Correction: "We know about schistosomiasis but we know nothing about FGS": A qualitative assessment of knowledge gaps about female genital schistosomiasis among communities living in Schistosoma haematobium endemic districts of Zanzibar and Northwestern Tanzania.

[This corrects the article DOI: 10.1371/journal.pntd.0009789.].

Predicting no-show appointments in a pediatric hospital in Chile using machine learning.

The Chilean public health system serves 74% of the country's population, and 19% of medical appointments are missed on average because of no-shows. The national goal is 15%, which coincides with the average no-show rate reported in the private healthcare system. Our case study, Doctor Luis Calvo Mackenna Hospital, is a public high-complexity pediatric hospital and teaching center in Santiago, Chile. Historically, it has had high no-show rates, up to 29% in certain medical specialties. Using machine learning algorithms to predict no-shows of pediatric patients in terms of demographic, social, and historical variables. To propose and evaluate metrics to assess these models, accounting for the cost-effective impact of possible intervention strategies to reduce no-shows. We analyze the relationship between a no-show and demographic, social, and historical variables, between 2015 and 2018, through the following traditional machine learning algorithms: Random Forest, Logistic Regression, Support Vector Machines, AdaBoost and algorithms to alleviate the problem of class imbalance, such as RUS Boost, Balanced Random Forest, Balanced Bagging and Easy Ensemble. These class imbalances arise from the relatively low number of no-shows to the total number of appointments. Instead of the default thresholds used by each method, we computed alternative ones via the minimization of a weighted average of type I and II errors based on cost-effectiveness criteria. 20.4% of the 395,963 appointments considered presented no-shows, with ophthalmology showing the highest rate among specialties at 29.1%. Patients in the most deprived socioeconomic group according to their insurance type and commune of residence and those in their second infancy had the highest no-show rate. The history of non-attendance is strongly related to future no-shows. An 8-week experimental design measured a decrease in no-shows of 10.3 percentage points when using our reminder strategy compared to a control group. Among the variables analyzed, those related to patients' historical behavior, the reservation delay from the creation of the appointment, and variables that can be associated with the most disadvantaged socioeconomic group, are the most relevant to predict a no-show. Moreover, the introduction of new cost-effective metrics significantly impacts the validity of our prediction models. Using a prototype to call patients with the highest risk of no-shows resulted in a noticeable decrease in the overall no-show rate.

Healthcare Workers' Low Knowledge of Female Genital Schistosomiasis and Proposed Interventions to Prevent, Control, and Manage the Disease in Zanzibar.

Objectives: This study was conducted to explore healthcare workers' knowledge of female genital schistosomiasis (FGS) and describe proposed interventions to raise awareness about FGS and strengthen healthcare facilities' capacity to manage FGS cases. Methods: We conducted four cross-sectional focus group discussions and 16 key informant interviews with purposively selected healthcare workers in Zanzibar. Discussions and interviews were digitally recorded, transcribed, and analyzed using NVivo software. Results: Most participants had limited or no knowledge of FGS and lacked skills for managing it. They confused FGS with urogenital schistosomiasis and thought it was sexually transmitted. A few participants knew about FGS and associated it with Human Immunodeficiency Virus (HIV), ectopic pregnancy, cervical cancer, and infertility. To prevent and control FGS, participants proposed interventions targeting communities (including community-based health education) and the healthcare system (including training healthcare workers on FGS). Conclusion: Healthcare workers lacked knowledge of and skills for managing FGS. Besides, healthcare facilities had no diagnostic capacity to manage FGS. Along with on-going interventions to break S. haematobium transmission and eventually eliminate urogenital schistosomiasis in Zanzibar, we recommend training healthcare workers on FGS and equip healthcare facilities with medical equipment and supplies for managing FGS.

A Cluster-Randomized Trial of Traditional Healer-Delivered Counseling and Rapid HIV Testing in Tanzania.

Collaborations with traditional healers have been proposed to improve HIV testing uptake. We hypothesized that healer-delivered HIV testing would improve HIV testing uptake, compared with referral to clinic-based HIV testing. We conducted a cluster randomized trial to determine the effectiveness of traditional healers delivering counseling and HIV testing in Mwanza, Tanzania (ClinicalTrials.gov NCT#04071873). Intervention arm healers provided counseling and offered point-of-care HIV tests to adult clients of unknown HIV serostatus. Control arm healers provided referral for clinic-based testing. Primary outcome was receipt of an HIV test within 90 days of enrollment. Secondary outcomes were new HIV diagnosis and linkage to care. In the intervention, 100 clients (100%) received an HIV test, compared with 73 (73%) of control participants (p < 0.001). Two intervention arm participants (2%) had a new diagnosis compared with zero in the control arm (p = 0.50). Engaging traditional healers might provide a culturally concordant opportunity to improve HIV testing uptake.

"Female genital schistosomiasis is a sexually transmitted disease": Gaps in healthcare workers' knowledge about female genital schistosomiasis in Tanzania.

Female Genital Schistosomiasis is a gynecological disease that is a complication of parasitic Schistosoma haematobium infection and affects at least 40 million girls and women, mostly in sub-Saharan Africa. Little is known about how healthcare workers in endemic areas perceive and manage (diagnose and treat) Female Genital Schistosomiasis. We conducted cross-sectional focus group discussions and key informant interviews among healthcare workers in northwestern Tanzania. Healthcare workers, particularly those working in areas where S. haematobium is highly endemic, were purposively sampled to participate in the study. Discussions and interviews were digitally recorded, transcribed, and analyzed using NVivo version 12. Most healthcare workers lacked knowledge and skills to manage Female Genital Schistosomiasis. They also had multiple misconceptions about its aetiology, modes of transmission, symptoms, and management. Healthcare workers did not consider Female Genital Schistosomiasis in differential diagnoses of women presenting with gynecologic symptoms except sometimes in patients who did not respond to the initial therapy for sexually transmitted infections. Healthcare facilities had limited capacity to manage Female Genital Schistosomiasis. Our findings show critical gaps in both the knowledge of healthcare workers to manage Female Genital Schistosomiasis and in the capacity of healthcare facilities to manage it. To fill these gaps, two urgent needs must be fulfilled: first, training healthcare workers (particularly those working in schistosomiasis-endemic settings) on Female Genital Schistosomiasis, and second, stocking healthcare facilities with necessary medical equipment and supplies for managing this disease.

Understanding the role of traditional healers in the HIV care cascade: Findings from a qualitative study among stakeholders in Mwanza, Tanzania.

Tanzania is HIV-endemic, with 5% prevalence. However, less than half of Tanzanians are aware of their HIV status, and only 75% of adult Tanzanians living with HIV are on antiretroviral therapy (ART). Informal healthcare providers, such as traditional healers, frequently serve as the first line of healthcare in Tanzania. How traditional healers interact with people living with HIV (PLWH) remains unknown. This study sought to understand gaps in HIV care and explore how traditional healers interface with PLWH along the HIV care cascade. We conducted a qualitative study in Mwanza, Tanzania, between November 2019 and May 2020. We invited 15 traditional healers, 15 clients of traditional healers, 15 biomedical healthcare facility staff, and 15 PLWH to participate in a single qualitative interview. Two community focus groups were held with eight male and eight female participants. Participants were 18 years of age or older. Individual experiences with traditional healers and biomedical healthcare facilities, as well as perceptions of traditional healers with respect to HIV care, were explored through interviews. Using a content-analysis approach, codes were grouped into a framework that characterized how traditional healers engage with PLWH throughout the HIV care cascade. PLWH engaged with traditional healers throughout the HIV care cascade, from pre- to post-HIV diagnosis. Traditional healers were described in some cases as facilitating HIV testing, while others were described as delaying testing by providing traditional treatments for HIV symptoms. Traditional medications were frequently used concurrently with ARTs by PLWH. There was concern that healers contributed to ART nonadherence as some PLWH used traditional therapies in search of a "cure" for HIV. Our findings suggest that traditional healers interact with PLWH throughout the HIV care continuum and that collaboration between traditional healers and biomedical healthcare professionals and facilities is needed to improve HIV treatment outcomes.

"We know about schistosomiasis but we know nothing about FGS": A qualitative assessment of knowledge gaps about female genital schistosomiasis among communities living in Schistosoma haematobium endemic districts of Zanzibar and Northwestern Tanzania.

BACKGROUND: Schistosoma haematobium causes urogenital schistosomiasis and is widely distributed in Tanzania. In girls and women, the parasite can cause Female Genital Schistosomiasis (FGS), a gynecological manifestation of schistosomiasis that is highly neglected and overlooked by public health professionals and policy makers. This study explored community members' knowledge, attitudes and perceptions (KAP) on and health seeking behavior for FGS. METHODS/PRINCIPAL FINDINGS: Using qualitative research methods-including 40 Focus Group Discussions (FGDs) and 37 Key Informant Interviews (KIIs)-we collected data from 414 participants (Males n = 204 [49.3%] and Females n = 210 [50.7%]). The study engaged 153 participants from Zanzibar and 261 participants from northwestern Tanzania and was conducted in twelve (12) purposively selected districts (7 districts in Zanzibar and 5 districts in northwestern Tanzania). Most participants were aware of urogenital schistosomiasis. Children were reported as the most affected group and blood in urine was noted as a common symptom especially in boys. Adults were also noted as a risk group due to their involvement in activities like paddy farming that expose them to infection. Most participants lacked knowledge of FGS and acknowledged having no knowledge that urogenital schistosomiasis can affect the female reproductive system. A number of misconceptions on the symptoms of FGS and how it is transmitted were noted. Adolescent girls and women presenting with FGS related symptoms were reported to be stigmatized, perceived as having a sexually transmitted infection (STI), and sometimes labeled as "prostitutes". Health seeking behavior for FGS included a combination of traditional medicine, self-treatment and modern medicine. CONCLUSION/SIGNIFICANCE: Community members living in two very different areas of Tanzania exhibited major, similar gaps in knowledge about FGS. Our data illustrate a critical need for the national control program to integrate public health education about FGS during the implementation of school- and community-based mass drug administration (MDA) programs and the improvement of water, sanitation and hygiene (WASH) facilities.

The incidence of psoriasis in Chile: an analysis of the National Waiting List Repository.

BACKGROUND: Psoriasis is a serious and chronic noncommunicable disease. However, the fundamental measure of disease occurrence, the incidence, has been scarcely reported globally. There are no previous studies of psoriasis incidence in Latin America. AIM: To estimate the incidence rates of psoriasis in Chile during 2016 and 2017 using an administrative database, the Waiting List Repository. METHODS: We examined referrals of psoriasis at onset, made by physicians to dermatologists, evaluated the agreement of diagnosis, and estimated the incidence of the disease considering the eligible population at risk. RESULTS: In most cases, the referrals corresponded to incident cases of psoriasis (73.3%; 95% CI: 66.6-79.2). The national incidence rates of psoriasis were 22.1 (95% CI: 21.1-23.1) and 22.7 (95% CI: 21.8-23.6) per 100 000 person-years in 2016 and 2017, respectively. The most common type of psoriasis was the late-onset type. We observed a high variation in the figures throughout the country, with a range from 0.75 (95% CI: 0.3-1.5) per 100 000 person-years in the Metropolitan region to 164.9 (95% CI: 138.6-195.1) per 100 000 person-years in the Aysen region. CONCLUSION: We describe for the first time the incidence of psoriasis in a Latin American country. Our findings could potentially guide collaborations to improve our global understanding of psoriasis in Latin America.

Relationship between tumor-associated immune infiltrate and p16 staining over clinicopathological features in acral lentiginous melanoma.

PURPOSE: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. MATERIALS AND METHODS: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. RESULTS: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. CONCLUSIONS: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .

Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America

Purpose. Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. Methods. All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed. Results. 537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I-II patients had a median OS of 5.3 (95% CI 4.3-6.2) for ALM and 9.2 (95% CI 5.0-7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001). Conclusions. ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM (AU)

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Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America.

PURPOSE: Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. METHODS: All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed. RESULTS: 537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I-II patients had a median OS of 5.3 (95% CI 4.3-6.2) for ALM and 9.2 (95% CI 5.0-7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001). CONCLUSIONS: ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.

Postnatal fish oil supplementation in high-risk infants to prevent allergy: randomized controlled trial.

BACKGROUND AND OBJECTIVE: Relative deficiency of dietary omega 3 polyunsaturated fatty acids (n-3 PUFA) has been implicated in the rising allergy prevalence in Westernized countries. Fish oil supplementation may provide an intervention strategy for primary allergy prevention. The objective of this study was to assess the effect of fish oil n-3 PUFA supplementation from birth to 6 months of age on infant allergic disease. METHODS: In a double-blind randomized controlled trial, 420 infants at high atopic risk received a daily supplement of fish oil containing 280 mg docosahexaenoic acid and 110 mg eicosapentaenoic acid or a control (olive oil), from birth to age 6 months. PUFA levels were measured in 6-month-old infants' erythrocytes and plasma and their mothers' breast milk. Eczema, food allergy, asthma and sensitization were assessed in 323 infants for whom clinical follow-up was completed at 12 months of age. RESULTS: At 6 months of age, infant docosahexaenoic acid and eicosapentaenoic acid levels were significantly higher (both P < .05) and erythrocyte arachidonic acid levels were lower (P = .003) in the fish oil group. Although n-3 PUFA levels at 6 months were associated with lower risk of eczema (P = .033) and recurrent wheeze (P = .027), the association with eczema was not significant after multiple comparisons and there was no effect of the intervention per se on the primary study outcomes. Specifically, between-group comparisons revealed no differences in the occurrence of allergic outcomes including sensitization, eczema, asthma, or food allergy. CONCLUSIONS: Postnatal fish oil supplementation improved infant n-3 status but did not prevent childhood allergic disease.

Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease.

BACKGROUND: Previous studies have demonstrated that reduced T-cell protein kinase C zeta (PKCζ) expression is associated with allergy development in infants born to atopic mothers. This study examined whether this relationship extends to a general population and addressed the basis for the association. METHODS: A flow cytometry assay was developed for the measurement of T-cell PKCζ levels in PBMC, cord blood mononuclear cell and whole blood. Cord blood T-cell PKCζ levels were measured in 135 neonates, and allergic disease was evaluated by skin prick test and clinical examination at 12 months of age. RESULTS: Allergic children (particularly those with eczema) had significantly lower neonatal T-cell PKCζ expression than nonallergic children (P < 0.001). PKCζ levels predicted allergic disease with optimal specificity of 86% and sensitivity of 54%. The sensitivity was increased in the children of allergic mothers, who had significantly lower PKC levels than the children of nonallergic mothers. Cord blood PKCζ levels did not affect T-cell maturation in culture as assessed by CD45RA/RO expression, but low PKCζ expression was associated with reduced capacity for IFNγ production by matured T cells. Low cord blood PKC expression was further associated with increased IL-13 responses at 6 months. CONCLUSIONS: The findings suggest a potential role for the use of PKCζ levels in cord blood T cells as a presymptomatic test to predict allergy risk in children, particularly offspring of allergic mothers, and that the basis of this relationship is related to cytokine patterns in mature T cells.

Fish oil supplementation in early infancy modulates developing infant immune responses.

BACKGROUND: Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema. OBJECTIVE: To examine the effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease. METHODS: In a double-blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil [containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA-DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age. RESULTS: DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P < 0.05). Infants in the fish oil group had significantly lower IL-13 responses (P = 0.036) to house dust mite (HDM) and higher IFNγ (P = 0.035) and TNF (P = 0.017) responses to phytohaemaglutinin (PHA). Infants with relatively high DHA levels had lower Th2 responses to allergens including lower IL-13 to ß-lactoglobulin (BLG) (P = 0.020), and lower IL-5 to BLG (P = 0.045). CONCLUSIONS AND CLINICAL RELEVANCE: Postnatal fish oil supplementation increased infant n-3 polyunsaturated fatty acid (PUFA) levels and associated with lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n-3 PUFA having immunomodulatory properties that are potentially allergy-protective.

Determinants of DHA levels in early infancy: differential effects of breast milk and direct fish oil supplementation.

INTRODUCTION: Although omega (n)-3 long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), intakes are important during infancy, the optimal method of increasing infant status remains unclear. We hypothesized that high-dose infant fish oil supplementation would have greater relative effects upon n-3 LCPUFA status at six months of age than breast milk fatty acids. PATIENTS AND METHODS: Infants (n=420) were supplemented daily from birth to six months with fish oil or placebo. In a subset of infants, LCPUFA levels were measured in cord blood, breast milk and in infant blood at 6 months. RESULTS: DHA levels increased in the fish oil group relative to placebo (p<05). Breast milk DHA was the strongest predictor of infant erythrocyte DHA levels (p=<001). This remained significant after adjustment for cord blood DHA, supplementation group and adherence. CONCLUSION: In this cohort, breast milk DHA was a greater determinant of infant erythrocyte n-3 LCPUFA status, than direct supplementation with fish oil.

The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood.

BACKGROUND: Dietary changes may epigenetically modify fetal gene expression during critical periods of development to potentially influence disease susceptibility. This study examined whether maternal and/or fetal folate status in pregnancy is associated with infant allergic outcomes. METHODS: Pregnant women (n=628) were recruited in the last trimester of pregnancy. Folate status determined by both food frequency questionnaires and folate levels in maternal and cord blood serum was examined in relation to infant allergic outcomes at 1 year of age (n=484). RESULTS: Infants who developed allergic disease (namely eczema) did not show any differences in cord blood or maternal folate levels compared with children without disease. Although maternal folate intake from foods was also not different, folate derived from supplements was higher (P=0.017) in children with subsequent eczema. Furthermore, infants exposed to >500 µg folic acid/day as a supplement in utero were more likely to develop eczema than those taking <200 µg/day (OR [odds ratio] =1.85; 95% CI 1.14-3.02; P=0.013), remaining significant after adjustment for maternal allergy and other confounders. There was a nonlinear relationship between cord blood folate and sensitization, with folate levels <50 nmol/l (OR=3.02; 95% CI 1.16-7.87; P=0.024) and >75 nmol/l (OR=3.59; 95% CI 1.40-9.20; P=0.008) associated with greater sensitization risk than levels between 50 and 75 nmol/l. CONCLUSION: Fetal levels between 50 and 75 nmol/l appeared optimal for minimizing sensitization. While folate taken as a supplement in higher doses during the third trimester was associated with eczema, there was no effect on other allergic outcomes including sensitization. Further studies are needed to determine the significance of this.

The Infant Fish Oil Supplementation Study (IFOS): design and research protocol of a double-blind, randomised controlled n--3 LCPUFA intervention trial in term infants.

STUDY DESIGN: The Infant Fish Oil Supplementation Study is a double-blind randomised controlled trial investigating whether the incidence of allergic disease can be reduced and developmental outcomes enhanced through supplementation with omega-3 fatty acids. Infants at high risk of developing allergic disease will be randomised to receive either fish oil or olive oil supplements until 6 months of age and followed up at six postnatal clinic visits to assess allergy outcomes and infant neurodevelopment. INTERVENTION: Study groups to consist of a treatment group allocated to receive 650 mg of fish oil daily (250-280 mg docosahexaenoic acid and at least 60 mg eicosapentaenoic acid and a placebo group (olive oil) from birth to 6 months of age. OUTCOMES: Allergy outcomes will be assessed by clinical history, clinical assessments and allergen skin prick tests at the 12, 30 and 60 month visits. Neurodevelopmental assessments to be conducted at 18 months, and language questionnaires at 12, 18 and 30 months. Samples will be collected from mothers antenatally, from infants at birth, and at clinic visits from 6 months onwards for immunological assessments. Fatty acid composition to be measured in erythrocytes and plasma (at birth and after the supplementation period) to assess the effect of the intervention on fatty acid status. Information on medical history, diet and other lifestyle factors at an antenatal clinic visit and postnatal clinic visits will also be collected. CONCLUSION: This study is designed to examine clinically relevant effects of a novel, non-invasive and potentially low cost approach to reduce the incidence of allergic disease and facilitate neurodevelopment during early childhood.

The effects of Mycobacteria vaccae derivative on allergen-specific responses in children with atopic dermatitis.

The capacity of microbial products to inhibit allergic inflammation make them logical candidates for novel therapies in allergic diseases such as atopic dermatitis. To assess the effects of intradermal Mycobacterium vaccae derivative on allergen-specific immune responses in children with moderate to severe atopic dermatitis. Peripheral blood mononuclear cells were isolated from children aged 5-16 years who received intradermal injections of M. vaccae derivative AVAC(TM) (n = 26) or placebo (n = 34) three times at 2-weekly intervals, weeks 0, 2 and 4. Cytokine [interleukin (IL)-13, interferon (IFN)-γ and IL-10] responses to allergen [house dust mite (HDM)], mitogen [phytohaemagglutinin (PHA)], Staphylococcal enterotoxin B (SEB) and Toll-like receptor (TLR) ligands were assessed. At week 8 (1 month after all injections given) children in the AVAC group showed a significant increase in IL-10 (P = 0·009), T helper type 1 (Th1) IFN-γ (P = 0·017) and Th2 IL-13 (P = 0·004) responses to HDM compared with baseline (week 0). There were no significant changes in any cytokine production in the placebo. HDM-specific IL-10 responses remained significantly higher (P = 0·014) than at baseline in the AVAC group by week 12; however, the HDM-specific IL-13 and IFN-γ responses were no longer significantly different from baseline. IL-13 (r = 0·46, P < 0·001) and IL-10 (r = 0·27, P = 0·044) responses to HDM were correlated with total immunoglobulin E but not with disease severity. There were no effects of AVAC on mitogen, SEB, TLR-2- or TLR-4-mediated responses. This M. vaccae derivative appeared to modulate responses to HDM selectively, suggesting the capacity for in vivo effects on allergen-specific immune responses.

Allergic women show reduced T helper type 1 alloresponses to fetal human leucocyte antigen mismatch during pregnancy.

Low-level alloreactivity between mother and fetus may provide stimulation for fetal T helper type 1 (Th1) cell immune maturation. This study explored the effects of human leucocyte antigen (HLA) mismatch on materno-fetal interactions detected as cytokine responses and lymphoproliferation in mixed lymphocyte reactions, and whether this was altered in allergic women (n = 62) who have a Th2 propensity compared with non-allergic women (n = 65). HLA-DRbeta1 mismatch was associated with significantly increased Th1 interferon (IFN)-gamma, Th2 interleukin (IL)-13 and lymphoproliferative responses by both mothers and fetuses. Allergic women showed significantly lower IFN-gamma Th1 production in response to HLA-DRbeta1 mismatch. The infants of these women also showed significantly lower IL-10 and lower IFN-gamma production relative to IL-13. Both HLA-DRbeta1 mismatch and maternal allergy had significant independent effects on maternal IFN-gamma Th1 responses. Maternal allergy modifies HLA-mediated alloreactivity between the mother and the fetus, reducing Th1 activation. This may affect the cytokine milieu at the materno-fetal interface and could be implicated in the attenuated Th1 responses observed commonly in infants of atopic mothers.

Pregnancy IFN-gamma responses to foetal alloantigens are altered by maternal allergy and gravidity status.

BACKGROUND: During pregnancy, variations in maternal-foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies. METHODS: For this cohort study, peripheral blood was collected from allergic (n = 69) and nonallergic (n = 63) pregnant women at 20, 30, 36-week gestation and 6-week postpartum (pp). Cord blood was collected at delivery. Mixed lymphocyte reactions were used to measure maternal cytokine responses [interleukin-6 (IL-6), IL-10, IL-13 and (interferon-gamma) IFN-gamma] at each time point towards foetal mononuclear cells. RESULTS: Maternal cytokine responses during pregnancy (20, 30 and 36 weeks) were suppressed compared to the responses at 6-week pp. The ratio of maternal IFN-gamma/IL-13 and IFN-gamma/IL-10 responses were lower during pregnancy. Allergic mothers had lower IFN-gamma responses at each time-point during pregnancy with the greatest difference in responses observed at 36-week gestation. When allergic and nonallergic women were further stratified by gravidity group, IFN-gamma responses of allergic multigravid mothers were significantly lower than nonallergic multigravid mothers during pregnancy. CONCLUSIONS: During normal pregnancy, peripheral T-cell cytokine responses to foetal alloantigens may be altered by both allergic status of the mother and previous pregnancies. These factors could influence the cytokine milieu experienced by the foetus and will be further explored in the development of allergic disease during early life.