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Background Pregnancy and early infancy are increased risk periods for severe adverse effects of respiratory infections. Aboriginal and/or Torres Strait Islander (respectfully referred to as First Nations) women and children in Australia bear a disproportionately higher burden of respiratory diseases compared to non-Indigenous women and infants. Influenza vaccines and whooping cough (pertussis) vaccines are recommended and free in every Australian pregnancy to combat these infections. We aimed to assess the equity of influenza and/or pertussis vaccination in pregnancy for three priority groups in Australia: First Nations women; women from culturally and linguistically diverse (CALD) backgrounds; and women living in remote areas or socio-economic disadvantage. Methods We conducted individual record linkage of Perinatal Data Collections with immunisation registers/databases between 2012 and 2017. Analysis included generalised linear mixed model, log-binomial regression with a random intercept for the unique maternal identifier to account for clustering, presented as prevalence ratios (PR) and 95% compatibility intervals (95%CI). Results There were 445,590 individual women in the final cohort. Compared with other Australian women (n = 322,848), First Nations women (n = 29,181) were less likely to have received both recommended antenatal vaccines (PR 0.69, 95% CI 0.67–0.71) whereas women from CALD backgrounds (n = 93,561) were more likely to have (PR 1.16, 95% CI 1.10–1.13). Women living in remote areas were less likely to have received both vaccines (PR 0.75, 95% CI 0.72–0.78), and women living in the highest areas of advantage were more likely to have received both vaccines (PR 1.44, 95% CI 1.40–1.48). Conclusions Compared to other groups, First Nations Australian families, those living in remote areas and/or families from lower socio-economic backgrounds did not receive recommended vaccinations during pregnancy that are the benchmark of equitable healthcare. Addressing these barriers must remain a core priority for Australian health care systems and vaccine providers. An extension of this cohort is necessary to reassess these study findings.

Recent surveys identified trachomatous inflammation - follicular (TF) at endemic levels in the Torres Strait Islands; however, local health staff do not report trachomatous trichiasis (TT) in adults. We undertook a cross-sectional survey involving eye examination and microbiological testing to better understand this disconnect.We examined 169 of 207 (82%) residents and collected ocular swabs for polymerase chain reaction (PCR) testing for Chlamydia trachomatis. Other viral PCR tests and bacterial culture were also performed.TF prevalence in children aged 5-9 years was 23% (7/30). No ocular C. trachomatis was identified by PCR. For the 72 participants (43%) with follicles, bacterial culture was positive for 11 (15%) individuals. No individual had trachomatous trichiasis.Follicular conjunctivitis consistent with TF was prevalent but ocular C. trachomatis and cicatricial trachoma were absent. Non-chlamydial infections or environmental causes of follicular conjunctivitis may be causing TF in this community.In similar settings, reliance on simplified clinical assessment alone may lead to an overestimation of the public health problem posed by trachoma. Consideration should be given to incorporating C. trachomatis PCR, and in certain settings, a detailed clinical exam could be performed by an experienced ophthalmologist during prevalence surveys.

IntroductionChildren in low-mid income countries, and First Nations children in high-income countries, experience disproportionately high rates of Streptococcus pneumoniae and Haemophilus influenzae infections and diseases including pneumonia and otitis media. We previously observed that infants from Papua New Guinea had no evidence of waning maternal immunity for H. influenzae-specific antibodies. In this study, we assessed S. pneumoniae and H. influenzae antibody titres in Australian First Nation mothers and infants to determine antigen-specific antibody ontogenies and whether H. influenzae antibody titres in infants were due to low maternal antibody titres or lack of placental transfer.MethodsBreast milk, infant nasopharyngeal swabs and ear assessment data were collected 1-, 2-, 7-months post-birth as well as maternal, cord and 7-month-old infant sera, from 85 Australian Aboriginal and Torres Strait Islander mother-infant pairs. Serum IgG and breast milk IgG and IgA antibody titres to S. pneumoniae antigens (PspA1, PspA2, CbpA, Ply) and H. influenzae antigens (PD, ChimV4, OMP26, rsPilA) were measured.ResultsIgG titres in maternal and cord sera were similar for all antigens, except Ply (higher in cord; p=0.004). Sera IgG titres at 7-months of age were lower than cord sera IgG titres for all S. pneumoniae antigens (pH. influenzae PD (p=0.029), similar for OMP26 (p=0.817) and rsPilA (p=0.290), and lower for ChimV4 (p=0.004). Breast milk titres were similar for all antigens at 1, 2 and 7-months except OMP26 IgA (lower at 7-months than 1-month; p=0.035), PspA2 IgG (p=0.012) and Ply IgG that increased by 7-months (p=0.032). One third of infants carried nontypeable Haemophilus influenzae (NTHi), 45% carried S. pneumoniae and 52% had otitis media (OM) observed at least once over the 7-months. 73% of infants who carried either S. pneumoniae or NTHi, also had otitis media observed.ConclusionsSimilarities between maternal and cord IgG titres, and absence of waning, support a lack of maternal H. influenzae IgG antibodies available for cross-placental transfer. Increased maternal anti-PD IgG could offer some protection from early carriage with NTHi, and maternal immunisation strategies should be considered for passive-active immunisation of infants to protect against S. pneumoniae and H. influenzae diseases.Trial registrationClinicalTrials.gov NCT00714064 and NCT00310349.

Background Strongyloides stercoralis is a soil-transmitted helminth, endemic in remote Aboriginal and Torres Strait Islander communities in northern Australia with estimates of prevalences up to 60%. Hyperinfection in the setting of immunosuppression is a rare but well-recognised cause of significant morbidity and mortality. However, the morbidity associated with chronic uncomplicated infection is less well characterised. Methods This retrospective case-control study measured the prevalence of symptoms potentially attributable to S. stercoralis infection and their association with seropositivity. Records of primary healthcare presentations were reviewed for symptoms in the 12 months before and after an ivermectin mass drug administration (MDA) in a remote Aboriginal community. Results One hundred and seventy-five S. stercoralis seropositive cases were matched with 175 seronegative controls. The most frequently reported symptom overall in the 12 months prior to the MDA was cough followed by abdominal pain, weight loss/malnutrition, diarrhoea and pruritis. Seropositive cases were not more likely than matched controls to have symptoms typically attributed to strongyloidiasis. In the seropositive cohort, we found no difference in symptoms in the 12 months before and after an ivermectin MDA despite a reduction in seroprevalence. Conclusion We found no evidence to suggest that S. stercoralis seropositivity was associated with increased symptoms when compared to matched seronegative controls. Treatment with ivermectin did not reduce symptoms in seropositive cases. Without evidence to support that population-based screening or treatment programs reduce symptoms, the emphasis must remain on identifying and managing those few individuals with immunosuppression that predisposes them to potentially life-threatening hyperinfection. This article is protected by copyright. All rights reserved.

Children in low-mid income countries, and First Nations children in high-income countries, experience disproportionately high rates ofBreast milk, infant nasopharyngeal swabs and ear assessment data were collected 1-, 2-, 7-months post-birth as well as maternal, cord and 7-month-old infant sera, from 85 Australian Aboriginal and Torres Strait Islander mother-infant pairs. Serum IgG and breast milk IgG and IgA antibody titres toIgG titres in maternal and cord sera were similar for all antigens, except Ply (higher in cord; p=0.004). Sera IgG titres at 7-months of age were lower than cord sera IgG titres for allSimilarities between maternal and cord IgG titres, and absence of waning, support a lack of maternalClinicalTrials.gov NCT00714064 and NCT00310349.

Background Following high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to Methods A matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VEadj) for sex and First Nations status. Results There were 1,125 cases and 10,645 matched controls analysed. Overall VEadj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41–60). VEadj was 60% (95% CI 46–70) for children who received two doses in 2018, and 60% (95% CI 48–69) for children vaccinated appropriately according to schedule completeness. VE increased with age. Conclusions Moderate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.

To identify maternal and perinatal risk factors associated with childhood anaemia. A retrospective cohort study was conducted in three remote Katherine East Aboriginal communities in Northern Territory, Australia. Children born 2004–2014 in Community A and 2010–2014 in Community B and C, and their respective mothers were recruited into the study. Maternal and child data were linked to provide a longitudinal view of each child for the first 1000 days from conception to 2-years of age. Descriptive analyses were used to calculate mean maternal age, and proportions were used to describe other antenatal and perinatal characteristics of the mother/child dyads. The main outcome was the prevalence of maternal anaemia in pregnancy and risk factors associated with childhood anaemia at age 6 months. Prevalence of maternal anaemia in pregnancy was higher in the third trimester (62%) compared to the first (46%) and second trimesters (48%). There was a strong positive linear association (R2 = 0.46, p

A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV-AR strain and its association with severe HPeV infections.HPeV3-positive samples collected from hospitalized infants aged 5-252 days in two Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific PCR was designed and utilized to screen all clinical and community HPeV3-positive samples.Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the non-structural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed most (75%) hospitalized HPeV3 cases involved the AR strain in the first three clinical outbreaks, with declining prevalence in the 2019-20 season. The AR strain was not statistically associated with increased clinical severity amongst hospitalised infants.The HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.

Antenatal inactivated influenza (IIV) and pertussis-containing vaccines (dTpa) offer protection against severe respiratory infections for pregnant women and infants6 months of age. Both vaccines are recommended in pregnancy; however, little is known about temporal or jurisdictional trends and predictors of uptake.To identify gaps and predictors of IIV and/or dTpa vaccinations in Australian pregnancies from 2012 to 2017.We conducted a probabilistically linked, multi-jurisdictional population-based cohort study, drawing from perinatal data collections and immunisation databases. We used a generalised linear mixed model with a random effect term to account for clustering of multiple pregnancies within mothers, to calculate vaccination uptake, and identify predictors of uptake by maternal demographic, pregnancy, and health characteristics.Of 591 868 unique pregnancies, IIV uptake was 15%, dTpa 27% and 12% received both vaccines. Pertussis vaccinations in First Nations pregnancies were 20% lower than non-Indigenous pregnancies; dTpa was strongly associated with IIV uptake (risk ratio (RR): 8.60, 95% CI 8.48-8.73). This trend was temporally and jurisdictionally consistent. First Nations women were more likely to have had IIV in pregnancy before the introduction of dTpa in the pregnancy program: (RR: 1.48, 95% CI 1.40-1.57), but less likely after dTpa implementation (RR: 0.78, 95% CI 0.76-0.80).Inequity in vaccine uptake between First Nations and non-Indigenous pregnancies, and dismal rates of vaccination in pregnancy overall need urgent review, particularly before the next influenza pandemic or pertussis outbreak. If antenatal dTpa is driving IIV uptake, changes in antenatal healthcare practices are needed to ensure vaccines are offered equitably and optimally to protect against infection.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection hospitalisations in Aboriginal infants specifically those aged

BackgroundThere is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCV) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among under-vaccinated Australian children.MethodsBirth and vaccination records, IPD notifications and hospitalisations were individually linked for children aged < five years, born between 2001 and 2012 in two Australian states (New South Wales and Western Australia; 1.37 million children). Using Poisson regression models, we examined the association between PCV coverage, in small geographical units, and the incidence of (1) 7-valent PCV (PCV7)-type IPD, (2) all-cause pneumonia and (3) pneumococcal and lobar pneumonia hospitalisation in under-vaccinated children. Under-vaccinated children received < two doses of PCV at < 12 months of age and no doses at ≥ 12 months of age. Potential confounding variables were selected for adjustment a priori with the assistance of a directed acyclic graph. The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on addressed at birth only) and unmeasured confounders.FindingsThere were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% CI 0.958-0.975, p-value ConclusionsIn this study we observed substantial indirect protection at low PCV coverage, challenging assumptions high vaccine coverage is required.Author summaryWhy was this study done?Pneumococcal conjugate vaccines (PCVs) reduce the burden of pneumococcal disease in vaccinated and unvaccinated populations through both direct and indirect (herd) effects.The indirect effects comprise a substantial component of overall vaccine impact, contributing to the cost-effectiveness of the vaccine but little is known about what factors contribute to herd protection, including vaccination coverage.In this study, we examined association between PCV coverage and indirect effects within in diverse populations within AustraliaWhat did the researchers do and find?Using a large dataset of 1.3 million children from two states in Australia, we quantified the relationship between PCV coverage within small geographical units and indirect protection against pneumococcal disease. We also performed similar analyses for infants too young to be fully vaccinated, urban, rural and Indigenous populations.There were strong inverse relationships between PCV coverage and the incidence of severe invasive disease due to vaccine types and pneumonia hospitalisations among under-vaccinated children i.e. higher coverage were associated with greater reductions in disease due to indirect effects. We also found substantial indirect effects at relatively low levels of PCV coverage. We estimated that 50% and 90% coverage of 7-valent PCV (PCV7) among children under five years of age prevented almost three-quarters (72.5%, 95% CI 51.6-84.4) and almost all (95.2%, 95% CI 89.4-97.8) of PCV7-type severe invasive disease, respectively. For pneumonia, we estimated that 50% and 90% coverage was sufficient to prevent one-third (33.3%, 95% CI 27.3-38.8) and about half (51.7%, 95% CI 43.7-58.6) of all-cause pneumonia hospitalisations among under-vaccinated children.These trends were similar for children less than four months old, urban, rural and Indigenous populations, although these effects were smaller for rural and Indigenous populations. There was also a trend towards decreasing incidence of PCV13-type IPD among under-vaccinated children as PCV13 coverage increased.What do these findings mean?Our results challenge existing assumptions that high PCV coverage is required to achieve substantial indirect protection.Understanding the determinants of indirect effects are particularly urgent as countries that have controlled vaccine-type pneumococcal disease consider using reducing the number of PCV doses (from three to two). Reduced dose schedules have the potential to significantly lower program costs while maintaining vaccine impact, providing indirect protection is achieved and preserved.

OBJECTIVES To assess the extent to which the 2018-19 New South Wales summer influenza epidemic was associated with overseas or domestic travel and with seasonal influenza vaccination status. DESIGN, SETTING Unmatched case-control study, based on an online survey distributed from the NSW Notifiable Conditions Information Management System (NCIMS) to people for whom mobile phone numbers were available. PARTICIPANTS A case was defined as a person with notified laboratory-confirmed influenza with onset of illness between 1 December 2018 and 21 March 2019. People with notified pertussis infections (confirmed or probable) were selected as controls. MAIN OUTCOME MEASURES Notified influenza infection, by travel and contact with unwell overseas travellers in the week before onset of illness and seasonal influenza vaccination status (as the primary exposures). RESULTS Valid survey responses were provided by 648 of 2806 invited people with notified influenza (23%) and 257 of 796 invited people with notified pertussis (32%). The demographic characteristics of the respondents were similar to those of the source population (7251 cases, 2254 controls). During the first two months of the summer of 2018-19, notified influenza was more likely for people who had travelled overseas or had contact with an ill overseas traveller in the week before symptom onset (adjusted OR [aOR], 6.99; 95% CI, 3.59-13.6), but not during the second two months (aOR, 1.63; 95% CI, 0.79-3.35). Influenza vaccination status was not associated with the likelihood of notified influenza. CONCLUSIONS Travel-related factors were early drivers of the 2018-19 NSW summer influenza epidemic; local transmission sustained the outbreak despite unfavourable conditions later in summer. Our findings prompted re-evaluation of recommendations for pre-travel vaccination in NSW. The role of travel in out-of-season influenza outbreaks should be considered in other temperate zones.

Background: Pregnant women and infants

Water, sanitation and hygiene interventions have been advocated as important complements to deworming programs to improve soil-transmitted helminth control. Evidence for the impact of water, sanitation and hygiene on soil-transmitted helminth infections is mixed, and based mainly on cross-sectional studies. In this study, we assessed associations between individual- and household-level water, sanitation and hygiene variables and soil-transmitted helminth infections, using data collected during the 2 year follow-up study period of the WASH for WORMS randomised controlled trial in Timor-Leste. Data were collected across four surveys, conducted at 6 monthly intervals in 23 communities. We analysed water, sanitation and hygiene and sociodemographic variables as risk factors for infection with Necator americanus, Ascaris spp., and undifferentiated soil-transmitted helminth infection, using generalised linear mixed models to account for clustering at community, household and participant levels. Water, sanitation and hygiene risk factors were examined both concurrently and with a 6 month lag period that coincided with the most recent deworming. The analysis included 2333 participants. Factors associated with N. americanus infection included age group, male sex (adjusted odds ratio (aOR) 3.1, 95% confidence interval (CI) 2.4–4.2), working as a farmer (aOR 1.7, 95% CI 1.2–2.4), and completing secondary school or higher (aOR 0.29, 95% CI 0.16–0.53). Risk factors for Ascaris spp. infection included age group, living in a dwelling with more than six people (aOR 1.6, 95% CI 1.1–2.3), having a tube well or borehole as the household water source (aOR 3.7, 95% CI 1.3–10.8), and using a latrine shared between households 6 months previously (aOR 2.3, 95% CI 1.2–4.3). Handwashing before eating was protective against infection with any soil-transmitted helminth (aOR 0.79, 95% CI 0.65–0.95). In the context of regular deworming, few water, sanitation and hygiene-related factors were associated with soil-transmitted helminth infections. Future research examining the role of water, sanitation and hygiene in soil-transmitted helminth transmission is required, particularly in low transmission settings after cessation of deworming. Identifying improved indicators for measuring water, sanitation and hygiene behaviours is also a key priority.

Water, sanitation, and hygiene (WASH) interventions have been proposed as an important complement to deworming programs for sustainable control of soil-transmitted helminth (STH) infections. We aimed to determine whether a community-based WASH program had additional benefits in reducing STH infections compared with community deworming alone. We conducted the WASH for WORMS cluster-randomized controlled trial in 18 rural communities in Timor-Leste. Intervention communities received a WASH intervention that provided access to an improved water source, promoted improved household sanitation, and encouraged handwashing with soap. All eligible community members in intervention and control arms received albendazole every 6 months for 2 years. The primary outcomes were infection with each STH, measured using multiplex real-time quantitative polymerase chain reaction. We compared outcomes between study arms using generalized linear mixed models, accounting for clustering at community, household, and individual levels. At study completion, the integrated WASH and deworming intervention did not have an effect on infection with Ascaris spp. (relative risk [RR] 2.87, 95% confidence interval [CI]: 0.66–12.48, P = 0.159) or Necator americanus (RR 0.99, 95% CI: 0.52–1.89, P = 0.987), compared with deworming alone. At the last follow-up, open defecation was practiced by 66.1% (95% CI: 54.2–80.2) of respondents in the control arm versus 40.2% (95% CI: 25.3–52.6) of respondents in the intervention arm (P = 0.005). We found no evidence that the WASH intervention resulted in additional reductions in STH infections beyond that achieved with deworming alone over the 2-year trial period. The role of WASH on STH infections over a longer period of time and in the absence of deworming remains to be determined.

Objectives: N. meningitidis carriage in Australia is poorly understood. This study aimed to estimate prevalence and risk factors for carriage of N. meningitidis in South Australian university students. We also sought to identify whether delayed freezing of oropharyngeal samples altered PCR positivity, cycle threshold, or culture positivity. Methods: Oropharyngeal swabs were taken from first year university students and repeated after 3 months, with risk factor questionnaires completed at both visits. Specimens were subjected to real-time PCR screening for the presence of specific meningococcal DNA. Results: The study enrolled 421 individuals, 259 returned at 3 months. At baseline, 56% of participants were female and 1.9% smokers. Carriage of N. meningitidis at baseline was 6.2% (95% CI, [4.2%, 8.9%]). Visiting a bar more than once a week (OR 9.07; [2.44, 33.72]) and intimate kissing (OR 4.37; [1.45, 13.14]) were associated with increased carriage. After imputing missing data, the point estimate for carriage at 3 months was 8.6% compared to 6.2% at baseline (OR 1.42; 0.91 to 2.20). Recovery of N. meningitidis on selective agar was significantly reduced in cryovials frozen at 48 hours compared to 6 hours (24/26, 92.3% vs. 14/26, 53.9%, p = 0.002). Conclusion: Attending bars and engaging in intimate kissing is associated with oropharyngeal carriage in South Australian university students. Adolescent meningococcal vaccine programs should be implemented at school, prior to increased attendance at bars, intimate contact, and carriage acquisition. Delaying freezing of oropharyngeal specimens longer than 16 hours reduces yield of N. meningitidis by culture but not PCR detection.

Objective: Ascertain predictors of inactivated influenza vaccine (IIV) uptake in pregnancy in mother–infant pairs from six Australian sites over four consecutive influenza seasons (2012–2015). Methods: Prospective observational cohort study calculating proportions of unvaccinated and vaccinated pregnancies. Multivariable logistic regression calculating adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) to determine demographic, pregnancy and birth characteristics as predictors of IIV uptake in pregnancy. Results: Uptake of IIV was 36% (n=3,651/9,878) with only 3–4% during the first trimester. Validation of IIV receipt was obtained for 77% of vaccinated participants. Predictors of IIV uptake in pregnancy were: healthcare provider recommendation to have IIV during pregnancy (aOR 7.04 [95%CI 5.83‐8.50]): GP (aOR 4.12 [95%CI 3.43‐4.98]), obstetrician (aOR 4.41 [95%CI 3.45‐5.64]), midwife (aOR 1.88 [95%CI 1.51‐2.36]); previous IIV within 12 months of their current pregnancy (aOR 2.87 [95%CI 2.36‐3.50]); and pertussis vaccination during the current pregnancy (aOR 4.88 [95%CI 4.08‐5.83]). Conclusions and implications for public health: Healthcare provider discussions with pregnant women about the risks associated with influenza infection during pregnancy and early infancy and evidence about the safety and effectiveness of IIV are required. Recommending and offering IIV in pregnancy needs to be included in these discussions to improve uptake.

Pacific Island countries have a high burden of scabies and impetigo. Understanding of the epidemiology of these diseases is needed to target public health interventions such as mass drug administration (MDA). The aim of this study is to determine the prevalence of scabies and impetigo in Solomon Islands as well as the relationship between them and their distribution. We conducted a prevalence study in 20 villages in Western Province in Solomon Islands. All residents of the village were eligible to participate. Nurses conducted clinical assessments including history features and skin examination. Diagnosis of scabies was made using the 2020 International Alliance for the Control of Scabies diagnostic criteria. Assessments were completed on 5239 participants across 20 villages. Overall scabies prevalence was 15.0% (95%CI 11.8–19.1). There was considerable variation by village with a range of 3.3% to 42.6%. There was a higher prevalence of scabies in males (16.7%) than females (13.5%, adjusted relative risk 1.2, 95%CI 1.1–1.4). Children aged under two years had the highest prevalence (27%). Overall impetigo prevalence was 5.6% (95%CI 4.2–7.3), ranging from 1.4% to 19% by village. The population attributable risk of impetigo associated with scabies was 16.1% (95% CI 9.8–22.4). The prevalence of scabies in our study is comparable to previous studies in Solomon Islands, highlighting a persistent high burden of disease in the country, and the need for public health strategies for disease control., Author summary Scabies is a skin disease caused by infestation with the mite Sarcoptes scabiei var. hominis. The mite burrows under the skin causing intense itch. Scabies lesions are commonly infected with bacteria, causing impetigo. Pacific Island countries have a high burden of scabies due to overcrowding, the tropical environment and limited access to treatment. We aimed to assess the prevalence of scabies and impetigo in 20 villages in Western Province of Solomon Islands. We used the International Alliance for the Control of Scabies 2020 diagnostic criteria to diagnoses scabies. We found that 15% of the 5239 people surveyed had scabies, and 5.6% had impetigo. While the prevalence of scabies was comparable to other studies there were fewer cases of impetigo than observed previously. The burden of disease was highest among children. Mass drug administration, where the whole community is given treatment for a condition regardless of whether they have symptoms of the disease, has been shown to reduce the prevalence of scabies. This study supports the need for mass drug administration for scabies in Solomon Islands.

Background Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, leads to significant morbidity and mortality worldwide. This review aimed to establish the effectiveness of meningococcal vaccines at preventing IMD and N. meningitidis pharyngeal carriage. Methods A search within PubMed, Embase, Scopus, and unpublished studies up to 1 February 2020 was conducted. Results After removal of duplicates, 8565 studies were screened and 27 studies included. Protection was provided by meningococcal C vaccines for group C IMD (odds ratio [OR], 0.13 [95% confidence interval {CI}, .07–.23]), outer membrane vesicle (OMV) vaccines against group B IMD (OR, 0.35 [95% CI, .25–.48]), and meningococcal A, C, W, Y (MenACWY) vaccines against group ACWY IMD (OR, 0.31 [95% CI, .20–.49]). A single time series analysis found a reduction following an infant 4CMenB program (incidence rate ratio, 0.25 [95% CI, .19–.36]). Multivalent MenACWY vaccines did not reduce carriage (relative risk [RR], 0.88 [95% CI, .66–1.18]), unlike monovalent C vaccines (RR, 0.50 [95% CI, .26–.97]). 4CMenB vaccine had no effect on group B carriage (RR, 1.12 [95% CI, .90–1.40]). There was also no reduction in group B carriage following MenB-FHbp vaccination (RR, 0.98 [95% CI, .53–1.79]). Conclusions Meningococcal conjugate C, ACWY, and OMV vaccines are effective at reducing IMD. A small number of studies demonstrate that monovalent C conjugate vaccines reduce pharyngeal N. meningitidis carriage. There is no evidence of carriage reduction for multivalent MenACWY, OMV, or recombinant MenB vaccines, which has implications for immunization strategies. Clinical Trials Registration CRD42018082085 (PROSPERO).

Combined hepatitis A and typhoid vaccine is available in Australia, but licensed for use from age 16 years; however it is used “off-label” in children. The combined vaccine is well tolerated in children aged 2–16 years and the risk of adverse events is similar to those receiving concurrent monovalent vaccines.

Background Higher density of Neisseria meningitidis carriage may be associated with transmission of the meningococcus. Our aim was to establish the impact of meningococcal B (4CMenB) vaccine on N. meningitidis carriage density. Methods We compared 4CMenB vaccine to control among 913 South Australian students aged approximately 15–18 years in a cluster randomized trial who had N. meningitidis carriage at 12 months. Oropharyngeal swabs were collected at baseline and 12 months later to detect N. meningitidis carriage. Colony-forming units per milliliter (CFU/mL) were estimated by generating a standard curve that plotted quantitative polymerase chain reaction cycle threshold values against log-normalized CFU. Results Among the 913 students with N. meningitidis carriage at 12 months, there was no difference in mean carriage density between the vaccinated (n = 434; 3.80 log CFU/mL [standard deviation {SD}, 1.29]) and control group (n = 479; 3.73 log CFU/mL [SD, 1.30]; P = .51). Higher N. meningitidis carriage density at baseline was associated with an increase in the odds of persistent carriage at 12 months (n = 504; odds ratio [OR] per 1.0 log CFU/mL increase in density, 1.36 [95% confidence interval {CI}, 1.17–1.58]; P Conclusions 4CMenB vaccine did not reduce carriage density of N. meningitidis 12 months postvaccination, despite increased carriage clearance. Higher carriage density is likely to enable transmission through prolonged periods of population exposure. Clinical Trials Registration NCT03089086.

Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group AStreptococcus(GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan–Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.

Objectives To describe trends in the age-specific incidence of serogroup B invasive meningococcal disease (IMD) in Australia, 1999-2015. Design, setting, participants Analysis in February 2017 of de-identified notification data from the Australian National Notifiable Diseases Surveillance System of all notifications of IMD in Australia with a recorded diagnosis date during 1999-2015.Major outcomes: IMD notification rates in Australia, 1999-2015, by age, serogroup, Indigenous status, and region. Results The incidence of meningococcal serogroup B (MenB) disease declined progressively from 1.52 cases per 100 000 population in 2001 to 0.47 per 100 000 in 2015. During 2006-2015, MenB accounted for 81% of IMD cases with a known serogroup; its highest incidence was among infants under 12 months of age (11.1 [95% CI, 9.81-12.2] per 100 000), children aged 1-4 years (2.82 [95% CI, 2.52-3.15] per 100 000), and adolescents aged 15-19 years (2.40 [95% CI, 2.16-2.67] per 100 000). Among the 473 infants under 2 years of age with MenB, 43% were under 7 months and 69% under 12 months of age. The incidence of meningococcal serogroup C (MenC) disease prior to the introduction of the MenC vaccine in 2003 was much lower in infants than for MenB (2.60 cases per 100 000), the rate peaking in people aged 15-19 years (3.32 per 100 000); the overall case fatality rate was also higher (MenC, 8%; MenB, 4%). The incidence of MenB disease was significantly higher among Indigenous than non-Indigenous Australians during 2006-2015 (incidence rate ratio [IRR], 3.8; 95% CI, 3.3-4.5). Conclusions Based on disease incidence at its current low endemic levels, priority at risk age/population groups for MenB vaccination include all children between 2 months and 5 years of age, Indigenous children under 10 years of age, and all adolescents aged 15-19 years. Given marked variation in meningococcal disease trends over time, close scrutiny of current epidemiologic data is essential.

Scabies and associated impetigo are under-recognized causes of morbidity in many developing countries. To strengthen the evidence base for scabies control we undertook a trial of mass treatment for scabies. We report on the occurrence and predictors of scabies and impetigo in participants at baseline. Participants were recruited in six island communities and were examined for the presence of scabies and impetigo. In addition to descriptive analyses, logistic regression models were fit to assess the association between demographic variables and outcome of interest. The study enrolled 2051 participants. Scabies prevalence was 36.4% (95% confidence interval [CI] 34.3–38.5), highest in children 5–9 years (55.7%). Impetigo prevalence was 23.4% (95% CI 21.5–25.2) highest in children aged 10–14 (39.0%). People with scabies were 2.8× more likely to have impetigo. The population attributable risk of scabies as a cause of impetigo was 36.3% and 71.0% in children aged less than five years. Households with four or more people sharing the same room were more likely to have scabies and impetigo (odds ratios [OR] 1.6, 95% CI 1.2–2.2 and OR 2.3, 95% CI 1.6–3.2 respectively) compared to households with rooms occupied by a single individual. This study confirms the high burden of scabies and impetigo in Fiji and the association between these two conditions, particularly in young children. Overcrowding, young age, and clinical distribution of lesion are important risk factors for scabies and impetigo. Further studies are needed to investigate whether the decline of endemic scabies would translate into a definite reduction of the burden of associated complications.

BACKGROUND: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. METHODS: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3μg/ml but 4.0μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose. RESULTS: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of serotypes with a positive response. CONCLUSION: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.

Background: The burden of acute lower respiratory infection (ALRI) in Indigenous children of Australia's Northern Territory is among the highest globally. No published data exists on the effect of pneumococcal conjugate vaccine (PCV) introduction on ALRIs in this population beyond 2005. The aim of this study was to describe the rates of ALRI admissions to hospital in Indigenous infants in the Northern Territory from 2006 to 2015, across three periods of different PCV use. We hypothesised that broader valency PCVs would be more effective against hospitalisations for pneumonia. Methods: We did a retrospective population-based cohort study of Indigenous infants born in the Northern Territory followed up until age 12 months. Data were from administrative hospital and perinatal datasets. International classification of diseases codes (tenth revision, Australian modification; ICD-10AM) were used to identify respiratory hospitalisations of interest: all-cause ALRI, all-cause pneumonia, bacterial pneumonia, viral pneumonia, influenza-like illness (ILI), respiratory syncytial virus ALRI (RSV-ALRI), and pneumococcal ALRI. Incidence rates were compared between PCV eras (7-valent PCV [PCV7], 2006–09; 10-valent PCV [PCV10], 2009–11; and 13-valent PCV [PCV13], 2011–15) using interrupted time trend analysis and negative binomial regression. Findings: For children born between Jan 1, 2006, and Dec 31, 2015, 4138 ALRI episodes (31% of all hospitalisations) occurred among 2888 (20%) of the 14 594 infants. The overall ALRI hospitalisation rate was 29·7 episodes per 100 child-years. Prominent risk factors associated with ALRI hospitalisation were living in a remote community or the Central desert region, being born preterm or with low birthweight. ALRI rates were lowest in the PCV13 era, in association with a significant reduction in bacterial pneumonia hospitalisations in the PCV13 era compared with the PCV10 (incidence rate ratio 0·68, 95% CI 0·57–0·81) and PCV7 (0·70, 0·60–0·81) eras. In contrast, RSV-ALRI rates were 4·9 episodes per 100 child-years in each era. Interpretation: A 30% reduction in bacterial-coded pneumonia hospitalisations in the Northern Territory during the era of PCV13 immunisation supports its ongoing use in the region. Despite the reduction, one in five Indigenous infants born in the region continue to be hospitalised with an ALRI in their first year of life. Future gains require multifaceted environmental and biomedical approaches. Funding: National Health and Medical Research Council of Australia.

Remote-living Aboriginal and Torres Strait Islander women experience a higher burden of influenza infection during pregnancy than any other Australian women. Despite recommendations of inactivated influenza vaccination (IIV) in pregnancy, uptake and safety data are scarce for this population. We examined uptake of IIV in pregnancy and report adverse birth outcomes amongst a predominantly unvaccinated group of remote-living Aboriginal and Torres Strait Islander women from the Northern Territory (NT), using data from the 1+1 Healthy Start to Life study. Data were deterministically linked with the NT Immunisation Register to ascertain IIV exposure in pregnant women during 2003–2006 and 2009–2011 inclusive. Overall, IIV uptake in pregnancy was 3% (n=20/697 pregnancies); 0% (0/414) pre-influenza A(H1N1)pdm09 and 7% (20/293) post-influenza A(H1N1)pdm09 (2009–2011). Vaccine uptake was poor in this cohort and it is unclear at what stage this policy failure occurred. Women with known comorbidities and/or high risk factors were not targeted for vaccination. Much larger study participant numbers are required to validate between group comparisons but there was no clinically nor statistically significant difference in median gestational ages (38 weeks for both groups), mean infant birthweights (3,001 g unvaccinated vs 3,175 g IIV vaccinated), nor birth outcomes between the few women who received IIV in pregnancy and those who did not. There were no stillbirths in women who received an IIV in pregnancy.

Receiving vaccines at or close to their due date (vaccination timeliness) is a now key measure of program performance. However, studies comprehensively examining predictors of delayed infant vaccination are lacking. We aimed to identify predictors of short and longer-term delays in diphtheria-tetanus-pertussis (DTP) vaccination by dose number and ethnicity.Perinatal, notification, death and immunisation databases were linked for 1.3 million births in 2000-11 from two Australian states (Western Australia and New South Wales), with follow-up data until 2013. Ordinal logistic regression was used to estimate adjusted relative risks (RR) by degree of delay. Separate models were constructed for each vaccine dose and for Aboriginal and non-Aboriginal children.Each dose-specific cohort included at least 49,000 Aboriginal and 1.1 million non-Aboriginal children. Delayed receipt was more common among Aboriginal than non-Aboriginal children (eg for the first dose of DTP [DTP1] 19.4 v 8.1%). Risk factors for delayed vaccination were strongest for DTP1, and delayed receipt of DTP1 was a key driver of subsequent delays; every week DTP1 was delayed was associated with a 1.6 to 2-fold increased risk of delayed DTP2 receipt. For DTP1, ≥3 previous pregnancies (the only factor more strongly associated with longer than shorter delays; RR ≥5 compared to no previous pregnancies), and children born to mothers20 years of age (RR ≥2 compared to ≥35 years) were at highest risk of delay. Other independent predictors were prematurity, maternal smoking during pregnancy, and being born in Western Australia (if Aboriginal) or another country in the Oceania region.The sub-populations at risk for delayed vaccination we have identified are likely generalisable to other high-income settings. Measures to improve their dose 1 timeliness, particularly for children with older siblings, are likely to have significant flow-on benefits for timeliness of later doses.

Ivermectin for Scabies In this 2-year follow-up report in Fiji, the single mass administration of oral ivermectin was more effective in reducing the prevalence of both scabies and impetigo than eit...

IntroductionPregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes.Methods and analysis‘Links2HealthierBubs’ is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (~607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers.Ethics and disseminationEthical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women’s Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public.

Increasing numbers of cases of invasive pneumococcal disease in fully vaccinated children have occurred in Australia since 2013. A review of cases informed a change from a “3 + 0” infant schedule (13-valent pneumococcal conjugate vaccine at 2, 4, and 6 months) to a “2 + 1” schedule (2, 4, and 12 months).

Background:­­­­ For Indigenous infants living in Australia’s Northern Territory (NT) acute lower respiratory infections (ALRIs) are a leading cause of hospitalisation and preventable mortality. The study describes the burden of ALRI hospitalisation in this population from 2006 to 2015 with contrast between three periods of different pneumococcal conjugate vaccine (PCV) use. Methods: We conducted a historical cohort study of NT Indigenous infants born between 1st January 2006 and 31st December 2015 and followed until age 12 months. Data were from administrative hospital and perinatal datasets. International classification of diseases codes were used to identify respiratory hospitalisations of interest: all cause ALRI, all cause pneumonia, bacterial pneumonia, viral pneumonia, influenza-like illness (ILI), respiratory syncytial virus ALRI (RSV-ALRI) and pneumococcal ALRI. Incidence rates were compared between PCV eras (7-valent PCV-PCV7, 2006-2009; PCV10, 2009-2011; PCV13, 2011-2015) using interrupted time trend analysis and negative binomial regression. Findings: Over the study period 4138 ALRI episodes (31% of all hospitalisations) occurred among 2888 of the 14594 infants (20% of the cohort). The overall ALRI hospitalisation rate was 29.7 episodes per 100 child-years. Prominent risk factors associated with ALRI hospitalisation were living in a remote community or the Central desert region, being born preterm or with low birth weight. ALRI rates were lowest in the PCV13 era in association with a significant reduction in bacterial pneumonia hospitalisations in the PCV13 relative to the PCV10 (IRR 0∙68, 95% CI 0∙57-0∙81) and PCV7 (IRR 0∙70, 95% CI 0∙60-0∙81) eras. In contrast, RSV-ALRI rates were 4∙9 episodes per 100 child-years in each era. Interpretation: We found a 30% reduction in bacterial-coded pneumonia hospitalisation episodes during the era of PCV13 use. Despite this, one in five NT Indigenous infants continue to be hospitalised with an ALRI in their first year of life. RSV associated ALRI rates were high and remained unchanged over a decade. Funding Statement: This work was supported by the National Health and Medical Research Council (NHMRC) of Australia. MJB was funded by an NHMRC Early Career Fellowship (1088733) and NHMRC-funded `Hot North - Improving Health Outcomes in the Tropical North’ Fellowship (1131932). JB is supported by a NHMRC scholarship (1150901) and a NHMRC-funded Centre of Research Excellence in Ear and Hearing Health of Aboriginal and Torres Strait Islander children scholarship (1078557). VMO none. SJP was supported by a NHMRC Peter Doherty Early Career Fellowship (1113302). AJL was supported by NHMRC Fellowship (1020561), the NHMRC-funded Centre of Research Excellence in Ear and Hearing Health of Aboriginal and Torres Strait Islander Children (1078557), The Balnaves Foundation, the Northern Territory Government and the Australian Government. PSM none. RMA none. LM was supported by an Australian Postgraduate Award through Charles Darwin University and an Enhanced Living scholarship through Menzies School of Health Research towards a Doctor of Philosophy degree. RW none. ABC is supported by Australia’s NHMRC Practitioner Fellowship (1058213) and a Children’s Hospital Foundation Fellowship, Queensland (50286). Declaration of Interests: The authors stated: "None exist." Ethics Approval Statement: This project was approved by the Human Research Ethics Committee of the NT Department of Health and Menzies School of Health Research (HREC 2015-2406).

Background Indigenous children in Australia’s Northern Territory are densely colonised with the pneumococcus within weeks of birth antecedent to a high prevalence of acute lower respiratory infection (ALRI). We assessed the impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPV) in pregnancy against infant ALRI in this setting. Methods In an open label, allocation concealed, outcome-assessor blinded, randomised controlled trial conducted in the Northern Territory of Australia, healthy Indigenous women aged 17–39 years were randomised to receive the 23vPPV during pregnancy (n = 75; 30–36 weeks gestation), at birth (n = 75), or at 7 months post-partum (n = 77). Randomisation was stratified by community of residence. In a secondary analysis, we compared the incidence of ALRI hospitalisations and ALRI clinic presentations (ascertained from electronic medical records) among infants of pregnancy vaccinees versus infants of mothers not vaccinated in pregnancy (controls) in the first year of life. Results ALRI hospitalisation incidence was 12.3 per 100 child-years among infants of pregnancy vaccinees compared with 15.8 per 100 child-years among controls (hazard ratio (HR) 0.77, 95%CI 0.29–2.03). ALRI hospitalisations were more common among remote compared to urban infants (27.7 versus 8.6 per 100 child-years). Stratification by dwelling highlighted a differential antenatal vaccine effect against ALRI hospitalisations (urban HR 2.45, 95%CI 0.60–9.99; remote HR 0.21, 95%CI 0.04–1.08). ALRI clinic presentation incidence was similar among infants of pregnancy vaccinees and controls. Conclusions In this small study, antenatal 23vPPV vaccination was not associated with a reduced incidence of infant ALRI hospitalisations or ALRI clinic presentations during the first year of life. A potential differential effect between urban and remote settings warrants further investigation. Trial registration PneuMum; ClinicalTrials.gov NCT00714064. Electronic supplementary material The online version of this article (10.1186/s41479-018-0057-2) contains supplementary material, which is available to authorized users.

Background Soil-transmitted helminths (STHs) including Ascaris lumbricoides, Necator americanus, Ancylostoma spp. and Trichuris trichiura are cause of significant global morbidity. To mitigate their disease burden, at-risk groups in endemic regions receive periodic mass drug administration using anthelmintics, most commonly albendazole and mebendazole. Assessing the efficacy of anthelmintic drugs is important for confirming that these regimens are working effectively and that drug resistance has not emerged. In this study we aimed to characterise the therapeutic efficacy of albendazole against Ascaris spp. and N. americanus in Timor-Leste, using a quantitative polymerase chain reaction (qPCR) method for parasite detection and quantification. Results A total of 314 participants from 8 communities in Timor-Leste provided stool samples before and 10–14 days after the administration of a single 400 mg dose of albendazole. Helminth infection status and infection intensity (measured in Ct-values and relative fluorescence units) were determined using qPCR. Efficacy was determined by examining the cure rates and infection intensity reduction rates. Albendazole was found to be highly efficacious against Ascaris spp., with a cure rate of 91.4% (95% CI: 85.9–95.2%) and infection intensity reduction rate of 95.6% (95% CI: 88.3–100%). The drug was less efficacious against N. americanus with a cure rate of 58.3% (95% CI: 51.4–64.9%) and infection intensity reduction rate of 88.9% (95% CI: 84.0–97.0%). Conclusions The observed cure rates and infection intensity reduction rates obtained for Ascaris spp. and to a lower extent N. americanus, demonstrate the continued efficacy of albendazole against these species and its utility as a mass chemotherapy agent in Timor-Leste. Furthermore, this study demonstrates the usefulness of qPCR as a method to measure the efficacy of anthelminthic drugs. Additional research is necessary to translate Ct-values into eggs per gram in a systematic way. Trial registration Australian and New Zealand Clinical Trials Registry 12614000680662 (registered 27 June 2014).

Objective To quantify the childhood infectious disease burden and antibiotic use in the Northern Territory's East Arnhem region through synthesis and analysis of historical data resources. Methods We combined primary health clinic data originally reported in three separate publications stemming from the East Arnhem Healthy Skin Project (Jan-01 to Sep-07). Common statistical techniques were used to explore the prevalence of infectious conditions and the seasonality of infections, and to measure rates of antibiotic use. Results There was a high monthly prevalence of respiratory (mean: 32% [95% confidence interval (CI): 20%, 34%]) and skin (mean: 20% [95%CI: 19%, 22%]) infectious syndromes, with upper respiratory tract infections (mean: 29% [95%CI: 27%, 31%]) and skin sores (mean: 15% [95%CI: 14%, 17%]) the most common conditions. Antibiotics were frequently prescribed with 95% (95%CI: 91%, 97%) of children having received at least one antibiotic prescription by their first birthday, and 47% having received six antibiotic prescriptions; skin sores being a key driver. Conclusions Early life infections drive high antibiotic prescribing rates in remote Aboriginal communities. Implications for public health: Eliminating skin disease could reduce antibiotic use by almost 20% in children under five years of age in this population.

The burden of skin infections across all age groups in remote Australian Indigenous communities is currently unknown. In a retrospective audit of 439 residents from two remote communities presenting to health clinics, skin conditions were the most common reason for presentation (1603/7392, 22%) and 330/439 (75%) residents presented at least once with a skin infection. Skin infections are an under-appreciated and dominant reason for presentation to primary healthcare centres in these indigenous communities and public health campaigns to address this should incorporate all age groups.

Background: Inactivated influenza vaccine (IIV) and pertussis vaccination are recommended in pregnancy. Limited safety data exist for women who received IIV vaccine during the first trimester of pregnancy or received both vaccines in pregnancy. We assessed adverse birth outcomes between vaccinated and unvaccinated pregnancies. Methods: Among prospectively enrolled Australian "FluMum" participants (2012-2015), primary exposure was receipt and timing of IIV during pregnancy. Primary outcomes included preterm birth, low birthweight at term (LBWT), and small for gestational age (SGA). We compared birth outcomes for IIV in pregnancy with women unvaccinated in pregnancy using Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). Adjusted HRs (aHRs) controlled for potential confounding variables. Sensitivity analyses were conducted in a subgroup of women who received pertussis vaccination during pregnancy to assess whether associations between IIV and adverse outcomes were maintained after adjusting for pertussis vaccination. Results: Among 8827 participants in our study, women who received IIV in pregnancy did not have an elevated risk of an adverse birth outcome compared with unvaccinated pregnant women: preterm births (HR, 1.10 [95% CI, .92-1.31]; P = .28); LBWT (HR, 1.05 [95% CI, .76-1.44]; P = .77); or SGA (HR, 0.99 [95% CI, .86-1.15]; P = .94). Adjustment for pertussis vaccination during pregnancy yielded similar results: preterm births (aHR, 1.05 [95% CI, .82-1.34]; P = .69); LBWT (aHR, 0.81 [95% CI, .50-1.29]; P = .37); SGA (aHR, 0.92 [95% CI, .74-1.14]; P = .43). There was no evidence of elevated risk by trimester of IIV. Conclusions: No significant associations were found between maternal IIV or pertussis vaccination in pregnancy and adverse birth outcomes, regardless of the trimester of pregnancy a vaccination was given compared to unvaccinated pregnancies.

Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia's national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births.Births records for 2001-2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 - adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children.Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9-98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5-94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4-90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children.Our population-based cohort study demonstrates that90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.

SUMMARYPertussis morbidity is highest in infants too young to be fully protected by routine vaccination schedules. Alternate vaccine strategies are required to maximise protection in this age-group. To understand baseline pertussis epidemiology prior to the introduction of the maternal pertussis vaccination program in 2014, we conducted a retrospective case series analyses of 53 901 notifications and temporal trends from 1997 to 2014. Notifications were highest in infants younger than 4 months of age and highest annual notification rates in infants younger than 1 month of age (308/100 000 per year). Amongst Aboriginal and Torres Strait Islander infants aged younger than 1 month, this rate was 576/100 000 per year. Notification rates were 40% higher amongst women 15–44 years, 62·4/100 000 population compared with men (44·5/100 000) and 90% higher in Aboriginal and Torres Strait Islander women of the same age (38·2/100 000) compared with men (19·7/100 000). Six infant deaths were identified, all younger than 2 months of age. Monitoring epidemiology in at-risk groups – infants too young to be vaccinated, women of childbearing age and Aboriginal and Torres Strait Islander peoples – following implementation of the maternal pertussis vaccination program will be important to assess its impact and safety.

Background Timor-Leste has a high prevalence of soil-transmitted helminth (STH) infections. High proportions of the population have been reported as being anaemic, and extremely high proportions of children as stunted or wasted. There have been no published analyses of the contributions of STH to these morbidity outcomes in Timor-Leste. Methods Using baseline cross-sectional data from 24 communities (18 communities enrolled in a cluster randomised controlled trial, and identically-collected data from six additional communities), analyses of the association between STH infections and community haemoglobin and child development indices were undertaken. Stool samples were assessed for STH using qPCR and participant haemoglobin, heights and weights were measured. Questionnaires were administered to collect demographic and socioeconomic data. Intensity of infection was categorised using correlational analysis between qPCR quantification cycle values and eggs per gram of faeces equivalents, with algorithms generated from seeding experiments. Mixed-effects logistic and multinomial regression were used to assess the association between STH infection intensity classes and anaemia, and child stunting, wasting and underweight. Results Very high stunting (60%), underweight (60%), and wasting (20%) in children, but low anaemia prevalence (15%), were found in the study communities. STH were not significantly associated with morbidity outcomes. Male children and those in the poorest socioeconomic quintile were significantly more likely to be moderately and severely stunted. Male children were significantly more likely than female children to be severely underweight. Increasing age was also a risk factor for being underweight. Few risk factors emerged for wasting in these analyses. Conclusions According to World Health Organization international reference standards, levels of child morbidity in this population constitute a public health emergency, although the international reference standards need to be critically evaluated for their applicability in Timor-Leste. Strategies to improve child development and morbidity outcomes, for example via nutrition and iron supplementation programmes, are recommended for these communities. Despite the apparent lack of an association from STH in driving anaemia, stunting, wasting and underweight, high endemicity suggests a need for STH control strategies. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12614000680662; retrospectively registered. Electronic supplementary material The online version of this article (doi:10.1186/s13071-017-2084-x) contains supplementary material, which is available to authorized users.

Pregnant Aboriginal and Torres Strait Islander women are at particular risk of severe illness and high attack rates of influenza infection. In Australia, routine seasonal influenza vaccination is currently strongly recommended for all pregnant women and women planning pregnancy, and is provided free of charge for all pregnant women. We sought to determine vaccination coverage, describe the trends and characteristics associated with influenza vaccine uptake and determine the validity of self-reported influenza vaccination in a population of Indigenous pregnant women who were participants of a vaccine trial, prior to and during the 2009 H1N1 influenza pandemic. Vaccine coverage over the study period was 16% (35/214), increasing from 2.2% (3/136) in the period preceding the pandemic (2006-2009) to 41% (32/78) in the intra-pandemic period (2009-2010). Self-report was not a reliable estimate of verified vaccination status in the pre-pandemic period (κ=0.38) but was reliable in the intra-pandemic period (κ=0.91). None of the socio-demographic characteristics that we examined were associated with vaccine uptake. Whilst the increase in maternal influenza coverage rates are encouraging and indicate a willingness of pregnant Indigenous women to be vaccinated, the majority of women remained unvaccinated. Activities to improve influenza vaccination coverage for Indigenous pregnant women and monitor vaccine uptake remain a priority. Commun Dis Intell 2016;40(3):E340-E346.

An approach to improve the diagnosis of Strongyloides stercoralis infection is the use of serologic assays utilising the NIE antigen from S. stercoralis, with good diagnostic sensitivity and excellent specificity reported. Detection of antibody eluted from dried blood spots (DBS) has shown utility in large-scale seroepidemiological studies for a range of conditions and is appealing for use with children where sample collection is difficult. We adapted an existing NIE-enzyme linked immunosorbent assay (ELISA) for the testing of strongyloides antibody response on DBS, and evaluated it in a population screening and mass drug administration programme (MDA) for strongyloidiasis conducted in an Australian indigenous community. Study participants were treated with 200 μg/kg ivermectin (>15 kg) or 3× 400 mg albendazole (

Aim Acute lower respiratory infections (ALRIs) are the most common reason for hospitalisation of young children in the Northern Territory of Australia. International studies have linked vitamin D deficiency with increased risk of ALRI in paediatric populations, but this has not been explored in tropical regions such as the Top End of the Northern Territory. The aim of this study is to determine the prevalence of vitamin D insufficiency among children hospitalised with ALRI in the Northern Territory. Methods Vitamin D serum metabolite (25OHD3) levels were retrospectively measured using liquid chromatography-mass spectrometry in 74 children (64% male; 57% Indigenous) aged less than 3 years admitted to Royal Darwin Hospital in the Northern Territory of Australia between May 2008 and May 2010. Results There were 44 (59%) ALRI-classified hospitalisations and 30 (41%) non-ALRI-classified hospitalisations. The most common ALRI diagnoses were bronchiolitis (n = 22, 30%) and pneumonia (n = 21, 28%), whereas the most common non-ALRI diagnosis was gastroenteritis (n = 20, 27%). Overall, 24/74 (32%) children had 25OHD3 levels

Infections with Sarcoptes scabiei, or scabies, remain common in many disadvantaged populations. Mass drug administration (MDA) has been used in such settings to achieve a rapid reduction in infection and transmission, with the goal of eliminating the public health burden of scabies. While prevalence has been observed to fall substantially following such an intervention, in some instances resurgence of infection to baseline levels has occurred over several years. To explore the biology underpinning this phenomenon, we have developed a theoretical model of scabies life-cycle and transmission dynamics in a homogeneously mixing population, and simulate the impact of mass drug treatment strategies acting on egg and mite life cycle stages (ovicidal) or mites alone (non-ovicidal). In order to investigate the dynamics of the system, we first define and calculate the optimal interval between treatment doses. We calculate the probability of eradication as a function of the number of optimally-timed successive treatment doses and the number of years over which a program is run. For the non-ovicidal intervention, we first show that at least two optimally-timed doses are required to achieve eradication. We then demonstrate that while more doses over a small number of years provides the highest chance of eradication, a similar outcome can be achieved with fewer doses delivered annually over a longer period of time. For the ovicidal intervention, we find that doses should be delivered as close together as possible. This work provides a platform for further research into optimal treatment strategies which may incorporate heterogeneity of transmission, and the interplay between MDA and enhancement of continuing scabies surveillance and treatment strategies.

Introduction In Australia, influenza vaccination is recommended for all women who will be pregnant during the influenza season. Vaccine safety and effectiveness are key concerns and influencers of uptake for both vaccine providers and families. We assessed the safety of receiving an influenza vaccination during any trimester of pregnancy with respect to preterm births and infant birthweight. Methods We conducted a nested retrospective cohort study of ‘FluMum’ participants (2012–2014). Our primary exposure of interest was influenza vaccination during pregnancy. The primary outcomes of interest were infant birthweight and weeks’ gestation at birth for live singleton infants. Analyses included comparisons of these birth outcomes by vaccination status and trimester of pregnancy an influenza vaccine was given. We calculated means, proportions, and relative risks and performed multivariable logistic regression for potential confounding factors. Results In the 7126 mother-infant pairs enrolled in this study, mean maternal age at infant birth was 31.7 years. Influenza vaccine uptake in pregnancy was 34%. Most mothers with a known date of vaccination received a vaccine in the second trimester (51%). Those mothers with a co-morbidity or risk factor were 13% more likely to have influenza vaccine during pregnancy compared to other mothers (RR 1.13, 95% CI 1.04–1.24, p = 0.007). Mean weeks’ gestation at birth was 38.7 for the vaccinated and 38.8 for the unvaccinated group (p = 0.051). Infants in the vaccinated group weighed 15 g less in birthweight compared to the unvaccinated infants (95% CI −12.8 to 42.2, p = 0.29). Conclusion Results arising from this large Australian cohort study are reassuring with respect to two critical safety outcomes; preterm births and low infant birthweights. Studies examining a broader range of birth outcomes following influenza vaccination during pregnancy are required, particularly now that maternal vaccination in pregnancy has expanded to include pertussis as well as influenza.

In the past 200 years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. Highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. We examine immunization vaccine policy as a driver of vaccine innovation and development. The pathways to recommendation for use of licensed vaccines in the US, UK, Canada and Australia have been similar, including: expert review of disease epidemiology, disease burden and severity; vaccine immunogenicity, efficacy and safety; programmatic feasibility; public demand; and increasingly cost-effectiveness. Other attributes particularly important in development of future vaccines are likely to include: duration of immunity for improved vaccines such as pertussis; a greater emphasis on optimizing community protection rather than direct protection only; programmatic implementation, feasibility, improvements (as in the case of development of a universal influenza vaccine); public concerns/confidence/fears related to outbreak pathogens like Ebola and Zika virus; and major societal burden for combating hard to treat diseases like HIV and antimicrobial resistant pathogens. Driving innovation and production of future vaccines faces enormous economic hurdles as available approaches, technologies and regulatory pathways become more complex. As such, cost-mitigating strategies and focused, aligned efforts (by governments, private organizations, and private-public partnerships) will likely be needed to continue to spur major advances in vaccine technologies and development.

There is little evidence on prevalence or risk factors for soil transmitted helminth infections in Timor-Leste. This study describes the epidemiology, water, sanitation and hygiene, and socioeconomic risk factors of STH and intestinal protozoa amongst communities in Manufahi District, Timor-Leste. As part of a cluster randomised controlled trial, a baseline cross-sectional survey was conducted across 18 villages, with data from six additional villages. Stool samples were assessed for soil transmitted helminth and protozoal infections using quantitative PCR (qPCR) and questionnaires administered to collect water, sanitation and hygiene and socioeconomic data. Risk factors for infection were assessed using multivariable mixed-effects logistic regression, stratified by age group (preschool, school-aged and adult). Overall, soil transmitted helminth prevalence was 69% (95% Confidence Interval 67-71%), with Necator americanus being most common (60%; 95% Confidence Interval 58-62%) followed by Ascaris spp. (24%; 95% Confidence Interval 23-26%). Ascaris-N. americanus co-infection was common (17%; 95% Confidence Interval 15%-18%). Giardia duodenalis was the main protozoan identified (13%; 95% Confidence Interval 11-14%). Baseline water, sanitation and hygiene infrastructure and behaviours were poor. Although risk factors varied by age of participants and parasite species, risk factors for N. americanus infection included, generally, age in years, male sex, and socioeconomic quintile. Risk factors for Ascaris included age in years for children, and piped water to the yard for adults. In this first known assessment of community-based prevalence and associated risk factors in Timor-Leste, soil transmitted helminth infections were highly prevalent, indicating a need for soil transmitted helminth control. Few associations with water, sanitation and hygiene were evident, despite water, sanitation and hygiene being generally poor. In our water, sanitation and hygiene we will investigate implications of improving WASH on soil transmitted helminth infection in impoverished communities.