Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool

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The p60 and NamA autolysins from Listeria monocytogenes contribute to host colonization and induction of protective memory

Inducing long‐term protective memory CD8⁺ T‐cells is a desirable goal for vaccines against intracellular pathogens. However, the mechanisms of differentiation of CD8⁺ T‐cells into long‐lived memory cells capable of mediating protection of immunized hosts remain incompletely understood. We have developed an experimental system using mice immunized with wild type (WT) or mutants of the intracellular bacterium Listeria monocytogenes (Lm) that either do or do not develop protective memory CD8⁺ T‐cells. We previously reported that mice immunized with Lm lacking functional SecA2, an auxiliary secretion system of gram‐positive bacteria, did not differentiate functional memory CD8⁺ T‐cells that protected against a challenge infection with WT Lm. Herein we hypothesized that the p60 and NamA autolysins of Lm, which are major substrates of the SecA2 pathway, account for this phenotype. We generated Lm genetically deficient for genes encoding for the p60 and NamA proteins, ΔiapΔmurA Lm, and further characterized this mutant. Δp60ΔNamA Lm exhibited a strong filamentous phenotype, inefficiently colonized host tissues, and grew mostly outside cells. When Δp60ΔNamA Lm was made single unit, cell invasion was restored to WT levels during vaccination, yet induced memory T‐cells still did not protect immunized hosts against recall infection. Recruitment of blood phagocytes and antigen‐presenting cell activation was close to that of mice immunized with ΔActA Lm, which develop protective memory. However, key inflammatory factors involved in optimal T‐cell programming such as IL‐12 and type I IFN (IFN‐I) were lacking, suggesting that cytokine signals may largely account for the observed phenotype. Thus, altogether, these results establish that p60 and NamA secreted by Lm promote primary host cell invasion, the inflammatory response and the differentiation of functional memory CD8⁺ T‐cells, by preventing Lm filamentation during growth and subsequent triggering of innate sensing mechanisms.     

Adverse Obstetric and Perinatal Outcomes following Treatment of Adolescent and Young Adult Cancer: A Population-Based Cohort Study

Objective

To investigate obstetric and perinatal outcomes among female survivors of adolescent and young adult (AYA) cancers and their offspring.

Methods

Using multivariate analysis of statewide linked data, outcomes of all first completed pregnancies (n = 1894) in female survivors of AYA cancer diagnosed in Western Australia during the period 1982–2007 were compared with those among females with no cancer history. Comparison pregnancies were matched by maternal age-group, parity and year of delivery.

Results

Compared with the non-cancer group, female survivors of AYA cancer had an increased risk of threatened abortion (adjusted relative risk 2.09, 95% confidence interval 1.51–2.74), gestational diabetes (2.65, 2.08–3.57), pre-eclampsia (1.32, 1.04–1.87), post-partum hemorrhage (2.83, 1.92–4.67), cesarean delivery (2.62, 2.22–3.04), and maternal postpartum hospitalization>5 days (3.01, 1.72–5.58), but no excess risk of threatened preterm delivery, antepartum hemorrhage, premature rupture of membranes, failure of labor to progress or retained placenta. Their offspring had an increased risk of premature birth (<37 weeks: 1.68, 1.21–2.08), low birth weight (<2500 g: 1.51, 1.23–2.12), fetal growth restriction (3.27, 2.45–4.56), and neonatal distress indicated by low Apgar score (<7) at 1 minute (2.83, 2.28–3.56), need for resuscitation (1.66, 1.27–2.19) or special care nursery admission (1.44, 1.13–1.78). Congenital abnormalities and perinatal deaths (intrauterine or ≤7 days of birth) were not increased among offspring of survivors.

Conclusion

Female survivors of AYA cancer have moderate excess risks of adverse obstetric and perinatal outcomes arising from subsequent pregnancies that may require additional surveillance or intervention.     

Assisted Vaginal Deliveries in Mothers Admitted as Public or Private Patients in Western Australia

Background

Mothers delivering as private patients in Australia have a high rate of assisted deliveries, which could lead to adverse infant outcomes in this group of patients. We investigated whether the risk of adverse infant outcomes after assisted deliveries was different for mothers admitted as public or private patients for delivery, when compared with unassisted deliveries.

Methods and findings

We included 158,241 vaginal, singleton, term birth admissions in our study where the infant was live born and without birth defects. The study population was identified from statutory birth and hospital data collections held by the Western Australian (WA) Department of Health. We estimated odds ratios and confidence intervals using logistic regression models adjusted for a range of maternal demographic, pregnancy and birth characteristics. Interaction was assessed by including interaction terms in the models. Outcomes included low Apgar scores at five minutes (<7), neonatal resuscitation and special care admission. Mothers delivering as private patients had an increased risk of assisted vaginal delivery compared with public patients (adjusted OR 1.74, 95% CI = 1.68–1.80). Compared with unassisted vaginal deliveries, assisted deliveries were associated with increased risk of Apgar scores at five minutes below 7 (OR 1.25, 1.08–1.45), neonatal resuscitation (OR = 1.69, 1.42–2.00) and admission to special care nursery (OR = 1.64, 1.53–1.76). The increased risk of neonatal resuscitation was higher for mothers admitted as private patients for delivery (OR = 2.13) than public patients (OR = 1.55, p^interaction = 0.03).

Conclusions

Our results suggested that the high risk of neonatal resuscitation following assisted vaginal deliveries compared to unassisted is higher in private patients than public patients. Whether this phenomenon is due to the twofold higher rate of assisted vaginal deliveries in this group of patients or a higher rate of fetal indications for assisted vaginal delivery remains to be answered.     

Increase in caesarean deliveries after the Australian private health insurance incentive policy reforms

Background

The Australian Private Health Insurance Incentive (PHII) policy reforms implemented in 1997–2000 increased PHI membership in Australia by 50%. Given the higher rate of obstetric interventions in privately insured patients, the reforms may have led to an increase in surgical deliveries and deliveries with longer hospital stays. We aimed to investigate the effect of the PHII policy introduction on birth characteristics in Western Australia (WA).

Methods and Findings

All 230,276 birth admissions from January 1995 to March 2004 were identified from administrative birth and hospital data-systems held by the WA Department of Health. Average quarterly birth rates after the PHII introduction were estimated and compared with expected rates had the reforms not occurred. Rate and percentage differences (including 95% confidence intervals) were estimated separately for public and private patients, by mode of delivery, and by length of stay in hospital following birth. The PHII policy introduction was associated with a 20% (−21.4 to −19.3) decrease in public birth rates, a 51% (45.1 to 56.4) increase in private birth rates, a 5% (−5.3 to −5.1) and 8% (−8.9 to −7.9) decrease in unassisted and assisted vaginal deliveries respectively, a 5% (−5.3 to −5.1) increase in caesarean sections with labour and 10% (8.0 to 11.7) increase in caesarean sections without labour. Similarly, birth rates where the infant stayed 0–3 days in hospital following birth decreased by 20% (−21.5 to −18.5), but rates of births with >3 days in hospital increased by 15% (12.2 to 17.1).

Conclusions

Following the PHII policy implementation in Australia, births in privately insured patients, caesarean deliveries and births with longer infant hospital stays increased. The reforms may not have been beneficial for quality obstetric care in Australia or the burden of Australian hospitals.     

The Australian Baby Bonus Maternity Payment and Birth Characteristics in Western Australia

Background

The Australian baby bonus maternity payment introduced in 2004 has been reported to have successfully increased fertility rates in Australia. We aimed to investigate the influence of the baby bonus on maternal demographics and birth characteristics in Western Australia (WA).

Methods and Findings

This study included 200,659 birth admissions from WA during 2001–2008, identified from administrative birth and hospital data-systems held by the WA Department of Health. We estimated average quarterly birth rates after the baby bonus introduction and compared them with expected rates had the policy not occurred. Rate and percentage differences (including 95% confidence intervals) were estimated separately by maternal demographics and birth characteristics. WA birth rates increased by 12.8% following the baby bonus implementation with the greatest increase being in mothers aged 20–24 years (26.3%, 95%CI = 22.0,30.6), mothers having their third (1.6%, 95%CI = 0.9,2.4) or fourth child (2.2%, 95%CI = 2.1,2.4), mothers living in outer regional and remote areas (32.4%, 95%CI = 30.2,34.6), mothers giving birth as public patients (1.5%, 95%CI = 1.3,1.8), and mothers giving birth in public hospitals (3.5%, 95%CI = 2.6,4.5). Interestingly, births to private patients (−4.3%, 95%CI = −4.8,−3.7) and births in private hospitals (−6.3%, 95%CI = −6.8,−5.8) decreased following the policy implementation.

Conclusions

The introduction of the baby bonus maternity payment may have served as an incentive for women in their early twenties and mothers having their third or fourth child and may have contributed to the ongoing pressure and staff shortages in Australian public hospitals, particularly those in outer regional and remote areas.     

Factors associated with soil-transmitted helminths infection in Benin: Findings from the DeWorm3 study

BackgroundDespite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster-randomized trials in Benin, India and Malawi. We used the pre-treatment baseline survey data to describe and analyze the factors associated with STH infection in Comé, the study site of the DeWorm3 project in Benin. These data will improve understanding of the challenges that need to be addressed in order to eliminate STH as a public health problem in Benin.MethodsBetween March and April 2018, the prevalence of STH (hookworm spp., Ascaris and Trichuris trichiura) was assessed by Kato-Katz in stool samples collected from 6,153 residents in the community of Comé, Benin using a stratified random sampling procedure. A standardized survey questionnaire was used to collect information from individual households concerning factors potentially associated with the presence and intensity of STH infections in pre-school (PSAC, aged 1–4), school-aged children (SAC, aged 5–14) and adults (aged 15 and above). Multilevel mixed-effects models were used to assess associations between these factors and STH infection.ResultsThe overall prevalence of STH infection was 5.3%; 3.2% hookworm spp., 2.1% Ascaris lumbricoides and 0.1% Trichuris. Hookworm spp. were more prevalent in adults than in SAC (4.4% versus 2.0%, respectively; p = 0.0001) and PSAC (4.4% versus 1.0%, respectively; p<0.0001), whilst Ascaris lumbricoides was more prevalent in SAC than in adults (3.0% versus 1.7%, respectively; p = 0.004). Being PSAC (adjusted Odds Ratio (aOR) = 0.2, p< 0.001; adjusted Infection Intensity Ratio (aIIR) = 0.1, p<0.001) or SAC (aOR = 0.5, p = 0.008; aIIR = 0.3, p = 0.01), being a female (aOR = 0.6, p = 0.004; aIIR = 0.3, p = 0.001), and having received deworming treatment the previous year (aOR = 0.4, p< 0.002; aIIR = 0.2, p<0.001) were associated with a lower prevalence and intensity of hookworm infection. Lower income (lowest quintile: aOR = 5.0, p<0.001, 2^nd quintile aOR = 3.6, p = 0.001 and 3^rd quintile aOR = 2.5, p = 0.02), being a farmer (aOR = 1.8, p = 0.02), medium population density (aOR = 2.6, p = 0.01), and open defecation (aOR = 0.5, p = 0.04) were associated with a higher prevalence of hookworm infection. Lower education—no education, primary or secondary school- (aIIR = 40.1, p = 0.01; aIIR = 30.9, p = 0.02; aIIR = 19.3, p = 0.04, respectively), farming (aIIR = 3.9, p = 0.002), natural flooring (aIIR = 0.2, p = 0.06), peri-urban settings (aIIR = 6.2, 95%CI 1.82–20.90, p = 0.003), and unimproved water source more than 30 minutes from the household (aIIR = 13.5, p = 0.02) were associated with a higher intensity of hookworm infection. Improved and unshared toilet was associated with lower intensity of hookworm infections (aIIR = 0.2, p = 0.01). SAC had a higher odds of Ascaris lumbricoides infection than adults (aOR = 2.0, p = 0.01) and females had a lower odds of infection (aOR = 0.5, p = 0.02).ConclusionHookworm spp. are the most prevalent STH in Comé, with a persistent reservoir in adults that is not addressed by current control measures based on school MDA. Expanding MDA to target adults and PSAC is necessary to substantially impact population prevalence, particularly for hookworm.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03014167","term_id":"NCT03014167"}}NCT03014167.     

Association of Gestational Age at Birth with Reasons for Subsequent Hospitalisation: 18 Years of Follow-Up in a Western Australian Population Study

Background

Preterm infants are at a higher risk of hospitalisation following discharge from the hospital after birth. The reasons for rehospitalisation and the association with gestational age are not well understood.

Methods

This was a retrospective birth cohort study of all live, singleton infants born in Western Australia between 1^st January 1980 and 31^st December 2010, followed to 18 years of age. Risks of rehospitalisation following birth discharge by principal diagnoses were compared for gestational age categories (<32, 32–33, 34–36, 37–38 weeks) and term births (39–41weeks). Causes of hospitalisations at various gestational age categories were identified using ICD-based discharge diagnostic codes.

Results

Risk of rehospitalisation was inversely correlated with gestational age. Growth-related concerns were the main causes for rehospitalisation in the neonatal period (<1 month of age) for all gestational ages. Infection was the most common reason for hospitalisation from 29 days to 1 year of age, and up to 5 years of age. Injury-related hospitalisations increased in prevalence from 5 years to 18 years of age. Risk of rehospitalisation was higher for all preterm infants for most causes.

Conclusions

The highest risks of rehospitalisation were for infection related causes for most GA categories. Compared with full term born infants, those born at shorter GA remain vulnerable to subsequent hospitalisation for a variety of causes up until 18 years of age.     

Lifestyle Factors,Medication Use and Risk for Ischaemic Heart Disease Hospitalisation: A Longitudinal Population-Based Study

Background

Lifestyle factors have been implicated in ischaemic heart disease (IHD) development however a limited number of longitudinal studies report results stratified by cardio-protective medication use.

Purpose

This study investigated the influence of self-reported lifestyle factors on hospitalisation for IHD, stratified by blood pressure and/or lipid-lowering therapy.

Methods

A population-based cohort of 14,890 participants aged 45+ years and IHD-free was identified from the Western Australian Health and wellbeing Surveillance System (2004 to 2010 inclusive), and linked with hospital administrative data. Adjusted hazard ratios for future IHD-hospitalisation were estimated using Cox regression.

Results

Current smokers remained at higher risk for IHD-hospitalisation (adjusted HR=1.57; 95% CI: 1.22-2.03) after adjustment for medication use, as did those considered overweight (BMI=25-29 kg/m²; adjusted HR=1.28; 95% CI: 1.04-1.57) or obese (BMI of ≥30kg/m²; adjusted HR=1.31; 95% CI: 1.03-1.66). Weekly leisure-time physical activity (LTPA) of 150 minutes or more and daily intake of 3 or more fruit/vegetable servings reduced risk by 21% (95% CI: 0.64-0.97) and 26% (95% CI: 0.58-0.96) respectively. Benefits of LTPA appeared greatest in those on blood pressure lowering medication (adjusted HR=0.50; 95% CI: 0.31-0.82 [for LTPA<150 mins], adjusted HR=0.64; 95% CI: 0.42-0.96 [for LTPA>=150 mins]). IHD risk in smokers was most pronounced in those taking neither medication (adjusted HR=2.00; 95% CI: 1.41-2.83).

Conclusion

This study confirms the contribution of previously reported lifestyle factors towards IHD hospitalisation, even after adjustment for antihypertensive and lipid-lowering medication use. Medication stratified results suggest that IHD risks related to LTPA and smoking may differ according to medication use.