study highlights parallel evolution, introduction from the neighboring regions and cocirculation of two sequence clusters of CHIKV in Pune. The complete genome data can be useful to determine how the circulating strains differ from candidate vaccines and might help to predict the protective efficacy of chikungunya vaccine candidates.

Repurposing of artesunate, an antimalarial drug, as a potential inhibitor of hepatitis E virus.

Hepatitis E virus (HEV) is endemic in several developing countries of Africa and Asia. It mainly causes self-limiting waterborne infections, in either sporadic or outbreak form. Recently, HEV was shown to cause chronic infections in immunosuppressed individuals. Ribavirin and interferon, the current off-label treatment options for hepatitis E, have several side effects. Hence, there is a need for new drugs. We evaluated the antimalarial drug artesunate (ART) against genotype 1 HEV (HEV-1) and HEV-3 using a virus-replicon-based cell culture system. ART exhibited 59% and 43% inhibition of HEV-1 and HEV-3, respectively, at the highest nontoxic concentration. Computational molecular docking analysis showed that ART can bind to the helicase active site (affinity score, -7.4 kcal/mol), indicating its potential to affect ATP hydrolysis activity. An in vitro ATPase activity assay of the helicase indeed showed 24% and 55% inhibition at 19.5 µM (EC50) and 78 µM concentrations of ART, respectively. Since ATP is a substrate of RNA-dependent RNA polymerase (RdRp) as well, we evaluated the effect of ART on the enzymatic activity of the viral polymerase. Interestingly, ART showed 26% and 40% inhibition of the RdRp polymerase activity at 19.5 µM and 78 µM concentrations of ART, respectively. It could be concluded from these findings that ART inhibited replication of both HEV-1 and HEV-3 by directly targeting the activities of the viral enzymes helicase and RdRp. Considering that ART is known to be safe in pregnant women, we think this antimalarial drug deserves further evaluation in animal models.

Perspectives of culturally and linguistically diverse families in the management of children with type 1 diabetes in Western Australia.

OBJECTIVES: Children with Type 1 diabetes (T1D) from different ethnic backgrounds are growing in proportion in clinical practice and tend to have a higher risk of poor health outcomes. The study aimed to investigate the perspectives of culturally and linguistically diverse families in the management of children with T1D in Western Australia. DESIGN: A generic qualitative approach was used. Families of children and adolescents with T1D with first-generation African, Asian or Middle Eastern background were invited to participate in a semi-structured interview. The interviews were audio-recorded, transcribed and analysed thematically. Demographic, clinical and socio-economic data were collected from all participants. RESULTS: Fifteen families (27% African, 33% Middle Eastern, 40% Asian) participated in the study. The mean (SD) age of the child with T1D was 10.2 (5.1) years, had diabetes for 2.9 (1.6) years and an average HbA1c of 67 (15) mmol/mol. Four main themes were identified through qualitative analysis. 'Dietary challenges': lack of adequate food resources posed a barrier to determine carbohydrate amount in traditional meals; 'Linguistic challenges': inadequate reading and language skills affected comprehension of written information and the desire for pictorial resources was reported; 'Limited Support': absence of extended family made management of T1D difficult; and 'Knowledge': a key facilitator, which was acquired through clinic education, enabled families to develop skills to effectively manage T1D. CONCLUSION: The study highlights the need to consider cultural diversity, psychosocial needs, English proficiency and health literacy when assessing and planning diabetes education. These findings will be useful to formulate a more culturally sensitive approach to diabetes education to improve care and outcomes for young people with T1D from culturally and linguistically diverse families.

Anti-Dengue Activity of Lipophilic Fraction of Ocimum basilicum L. Stem.

Ocimum basilicum L. is used to cure many types of fever in traditional medicine. This study aims to explore the antiviral activity of the lipophilic fraction of the stem of O. basilicum (LFOB) against dengue virus (DENV) and chikungunya virus (CHIKV). The LFOB was analyzed using GC-FID and GC-MS. The antiviral activity of LFOB was studied using the Vero CCL-81 cell line. The cytotoxicity assay was performed using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). In vitro antiviral activity and FFU assay were used to determine and confirm antiviral activity against DENV and CHIKV. Twenty-six compounds were identified in LFOB using GC/MS. The most abundant compounds were ß-sitosterol (22.9%), stigmasterol (18.7%), and campesterol (12.9%). Significant reduction in DENV titre was observed under pre- and post-infection treatment conditions at a concentration of 3.125 µg/mL, but no anti-CHIKV activity was observed. Our earlier and the present AutoDock-Vina-based in silico docking study revealed that ß-sitosterol and stigmasterol could form strong interactions with the DENV E glycoprotein and DENV RdRp domain, respectively. Our findings suggest that LFOB can inhibit DENV infection and might act as a potent prophylactic/therapeutic agent against DENV-2. In silico results suggested that ß-sitosterol and stigmasterol may block the viral entry by inhibiting the fusion process and viral replication respectively.

Evolution of the SARS-CoV-2 pandemic in India.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bat-derived betacoronavirus, that emerged around December 2019. In spite of the lesser genomic diversity of CoVs in general, a steady accumulation of mutations spread over its genome have been noted, resulting in the emergence of several clades and lineages. Majority of these mutations are random and non-functional changes; however a few variants of concern (VOC) and variants of interest (VOI) designated by the WHO since late 2020 have implications to diagnostics, pathogenicity and immune escape. This review discusses the various nomenclatures depicting the SARS-CoV-2 evolution, the designated VOCs and VOIs and the mutations characterizing these variants. The evolution of SARS-CoV-2 in India and the implications to vaccine efficacy and breakthrough infections is also addressed.

In vitro and in vivo studies reveal α-Mangostin, a xanthonoid from Garcinia mangostana, as a promising natural antiviral compound against chikungunya virus.

BACKGROUND: Chikungunya virus (CHIKV), a serious health problem in several tropical countries, is the causative agent of chikungunya fever. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. As diverse natural phenolic compounds have been shown to possess antiviral activities, we explored the antiviral activity of α-Mangostin, a xanthanoid, against CHIKV infection. METHODS: The in vitro prophylactic and therapeutic effects of α-Mangostin on CHIKV replication in Vero E6 cells were investigated by administering it under pre, post and cotreatment conditions. The antiviral activity was determined by foci forming unit assay, quantitative RT-PCR and cell-based immune-fluorescence assay. The molecular mechanism of inhibitory action was further proposed using in silico molecular docking studies. RESULTS: In vitro studies revealed that 8 µM α-Mangostin completely inhibited CHIKV infectivity under the cotreatment condition. CHIKV replication was also inhibited in virus-infected mice. This is the first in vivo study which clearly showed that α-Mangostin is effective in vivo by significantly reducing virus replication in serum and muscles. Molecular docking indicated that α-Mangostin can efficiently interact with the E2-E1 heterodimeric glycoprotein and the ADP-ribose binding cavity of the nsP3 macrodomain. CONCLUSIONS: The findings suggest that α-Mangostin can inhibit CHIKV infection and replication through possible interaction with multiple CHIKV target proteins and might act as a prophylactic/therapeutic agent against CHIKV.

Phylogenetic classification of the whole-genome sequences of SARS-CoV-2 from India & evolutionary trends.

BACKGROUND & OBJECTIVES: Several phylogenetic classification systems have been devised to trace the viral lineages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, inconsistency in the nomenclature limits uniformity in its epidemiological understanding. This study provides an integration of existing classifications and describes evolutionary trends of the SARS-CoV-2 strains circulating in India. METHODS: The whole genomes of 330 SARS-CoV-2 samples were sequenced using next-generation sequencing (NGS). Phylogenetic and sequence analysis of a total of 3014 Indian SARS-CoV-2 sequences from 20 different States/Union Territories (January to September 2020) from the Global Initiative on Sharing All Influenza Data (GISAID) database was performed to observe the clustering of Nextstrain and Phylogenetic Assignment of Named Global Outbreak LINeages (Pangolin) lineages with the GISAID clades. The identification of mutational sites under selection pressure was performed using Mixed Effects Model of Evolution and Single-Likelihood Ancestor Counting methods available in the Datamonkey server. RESULTS: Temporal data of the Indian SARS-CoV-2 genomes revealed that except for Uttarakhand, West Bengal and Haryana that showed the circulation of GISAID clade O even after July 2020, the rest of the States showed a complete switch to GR/GH clades. Pangolin lineages B.1.1.8 and B.1.113 identified within GR and GH clades, respectively, were noted to be indigenous evolutions. Sites identified to be under positive selection pressure within these clades were found to occur majorly in the non-structural proteins coded by ORF1a and ORF1b. INTERPRETATION & CONCLUSIONS: This study interpreted the geographical and temporal dominance of SARS-CoV-2 strains in India over a period of nine months based on the GISAID classification. An integration of the GISAID, Nextstrain and Pangolin classifications is also provided. The emergence of new lineages B.1.1.8 and B.1.113 was indicative of host-specific evolution of the SARS-CoV-2 strains in India. The hotspot mutations such as those driven by positive selection need to be further characterized.

In Vitro Antiviral Activity of α-Mangostin against Dengue Virus Serotype-2 (DENV-2).

Dengue virus (DENV), a member of the family Flaviviridae, is a threat for global health as it infects more than 100 million people yearly. Approved antiviral therapies or vaccines for the treatment or prevention of DENV infections are not available. In the present study, natural compounds were screened for their antiviral activity against DENV by in vitro cell line-based assay. α-Mangostin, a xanthanoid, was observed to exert antiviral activity against DENV-2 under pre-, co- and post-treatment testing conditions. The antiviral activity was determined by foci forming unit (FFU) assay, quantitative RT-PCR and cell-based immunofluorescence assay (IFA). A complete inhibition of DENV-2 was observed at 8 µM under the co-treatment condition. The possible inhibitory mechanism of α-Mangostin was also determined by docking studies. The molecular docking experiments indicate that α-Mangostin can interact with multiple DENV protein targets such as the NS5 methyltransferase, NS2B-NS3 protease and the glycoprotein E. The in vitro and in silico findings suggest that α-Mangostin possesses the ability to suppress DENV-2 production at different stages of its replication cycle and might act as a prophylactic/therapeutic agent against DENV-2.

Hospital admissions in children with developmental disabilities from ethnic minority backgrounds.

AIM: To compare hospital admission patterns after the first year of life in Australian children with developmental disabilities and children with no known disability, according to maternal country of birth and Indigenous status. METHOD: This was a retrospective cohort study using linked data across health, disability, and hospital admission databases. The study investigated 656 174 children born in Western Australia between 1983 and 2008 with a total of 1 091 834 records of hospital admissions. RESULTS: Children with no known disability born to Indigenous mothers had the highest rate of hospital admissions compared to children of non-Indigenous mothers. Children of foreign-born mothers from low-income countries had the highest rate of hospital admissions if disability was present. Children with cerebral palsy (CP) with or without associated intellectual disability had the highest rate of hospital admissions among children with developmental disability, especially if mothers were foreign-born. INTERPRETATION: Children with CP and intellectual disability, particularly from minority backgrounds (Indigenous Australian and foreign-born mothers), were at higher risk of being admitted to hospital after the first year of life. WHAT THIS PAPER ADDS: Hospital admissions in Australian children with and without disabilities differ according to maternal country of birth. Hospital admission rates in children without a developmental disability were greatest for Australian-born Indigenous children. Disabled Australian-born children of foreign-born mothers from low-income countries had the highest hospital admission rates. Hospital admission risk was greatest for Australian-born children with cerebral palsy, especially if mothers were foreign-born.

Perspectives for repurposing drugs for the coronavirus disease 2019.

The newly emerged 2019 novel coronavirus (CoV), named as severe acute respiratory syndrome CoV-2 (SARS-CoV-2), like SARS-CoV (now, SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV), has been associated with high infection rates with over 36,405 deaths. In the absence of approved marketed drugs against coronaviruses, the treatment and management of this novel CoV disease (COVID-19) worldwide is a challenge. Drug repurposing that has emerged as an effective drug discovery approach from earlier approved drugs could reduce the time and cost compared to de novo drug discovery. Direct virus-targeted antiviral agents target specific nucleic acid or proteins of the virus while host-based antivirals target either the host innate immune responses or the cellular machineries that are crucial for viral infection. Both the approaches necessarily interfere with viral pathogenesis. Here we summarize the present status of both virus-based and host-based drug repurposing perspectives for coronaviruses in general and the SARS-CoV-2 in particular.

Full-genome sequences of the first two SARS-CoV-2 viruses from India.

Background & objectives: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. Methods: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. Results: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. Interpretation & conclusions: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.

Use of professional interpreters for children and families with limited English proficiency: The intersection with quality and safety.

AIM: Linguistic diversity is increasing nationally; patients with limited English proficiency require provision of professional interpreters. We reviewed hospital-wide use of interpreters for low English proficiency in a tertiary hospital across emergency (ED), outpatient and inpatient presentations. METHODS: Two cohorts with low English proficiency presenting to Princess Margaret Hospital were audited. Records of new Refugee Health Service patients (presenting between January and July 2015) and non-Refugee Health Service low English proficiency patients (obtained through Language Services bookings) were reviewed to assess demographic profiles and use of interpreters for any occasion of service over the following 12 months (for each patient). RESULTS: Data from 188 patients were reviewed (Refugee Health Service: 119 patients; non-Refugee Health Service: 69 patients; total 1027 occasions of service); all were under 18 years of age. High socio-economic disadvantage and limited education was noted. Almost all (98.5%) had low English proficiency; 3 Refugee Health Service parents spoke English; 68% of non-Refugee Health Service patients were in families previously transitioned from that service. Interpreter use was poor across all areas. Thirty-four patients had 46 inpatient admissions with documented interpreter use for 59% (20/34) of these. All patients underwent at least one procedure, with no instances of interpreter documentation for procedure consent. Documented interpreter use was minimal in outpatient occasions of service (32/118, 27% Refugee Health Service; 18/222, 8% non-Refugee Health Service). Only one Refugee Health Service patient had evidence of ED interpreter use, out of 78 ED occasions of service (34 patients). CONCLUSIONS: Despite documented low English proficiency, suboptimal and inadequate use of professional interpreters persists. Low English proficiency patients are vulnerable, with socio-economic disadvantage, likely to impact on health outcomes and compliance. Organisational risk also is highlighted, including impact on clinical handover, informed consent and non-compliance with state language services policy. Further staff education and quality improvement work is essential.

Whole-genome-based characterization of three human Rotavirus C strains isolated from gastroenteritis outbreaks in Western India and a provisional intra-genotypic lineage classification system.

The number of whole-genome sequences of human rotavirus C (RVC) strains available in public databases is recently increasing. Thus far from India only a single whole genome of human RVC of a sporadic case was available. In this study, nearly full-length genome sequencing and phylogenetic analyses of three RVC strains isolated from three different gastroenteritis outbreaks during 2010-2014 in Western India was carried out. Further, an intra-genotypic lineage classification system for human RVCs based on the nucleotide divergence cut-off values was proposed by using the algorithm of the Rotavirus Classification Working Group. Two lineages could be defined for all the genes except the VP7 gene and the M3 VP3 genotype. Provisional classification of the lineages indicated the absence of reassortment events in the genomic constellation of Indian strains, contrary to earlier reports. The comparatively higher variability of the NSP1, NSP3, NSP5 and M2 VP3 genotype, emphasizes their utility in lineage classification.

Risk of Developmental Disorders in Children of Immigrant Mothers: A Population-Based Data Linkage Evaluation.

OBJECTIVES: To evaluate the prevalence and risks of developmental disability (autism spectrum disorder, intellectual disability, and cerebral palsy) in Western Australian children of different groups of foreign-born women. STUDY DESIGN: Western Australian population-based linked data of 764 749 singleton live births from 1980 to 2010 were used to compare disability outcomes among children of foreign-born, Australian-born non-Indigenous, and Indigenous women. The risk of disability was assessed using multinomial logistic regression. RESULTS: Overall, the prevalence of any disability was lowest for the children of foreign-born mothers. From 1980 to 1996 but not from 1997 to 2010, children born to mothers from foreign-born low-income countries had an increased relative risk of autism spectrum disorder with intellectual disability, and children born to foreign-born mothers from upper-middle-income countries had an increased risk of cerebral palsy with intellectual disability. After adjusting for smoking, the relative risks of intellectual disability and cerebral palsy with intellectual disability were markedly decreased in children of Australian-born Indigenous mothers. CONCLUSIONS: Although we did not find among children born to foreign-born women an increased prevalence across all the measured developmental outcomes, we did observe an increased risk of autism spectrum disorder with intellectual disability and cerebral palsy with intellectual disability for mothers of some foreign-born groups. Our findings related to smoking in the Indigenous population underscore its possible role on the causal pathway to intellectual disability. Maternal migration is considered a factor on the causal pathway to intellectual disability. Maternal migration may be either a risk or a protective factor on the causal pathway to developmental disabilities and the direct role of migration is inconclusive in our study.

Are preterm birth and intra-uterine growth restriction more common in Western Australian children of immigrant backgrounds? A population based data linkage study.

BACKGROUND: To compare the prevalence of preterm birth, post term birth, intra-uterine growth restriction and distribution of Apgar scores in offspring of foreign-born women in Western Australia with that of their Australian-born non-Indigenous and Indigenous counterparts. METHODS: A population-based linked data study, involving 767,623 singleton births in Western Australia between 1980 and 2010 was undertaken. Neonatal outcomes included preterm birth, post term births, intra-uterine growth restriction (assessed using the proportion of optimal birth weight) and low Apgar scores. These were compared amongst foreign-born women from low, lower-middle, upper middle and high income countries and Australian-born non-Indigenous and Indigenous women over two different time periods using multinomial logistic regression adjusted for covariates. RESULTS: Compared with Australian born non-Indigenous women, foreign-born women from low income countries were at some increased risk of extreme preterm (aRRR 1.59, 95% CI 0.87, 2.89) and very early preterm (aRRR 1.63, 95% CI 0.92, 2.89) births during the period from 1980 to 1996. During the period from 1997 to 2010 they were also at some risk of extreme preterm (aRRR 1.42, 95% CI 0.98, 2.04) very early preterm (aRRR 1.34, 95% CI 1.11, 1.62) and post term birth (aRRR 1.93, 95% CI 0.99, 3.78). During this second time period, other adverse outcomes for children of foreign-born women from low income and middle income countries included increases in severe (aRRR 1.69, 95% CI 1.30, 2.20; aRRR 1.72, 95% CI 1.53, 1.93), moderate (aRRR 1.54, 95% CI 1.32, 1.81; aRRR 1.59, 95% CI 1.48, 1.70) and mild (aRRR 1.28, 95% CI 1.14, 1.43; aRRR 1.31, 95% CI 1.25, 1.38) IUGR compared to children of Australian-born non-Indigenous mothers. Uniformly higher risks of adverse outcomes were also demonstrated for infants of Indigenous mothers. CONCLUSIONS: Our findings illustrate the vulnerabilities of children born to foreign women from low and middle-income countries. The need for exploratory research examining mechanisms contributing to poorer birth outcomes following resettlement in a developed nation is highlighted. There is also a need to develop targeted interventions to improve outcomes for these women and their families.

Paediatric asylum seekers in Western Australia: Identification of adversity and complex needs through comprehensive refugee health assessment.

AIM: Asylum seekers (ASs) report high rates of trauma and difficulty accessing health and educational services. This study aims to ascertain the needs of paediatric ASs managed by the tertiary Western Australian paediatric Refugee Health Service (RHS), including demographic features, the range of health and psychosocial issues and ongoing management challenges. METHODS: An audit of multidisciplinary RHS assessments, health records and hospital admissions for new AS patients (<16 years) between July 2012 and June 2016 was undertaken. RESULTS: Records for 110 ASs were reviewed (mean age 6 years, standard deviation 4.72 years). Multiple issues (medical, psychological, developmental, educational) were identified after the first tertiary assessment (median 4, interquartile range (IQR) 3-6) compared to referral sources (median 1, IQR 0-2, P < 0.001). The median number of issues per child at audit completion was 6 (IQR 4-7, P < 0.001). Multiple refugee adverse childhood experiences were identified, with all experiencing >3 (median 4, IQR 4-5). Most had detention experience (107/110, 97.2%), family separation (91/108, 84%) and interrupted education (41/46, 89.2%). The median duration of detention was 7 months (IQR 3-12.5 months) at time of initial review across multiple sites (median 2, IQR 1-3 locations). High rates of hospital interaction were evident, with 45.4% requiring hospital admission and 36% presenting to the emergency department. The median number of outpatient appointments attended per child was 5 (IQR 2-8). Parental and child mental health concerns were identified in 53.6 and 46.3%, respectively. CONCLUSIONS: Paediatric ASs have complex trauma backgrounds with exposure to multiple adverse events within disrupted family units. The majority of Western Australian ASs assessed demonstrated negative health or education sequelae compounded by detention not previously identified prior to comprehensive paediatric review. Our data support the urgent removal of ASs from held detention. Ongoing holistic assessment and management engaging multidisciplinary trauma-informed paediatric refugee services to optimise health and well-being is recommended.

Complexities of conducting research in adolescent refugees resettling in Australia.

Adolescent refugees resettling in Australia are a vulnerable and marginalised population. Dedicated research to help better understand their health-care needs remains scarce. There are multiple complexities which may deter health professionals from conducting research with this population. Health-care system barriers, such as lack of adolescent- and refugee-specific health-care services, complicate comprehensive data collection. Limited investigator knowledge pertaining to culturally appropriate research in a population with limited English proficiency or a history of trauma can have an impact on adolescent participation and retention in research studies. Additional ethical and legal issues relating to adolescent consent and confidentiality, which include suicidality and physical or sexual abuse, can arise during research and cause potential harm to adolescents if not managed appropriately. This article highlights current knowledge and understanding relating to these issues along with recommendations to address barriers and safeguard adolescents, with the aim of promoting high-quality research that will benefit resettling adolescent refugees.