Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy

Background

Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described.

Methods

Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction.

Results

RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011–2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants.

Conclusions

RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.     

The Impact of Repeated Rounds of Mass Drug Administration with Diethylcarbamazine Plus Albendazole on Bancroftian Filariasis in Papua New Guinea

Background

This study employed various monitoring methods to assess the impact of repeated rounds of mass drug administration (MDA) on bancroftian filariasis in Papua New Guinea, which has the largest filariasis problem in the Pacific region.

Methodology/Principal Findings

Residents of rural villages near Madang were studied prior to and one year after each of three rounds of MDA with diethylcarbamazine plus albendazole administered per World Health Organization (WHO) guidelines. The mean MDA compliance rate was 72.9%. Three rounds of MDA decreased microfilaremia rates (Mf, 1 ml night blood by filter) from 18.6% pre-MDA to 1.3% after the third MDA (a 94% decrease). Mf clearance rates in infected persons were 71%, 90.7%, and 98.1% after 1, 2, and 3 rounds of MDA. Rates of filarial antigenemia assessed by card test (a marker for adult worm infection) decreased from 47.5% to 17.1% (a 64% decrease) after 3 rounds of MDA. The filarial antibody rate (IgG₄ antibodies to Bm14, an indicator of filarial infection status and/or exposure to mosquito-borne infective larvae) decreased from 59.3% to 25.1% (a 54.6% decrease). Mf, antigen, and antibody rates decreased more rapidly in children <11 years of age (by 100%, 84.2%, and 76.8%, respectively) relative to older individuals, perhaps reflecting their lighter infections and shorter durations of exposure/infection prior to MDA. Incidence rates for microfilaremia, filarial antigenemia, and antifilarial antibodies also decreased significantly after MDA. Filarial DNA rates in Anopheles punctulatus mosquitoes that had recently taken a blood meal decreased from 15.1% to 1.0% (a 92.3% decrease).

Conclusions/Significance

MDA had dramatic effects on all filariasis parameters in the study area and also reduced incidence rates. Follow-up studies will be needed to determine whether residual infection rates in residents of these villages are sufficient to support sustained transmission by the An. punctulatus vector. Lymphatic filariasis elimination should be feasible in Papua New Guinea if MDA can be effectively delivered to endemic populations.     

Impact of Pregnancy-Associated Malaria on Infant Malaria Infection in Southern Benin

Background

Infants of mothers with placental Plasmodium falciparum infections at delivery are themselves more susceptible to malaria attacks or to infection in early life.

Methodology/ Principal Findings

To assess the impact of either the timing or the number of pregnancy-associated malaria (PAM) infections on the incidence of parasitemia or malaria attacks in infancy, we followed 218 mothers through pregnancy (monthly visits) up to delivery and their infants from birth to 12 months of age (fortnightly visits), collecting detailed clinical and parasitological data. After adjustment on location, mother’s age, birth season, bed net use, and placental malaria, infants born to a mother with PAM during the third trimester of pregnancy had a significantly increased risk of infection (OR [95% CI]: 4.2 [1.6; 10.5], p = 0.003) or of malaria attack (4.6 [1.7; 12.5], p = 0.003). PAM during the first and second trimesters had no such impact. Similarly significant results were found for the effect of the overall number of PAM episodes on the time to first parasitemia and first malaria attack (HR [95% CI]: 2.95 [1.58; 5.50], p = 0.001 and 3.19 [1.59; 6.38], p = 0.001) respectively.

Conclusions/ Significance

This study highlights the importance of protecting newborns by preventing repeated episodes of PAM in their mothers.     

Trends in All-Cause Mortality across Gestational Age in Days for Children Born at Term

Background

Term birth is a gestational age from 259 days to 293 days. However trends in mortality according to gestational ages in days have not yet been described in this time period.

Methods and Findings

Based on nation-wide registries, we conducted a population-based cohort study among all children born at term in Denmark from 1997 to 2004 to estimate differences in mortality across gestational ages in days among singletons born at term. We studied early-neonatal mortality, neonatal mortality, infant mortality, and five-year mortality. Children were followed from birth up to the last day of the defined mortality period or December 31, 2009. A total of 360,375 singletons born between 259 and 293 days of gestation were included in the study. Mortality decreased with increasing gestational age in days and the highest mortality was observed among children born at 37 week of gestation. A similar pattern was observed when analyses were restricted to children born to by mothers without pregnancy complications.

Conclusions

This study demonstrates heterogeneity in mortality rates even among singletons born at term. The highest mortality was observed among children born 37 weeks of gestation, which call for cautions when inducing labor in term pregnancies just reaching 37 weeks of gestation. The findings support that 37 weeks of gestation should be defined as early term.     

Risk Factors and Screening for Trypanosoma cruzi Infection of Dutch Blood Donors

Background

Blood donors unaware of Trypanosoma cruzi infection may donate infectious blood. Risk factors and the presence of T. cruzi antibodies in at-risk Dutch blood donors were studied to assess whether specific blood safety measures are warranted in the Netherlands.

Methodology

Birth in a country endemic for Chagas disease (CEC), having a mother born in a CEC, or having resided for at least six continuous months in a CEC were considered risk factors for T. cruzi infection. From March through September 2013, risk factor questions were asked to all donors who volunteered to donate blood or blood components. Serum samples were collected from donors reporting one or more risk factors, and screened for IgG antibodies to T. cruzi by EIA.

Results

Risk factors for T. cruzi infection were reported by 1,426 of 227,278 donors (0.6%). Testing 1,333 at-risk donors, none (0.0%; 95%, CI 0.0–0.4%) was seroreactive for IgG antibodies to T. cruzi. A total of 472 donors were born in a CEC; 553 donors reported their mother being born in a CEC; and 1,121 donors reported a long-term stay in a CEC. The vast majority of reported risk factors were related to Suriname and Brazil. Overall, the participants resided for 7,694 years in CECs, which equals 2.8 million overnight stays. Of those, 1.9 million nights were spent in Suriname.

Conclusions/Significance

Asymptomatic T. cruzi infection appears to be extremely rare among Dutch blood donors. Blood safety interventions to mitigate the risk of T. cruzi transmission by transfusion would be highly cost-ineffective in the Netherlands, and are thus not required.     

Placental Microparticles and MicroRNAs in Pregnant Women with Plasmodium falciparum or HIV Infection

Background

During pregnancy, syncytiotrophoblast vesicles contribute to maternal tolerance towards the fetus, but also to pathologies such as pre-eclampsia. The aim of the study was to address whether Plasmodium falciparum and HIV infections in pregnancy affect the secretion, microRNA content and function of trophoblast microparticles.

Methods

Microparticles were isolated and characterized from 122 peripheral plasmas of Mozambican pregnant women, malaria- and/or HIV-infected and non-infected. Expression of placenta-related microRNAs in microparticles was analysed by qPCR and the effect of circulating microparticles on dendritic cells assessed by phenotype analysis and cytokine/chemokine measurement.

Results

Concentrations of total and trophoblast microparticles detected by flow cytometry were higher in HIV-positive (P = 0.005 and P = 0.030, respectively) compared to non-infected mothers, as well as in women delivering low birthweight newborns (P = 0.032 and P = 0.021, respectively). miR-517c was overexpressed in mothers with placental malaria (P = 0.034), compared to non-infected. Microparticles from HIV-positive induced a higher expression of MHCII (P = 0.021) and lower production of MCP1 (P = 0.008) than microparticles from non-infected women.

Conclusions

In summary, alterations in total and trophoblast microparticles associated with malaria and HIV in pregnant women may have an immunopathogenic role. The potential for placental-derived vesicles and microRNAs as biomarkers of adverse outcomes during pregnancy and malaria infection should be confirmed in future studies.     

Costs of Testing for Ocular Chlamydia trachomatis Infection Compared to Mass Drug Administration for Trachoma in The Gambia: Application of Results from the PRET Study

Background

Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥10% in children aged 1–9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds.

Methods

The implementation unit in PRET The Gambia was a census enumeration area (EA) of 600–800 people. Personnel, fuel, equipment, consumables, data entry and supervision costs were collected for census and treatment of a sample of EAs and for the examination, sampling and testing for Ct infection of 100 individuals within them. Programme costs and resource savings from testing and treatment strategies were inferred for the 102 EAs in the study area, and compared.

Results

Census costs were $103.24 per EA plus initial costs of $108.79. MDA with donated azithromycin cost $227.23 per EA. The mean cost of examining and testing 100 children was $796.90 per EA, with Ct testing kits costing $4.80 per result. A strategy of testing each EA for infection is more expensive than two annual rounds of MDA unless the kit cost is less than $1.38 per result. However stopping or deciding not to initiate treatment in the study area based on testing a sample of EAs for Ct infection (or examining children in a sample of EAs) creates savings relative to further unnecessary treatments.

Conclusion

Resources may be saved by using tests for chlamydial infection or clinical examination to determine that initial or subsequent rounds of MDA for trachoma are unnecessary.     

Association between Maternal Smoking during Pregnancy and Low Birthweight: Effects by Maternal Age

Background

Maternal smoking during pregnancy has been consistently related to low birthweight. However, older mothers, who are already at risk of giving birth to low birthweight infants, might be even more susceptible to the effects of maternal smoking. Therefore, this study aimed to examine the modified association between maternal smoking and low birthweight by maternal age.

Methods

Data were obtained from a questionnaire survey of all mothers of children born between 2004 and 2010 in Okinawa, Japan who underwent medical check-ups at age 3 months. Variables assessed were maternal smoking during pregnancy, maternal age, gestational age, parity, birth year, and complications during pregnancy. Stratified analyses were performed using a logistic regression model.

Results

In total, 92641 participants provided complete information on all variables. Over the 7 years studied, the proportion of mothers smoking during pregnancy decreased from 10.6% to 5.0%, while the prevalence of low birthweight did not change remarkably (around 10%). Maternal smoking was significantly associated with low birthweight in all age groups. The strength of the association increased with maternal age, both in crude and adjusted models.

Conclusions

Consistent with previous studies conducted in Western countries, this study demonstrates that maternal age has a modifying effect on the association between maternal smoking and birthweight. This finding suggests that specific education and health care programs for older smoking mothers are important to improve their foetal growth.     

Adolescent Pregnancy and Attained Height among Black South African Girls: Matched-Pair Prospective Study

Importance

The impact of adolescent pregnancy on offspring birth outcomes has been widely studied, but less is known about its impact on the growth of the young mother herself.

Objective

To determine the association between adolescent pregnancy and attained height.

Design

Prospective birth cohort study.

Setting

Cohort members followed from birth to age 20 y in Soweto, South Africa.

Participant

From among 840 Black females with sufficient data, we identified 54 matched pairs, in which a girl who became pregnant before the age of 17 years was matched with a girl who did not have a pregnancy by age 20 y. Pairs were matched on age at menarche and height-for-age z scores in the year before the case became pregnant (mean 15.0 y).

Main Outcome Measures

The two groups were compared with respect to attained height, measured at mean age 18.5 y.

Results

Mean age at conception was 15.9 years (range: 13.7 to 16.9 y). Mean height at matching was 159.4 cm in the adolescent pregnancy group and 159.3 cm in the comparison group (p = 0.3). Mean attained height was 160.4 cm in the adolescent pregnancy group and 160.3 cm in the comparison group (p = 0.7).

Conclusions

Among Black females in Soweto, South Africa, adolescent pregnancy was not associated with attained height.     

Peridomestic Infection as a Determining Factor of Dengue Transmission

Background

The study of endemic dengue transmission is essential for proposing alternatives to impact its burden. The traditional paradigm establishes that transmission starts around cases, but there are few studies that determine the risk.

Methods

To assess the association between the peridomestic dengue infection and the exposure to a dengue index case (IC), a cohort was carried out in two Mexican endemic communities. People cohabitating with IC or living within a 50-meter radius (exposed cohort) and subjects of areas with no ICs in a 200-meter radius (unexposed cohort) were included.

Results

Exposure was associated with DENV infection in cohabitants (PRa 3.55; 95%CI 2.37–5.31) or neighbors (PRa 1.82; 95%CI 1.29–2.58). Age, location, toilets with no direct water discharge, families with children younger than 5 and the House Index, were associated with infection. Families with older than 13 were associated with a decreased frequency. After a month since the IC fever onset, the infection incidence was not influenced by exposure to an IC or vector density; it was influenced by the local seasonal behavior of dengue and the age. Additionally, we found asymptomatic infections accounted for 60% and a greater age was a protective factor for the presence of symptoms (RR 0.98; 95%CI 0.97–0.99).

Conclusion

The evidence suggests that dengue endemic transmission in these locations is initially peridomestic, around an infected subject who may be asymptomatic due to demographic structure and endemicity, and it is influenced by other characteristics of the individual, the neighborhood and the location. Once the transmission chain has been established, dengue spreads in the community probably by the adults who, despite being the group with lower infection frequency, mostly suffer asymptomatic infections and have higher mobility. This scenario complicates the opportunity and the effectiveness of control programs and highlights the need to apply multiple measures for dengue control.     

Interactive Effects of Early Exclusive Breastfeeding and Pre-Pregnancy Maternal Weight Status on Young Children’s BMI – A Chinese Birth Cohort

Objectives

To assess if the maternal pre-pregnancy weight status (MPWS) alters the association of early infant feeding pattern (at one and third months) with infant body mass index (BMI) in the first two years of life.

Methods

A cohort of 2,220 neonates were recruited in a community-based study conducted in China. Body weight and length were measured at birth, at age one and two, with BMI calculated accordingly. The BMI z-scores (BMI-Z) were computed according to the World Health Organization Growth Standard (2006). Feeding patterns were classified as exclusive breastfeeding (EBF), mixed feeding (MF), and formula feeding (FF). General linear models (GLM) were employed to estimate main and interaction effects of EBF and MPWS on children’s BMI-Z.

Results

No main effect of MPWS was found on child BMI-Z at ages one and two, nor the feeding patterns. An interaction between MPWS and feeding patterns was detected (p<0.05). For children who were formula fed during the first month, those who were born to overweight/obesity (OW/OB) mothers had a significantly greater BMI-Z at ages one and two, compared with those with underweight/normal weight (UW/NW) mothers. FF children had greater BMI-Z at ages one and two compared with their EBF and MF counterparts, when they were born to OW/OB mothers.

Conclusions

Maternal pre-pregnancy weight control and early initiation of EBF for children are essential for healthy development in children’s BMI, hence the prevention of early life obesity.     

Occult Hepatitis B Virus Infection in Anti-HBs-Positive Infants Born to HBsAg-Positive Mothers in China

Objective

To investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey.

Methods

186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed.

Results

1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P = 0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region.

Conclusions

Occult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene.     

Study on Environmental Causes and SNPs of MTHFR,MS and CBS Genes Related to Congenital Heart Disease

Purpose

Congenital heart diseases (CHD) are among the most common birth defects in China. Environmental causes and folate metabolism changes may alter susceptibility to CHD. The aim of this study is to evaluate the relevant risk-factors of children with CHD and their mothers.

Methods

138 children with CHD and 207 normal children for controls were recruited. Their mothers were also enlisted in this study and interviewed following a questionnaire about their pregnant history and early pregnancy situation. Five single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS) and cystathionine β-synthase (CBS) of mothers and children were genotyped.

Results

There were significant differences in the gender of children, occupation of mothers, family history with CHD, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHD group and control group ( P < 0.05). Logistic regression analyses showed that after adjustment for above factors, MTHFR rs1801131 were significantly associated with their offspring CHD risk in mothers. Compared with the mothers whose MTHFR were rs1801131 AA and AC genotypes, the mothers who got a mutation of MTHFR rs1801131 CC genotypes had a 267% increase in risk of given birth of a CHD children (OR=3.67,95%CI=1.12-12.05). Meanwhile, MTHFR rs1801131 were significantly associated with CHD susceptibility in children (OR = 1.42, 95% CI = 1.00-2.44 in additive model).

Conclusions

Besides mothers’ social and fertility characteristics, our results suggested that the genetic variants in folate metabolism pathway might be one of the most related risk-factors of CHD. MTHFR rs1801131 were identified as loci in Chinese population that were involved in CHD.     

The impact of a filariasis control program on Lihir Island, Papua New Guinea

Background

Annual mass drug administration (MDA) over five years is the WHO''s recommended strategy to eliminate lymphatic filariasis (LF). Some experts, however, consider that longer periods of treatment might be necessary in certain high prevalence and transmission environments based upon past unsuccessful field experience and modelling.

Methodology/Principal Findings

To evaluate predictors of success in a LF control program we conducted an ecological study during a pre-existing MDA program. We studied 27 villages in Lihir Island, Papua New Guinea, from two areas with different infection rates before MDA. We undertook surveys to collect information on variables potentially having an influence on the outcome of the program, including epidemiological (baseline prevalence of infection, immigration rate), entomological (vector density) and operational (treatment coverage, vector control strategies) variables. The success in a village was defined using variables related to the infection (circulating filarial antigenemia prevalence <1%) and transmission (antigenemia prevalence <1 in 1000 children born since start of MDA). 8709 people were involved in the MDA program and average coverage rates were around 70%. The overall prevalence of filariasis fell from an initial 17.91% to 3.76% at round 5 (p<0.001). Viewed on a village by village basis, 12/27 (44%) villages achieved success. In multivariate analysis, low baseline prevalence was the only factor predicting both success in reducing infection rates (OR 19,26; CI 95% 1,12 to 331,82) and success in preventing new infections (OR 27,44; CI 95% 1,05 to 719,6). Low vector density and the use of an optimal vector control strategy were also associated with success in reducing infection rates, but this did not reach statistical significance.

Conclusions/Significance

Our results provide the data that supports the recommendation that high endemic areas may require longer duration MDA programs, or alternative control strategies.     

Alcohol Intake in Pregnancy Increases the Child's Risk of Atopic Dermatitis. The COPSAC Prospective Birth Cohort Study of a High Risk Population

Background

Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor in this development.

Objective

To analyze the impact of alcohol intake during pregnancy on the development of atopic dermatitis during the first 7 years of life.

Method

The COPSAC cohort is a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma, followed up for 7 years with scheduled visits every 6 months as well as visits for acute exacerbations of atopic dermatitis. Risk of atopic dermatitis from any alcohol consumption during pregnancy was analyzed as time-to-diagnosis and adjusted for known risk factors.

Results

177 of 411 children developed atopic dermatitis before age 7 years. We found a significant effect of alcohol intake during pregnancy on atopic dermatitis development (HR 1.44, 95% CI 1.05–1.99 p = 0.024). This conclusion was unaffected after adjustment for smoking, mother''s education and mother''s atopic dermatitis.

Limitations

The selection of a high-risk cohort, with all mothers suffering from asthma, and all children having a gestational age above 35 weeks with no congenital abnormality, systemic illness, or history of mechanical ventilation or lower airway infection.

Conclusion

Alcohol intake by pregnant women with a history of asthma, is significantly associated with an increased risk for the child for developing atopic dermatitis during the first 7 years of life.     

Association between Antibiotic Prescribing in Pregnancy and Cerebral Palsy or Epilepsy in Children Born at Term: A Cohort Study Using The Health Improvement Network

Background

Between 19%-44% pregnant women are prescribed antibiotics during pregnancy. A single, large randomised-controlled-trial (ORACLE Childhood Study II) found an increased risk of childhood cerebral palsy and possibly epilepsy following prophylactic antibiotic use in pregnant women with spontaneous preterm labour. We ascertained whether this outcome could be reproduced across the population of babies delivered at term and prospectively followed in primary-care using data from The Health Improvement Network.

Methods

We determined the risk of cerebral palsy or epilepsy in children whose mothers were prescribed antibiotics during pregnancy using a cohort of 195,909 women linked to their live, term-born, singleton children. We compared the effect of antibiotic class, number of courses and timing of prescribing in pregnancy. Analyses were adjusted for maternal risk factors (e.g. recorded infection, age, chronic conditions, social deprivation, smoking status). Children were followed until age seven years or cessation of registration with the primary-care practitioner.

Results

In total, 64,623 (33.0%) women were prescribed antibiotics in pregnancy and 1,170 (0.60%) children had records indicating cerebral palsy or epilepsy. Adjusted analyses showed no association between prescribing of any antibiotic and cerebral palsy or epilepsy (adj.HR 1.04, 95%CI 0.91–1.19). However, compared with penicillins, macrolides were associated with an increased risk of cerebral palsy or epilepsy (adj.HR 1.78, 95%CI 1.18–2.69; number needed to harm 153, 95%CI 71–671).

Conclusions

We found no overall association between antibiotic prescribing in pregnancy and cerebral palsy and/or epilepsy in childhood. However, our finding of an increased risk of cerebral palsy or epilepsy associated with macrolide prescribing in pregnancy adds to evidence that macrolide use is associated with serious harm.     

Brugia malayi Microfilariae Induce a Regulatory Monocyte/Macrophage Phenotype That Suppresses Innate and Adaptive Immune Responses

Background

Monocytes and macrophages contribute to the dysfunction of immune responses in human filariasis. During patent infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive.

Aim

To determine whether blood microfilariae directly act on blood monocytes and in vitro generated macrophages to induce a regulatory phenotype that interferes with innate and adaptive responses.

Methodology and principal findings

Monocytes and in vitro generated macrophages from filaria non-endemic normal donors were stimulated in vitro with Brugia malayi microfilarial (Mf) lysate. We could show that monocytes stimulated with Mf lysate develop a defined regulatory phenotype, characterised by expression of the immunoregulatory markers IL-10 and PD-L1. Significantly, this regulatory phenotype was recapitulated in monocytes from Wuchereria bancrofti asymptomatically infected patients but not patients with pathology or endemic normals. Monocytes from non-endemic donors stimulated with Mf lysate directly inhibited CD4⁺ T cell proliferation and cytokine production (IFN-γ, IL-13 and IL-10). IFN-γ responses were restored by neutralising IL-10 or PD-1. Furthermore, macrophages stimulated with Mf lysate expressed high levels of IL-10 and had suppressed phagocytic abilities. Finally Mf lysate applied during the differentiation of macrophages in vitro interfered with macrophage abilities to respond to subsequent LPS stimulation in a selective manner.

Conclusions and significance

Conclusively, our study demonstrates that Mf lysate stimulation of monocytes from healthy donors in vitro induces a regulatory phenotype, characterized by expression of PD-L1 and IL-10. This phenotype is directly reflected in monocytes from filarial patients with asymptomatic infection but not patients with pathology or endemic normals. We suggest that suppression of T cell functions typically seen in lymphatic filariasis is caused by microfilaria-modulated monocytes in an IL-10-dependent manner. Together with suppression of macrophage innate responses, this may contribute to the overall down-regulation of immune responses observed in asymptomatically infected patients.     

Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm

Objective

Magnetic resonance imaging (MRI) of the brain carried out during the neonatal period shows that 55–80% of extremely preterm infants display white matter diffuse excessive high signal intensity (DEHSI). Our aim was to study differences in developmental outcome at the age of 6.5 years in children born extremely preterm with and without DEHSI.

Study Design

This was a prospective cohort study of 83 children who were born in Stockholm, Sweden, between 2004 and 2007, born at gestational age of < 27 weeks + 0 days and who underwent an MRI scan of their brain at term equivalent age. The outcome measures at 6.5 years included testing 66 children with the modified Touwen neurology examination, the Movement Assessment Battery for Children 2, the Wechsler Intelligence Scale for Children—Fourth Edition, Beery Visual-motor Integration test—Sixth Edition, and the Strengths and Difficulties Questionnaire. Group-wise comparisons were done between children with and without DEHSI using Student t-test, Mann Whitney U test, Chi square test and regression analysis.

Results

DEHSI was detected in 39 (59%) of the 66 children who were assessed at 6.5 years. The presence of DEHSI was not associated with mild neurological dysfunction, scores on M-ABC assessment, cognition, visual-motor integration, or behavior at 6.5 years.

Conclusion

The presence of qualitatively defined DEHSI on neonatal MRI did not prove to be a useful predictor of long-term impairment in children born extremely preterm.