Gastrointestinal nematode infection during pregnancy and lactation enhances spatial reference memory and reduces indicators of anxiety-like behaviour in uninfected adult female mouse offspring.

Maternal bacterial and viral infections that induce neuroinflammation in the developing brain are associated with impaired cognitive function and increased anxiety in the offspring. In contrast, maternal infection with the immunoregulatory murine gastrointestinal (GI) nematode, Heligmosomoides bakeri, appears to benefit neurodevelopment as juvenile 2- and 3-week-old male and female offspring had enhanced spatial memory, which may be due to a Th2/Treg biased neuroimmune environment. Here, the impact of maternal H. bakeri infection during pregnancy and lactation on the spatial and anxiety-like behaviours of adult, 3-month-old uninfected male and female offspring was explored for the first time. It was observed that adult female offspring of H. bakeri-infected dams had enhanced spatial reference memory and reduced anxiety-like behaviour compared to females of uninfected dams. These effects were not observed in adult male offspring. Thus, the positive influence of a maternal GI nematode infection on spatial memory of juvenile offspring persists in adult female offspring.

Parasite load, rather than parasite presence, decreases upstream movement in Trinidadian guppies Poecilia reticulata.

Several factors influence whether an organism remains in its local habitat. Parasites can, for example, influence host movement by impacting their behavior, physiology, and morphology. In rivers, fish that swim efficiently against the current are able to maintain their position without being displaced downstream, a behavior referred to as positive rheotaxis. We hypothesized that both the presence and number of ectoparasites on a host would affect the ability of fish to avoid downstream displacement and thus prevent them from remaining in their habitat. We used the guppy-Gyrodactylus host-ectoparasite model to test whether parasite presence and parasite load had an effect on fish rheotaxis. We quantified rheotaxis of sham-infected and parasite-infected fish in a circular flow tank in the laboratory prior to infection and 5-6 days postinfection. Both parasite-infected and sham-infected individuals expressed similar levels of positive rheotaxis prior to infection and after infection. However, with increasing parasite numbers, guppies covered less distance in the upstream direction and spent more time in slower flow zones. These results suggest that higher numbers of Gyrodactylus ectoparasites negatively influence rheotactic movements. Further research is needed to understand the ecological and evolutionary implications of this ectoparasite on fish movement.

Putative chemical cue from Gyrodactylus-infected guppies subtly alters behaviour but prior exposure decreases parasite intensity.

The reliance on chemical communication is well established for evading predation in aquatic systems. Only a few studies have found evidence that chemical cues released from aquatic animals infected with parasites alter behaviour. Furthermore, the link between putative chemical cues and susceptibility to infection has not been studied. The objectives of this study were to determine if exposure to chemical cues from Gyrodactylus turnbulli-infected guppies (Poecilia reticulata) at various times post-infection resulted in altered behaviour of uninfected conspecifics, and if prior exposure to this putative infection cue reduced transmission. Guppies responded to this chemical cue. Those exposed for 10 min to cues released from fish that had been infected for 8 or 16 days spent less time in the centre half of the tank. Continuous exposure to infection cues for 16 days did not alter guppy shoal behaviour but provided partial protection against infection when the parasite was introduced. Shoals exposed to these putative infection cues became infected, but infection intensity increased more slowly and to a lower peak compared with shoals exposed to the control cue. These results indicate that guppies show subtle behavioural responses to infection cues, and that exposure to infection cues reduces the intensity of outbreaks.

Demonstration gardens improve agricultural production, food security and preschool child diets in subsistence farming communities in Panama.

OBJECTIVES: To explore impacts of a demonstration garden-based agricultural intervention on agricultural knowledge, practices and production, food security and preschool child diet diversity of subsistence farming households. DESIGN: Observational study of households new to the intervention or participating for 1 or 5 years. Variables measured were agricultural techniques learned from the intervention and used, agricultural production, household food insecurity (FIS) and child diet diversity (DDS), over one agricultural cycle (during land preparation, growing and harvest months). SETTING: Fifteen rural subsistence farming communities in Panama. PARTICIPANTS: Households participating in intervention (n 237) with minimum one preschool child. RESULTS: After 1 year, participants had more learned and applied techniques, more staple crops produced and lower FIS and higher DDS during land preparation and growing months compared with those new to the intervention. After 5 years, participants grew more maize, chickens and types of crops and had higher DDS during growing months and, where demonstration gardens persisted, used more learned techniques and children ate more vitamin A-rich foods. Variables associated with DDS varied seasonally: during land preparation, higher DDS was associated with higher household durable asset-based wealth; during growing months, with greater diversity of vegetables planted and lower FIS; during harvest, with older caregivers, caregivers working less in agriculture, more diverse crops and receiving food from demonstration gardens. CONCLUSIONS: The intervention improved food production, food security and diets. Sustained demonstration gardens were important for continued use of new agricultural techniques and improved diets.

Anthropometry before Day 46 and Growth Velocity before 6 Months of Guatemalan Breastfed Infants Are Associated with Subclinical Mastitis and Milk Cytokines, Minerals, and Trace Elements.

BACKGROUND: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland, but its association with human milk composition and infant growth is not well described. OBJECTIVES: We investigated whether SCM, milk cytokines, and/or estimated intakes of milk minerals and trace elements were associated with infant anthropometry or growth velocity before 6 mo. METHODS: Breast milk was collected from Mam-Mayan mothers (n = 114) at both early (2-46 d) and established (4-6 mo) lactation. Concentrations of 9 elements (sodium, potassium, calcium, magnesium, copper, iron, manganese, selenium, zinc) analyzed by inductively-coupled plasma mass spectrometry were used to estimate infants' daily intakes. Concentrations of 4 cytokines were measured. Milk concentrations and infants' estimated elemental intakes and anthropometric measurements during early and established lactation were compared by SCM status. Multiple regression was used to identify factors associated with infant growth attainment (<46 d) for infant weight- (WAZ), length- (LAZ), and head circumference-for-age (HCAZ) and weight-for-length (WLZ) z scores and with growth velocity (expressed as Δ/d) from early to established lactation. RESULTS: SCM prevalence was higher in early (30%) than established (10%) lactation. Breast milk of SCM mothers had higher cytokine concentrations and higher magnesium in early and higher selenium concentrations in both early and established lactation (Padj < 0.0121). At day 46, regression models showed inverse associations of SCM with WLZ and IL-1ß with LAZ (Padj < 0.0150). In contrast, linear growth velocity was positively associated with IL-1ß measured in early lactation (Padj < 0.0124), whereas cranial growth velocity was positively associated with IL-8 measured during established lactation ( Padj < 0.0124). CONCLUSIONS: Despite a high prevalence of inadequate intakes, only infants' intake of milk magnesium during early lactation was associated with linear growth velocity in breastfed infants <6 mo. Evidence shows that SCM, breast-milk cytokines, and infants' estimated intakes of select elements are independently associated with growth attainment and growth velocity during lactation.

Household food insecurity in Panamanian subsistence farming communities is associated with indicators of household wealth and constraints on food production.

OBJECTIVE: To determine if constraints on agricultural production were a novel construct in the Panama Food Security Questionnaire (FSQ) and to characterize agricultural and economic determinants of food insecurity during the planting, growing and harvesting time periods in subsistence farming communities. DESIGN: This longitudinal study followed households during land preparation, growing and harvest periods in one agricultural cycle. Agricultural production and economic variables were recorded and the Panama FSQ was administered. Exploratory factor analysis was used to verify construct validity of the FSQ. A food insecurity score (FIS), ranging from 0 to 42, was derived. Multiple regression analyses of FIS were conducted for each agricultural period. SETTING: Fifteen rural villages in Panama. PARTICIPANTS: Subsistence farming households (n 237). RESULTS: The FSQ contained four constructs: (i) ability to buy food; (ii) decreased amount/number of meals; (iii) feeling hungry; and (iv) lower agricultural production because of weather or lack of resources. Although most households were mildly food insecure in all time periods, determinants of food insecurity differed in each. Higher FIS was associated during land preparation with less rice and legumes planted and lower asset-based wealth; during growing months with less rice, more maize and pigeon peas planted and not selling produce; and during harvest with less rice planted, fewer chickens and lower income. CONCLUSIONS: Constraints on agriculture was a novel construct of the Panama FSQ. Different income-related variables emerged in each agricultural period. Planting staple foods and raising chickens were associated with food security, but some crop choices were associated with food insecurity.

Infant growth faltering linked to subclinical mastitis, maternal faecal-oral contamination, and breastfeeding.

Infant growth faltering occurs in breastfed infants <6 months of age. The possibility that maternal health status contributes to this growth faltering is underexplored. We investigated whether (a) subclinical mastitis (SCM), an asymptomatic inflammation of the breast, (b) maternal intestinal nematode and protozoan infections, indicators of faecal-oral contamination, or (c) poor breastfeeding practices increased the odds of stunting (length-for-age z-score < -2SD), underweight (weight-for-age z-score < -2SD), or low head circumference (head circumference-for-age z-score < -2SD) in breastfed infants in rural indigenous communities in Guatemala. Mother-infant dyads (n = 105) were subdivided into those with and without SCM (milk Na:K ratio > 0.6). Maternal and infant anthropometry were measured at the time of breast milk collection. Maternal stool samples were examined for the presence of intestinal nematodes and protozoa. Questionnaires were used to characterize breastfeeding practices (exclusivity and frequency) and support, hygiene (latrine use and household faucet), and infant diarrhoea. SCM occurred in 14% of women and was associated with increased odds of infant stunting (odds ratio [OR] = 4.3; confidence interval [CI] [1.1, 15.8]), underweight (OR = 9.2; CI [1.8, 48.0]), and low head circumference (OR = 15.9; CI [2.6, 96.9]). Maternal pathogenic protozoa and nematodes were uncommon (<4%), but nonpathogenic protozoa were common (e.g., Entamoeba coli [39%]). Entamoeba coli increased the likelihood (OR = 3.3; CI [1.02, 10.6]) of low head circumference, whereas higher breastfeeding frequency lowered its odds (OR = 0.74, CI [0.56, 0.97]). Prevention of SCM may improve early infant growth, but public health measures that increase breastfeeding frequency and reduce faecal-oral contamination may be required to minimize low head circumference.

Microparasite dispersal in metapopulations: a boon or bane to the host population?

Although connectivity can promote host species persistence in a metapopulation, dispersal may also enable disease transmission, an effect further complicated by the impact that parasite distribution may have on host-parasite population dynamics. We investigated the effects of connectivity and initial parasite distribution (clustered or dispersed) on microparasite-host dynamics in experimental metapopulations, using guppies and Gyrodactylus turnbulli We created metapopulations of guppies divided into four subpopulations and introduced either a low level of parasites to all subpopulations (dispersed) or a high level of parasites to one subpopulation (clustered). Controlled migration among subpopulations occurred every 10 days. In additional trials, we introduced low or high levels of parasites to isolated populations. Parasites persisted longer in metapopulations than in isolated populations. Mortality was lowest in isolated populations with low-level introductions. The interaction of connectivity and initial parasite distribution influenced parasite abundance. With low-level introductions, connectivity helped the parasite persist longer but had little effect on the hosts. With high levels, connectivity also benefited the hosts, lowering parasite burdens. These findings have implications for disease management and species conservation.

Minerals and Trace Elements in Human Breast Milk Are Associated with Guatemalan Infant Anthropometric Outcomes within the First 6 Months.

BACKGROUND: Breast milk is the recommended source of nutrients for infant growth, but its adequacy to meet infants' mineral and trace element needs is unknown. OBJECTIVES: We used breast-milk mineral and trace element concentrations of Guatemalan mothers at 3 lactation stages to estimate total daily intakes and to determine whether intakes were associated with early infant growth. METHODS: In this cross-sectional study, breast-milk samples were collected from Mam-Mayan mothers during transitional (5-17 d, n = 56), early (18-46 d, n = 75), and established (4-6 mo, n = 103) lactation; z scores for weight (WAZ), length (LAZ), and head circumference (HCAZ) were measured. Concentrations of 11 minerals (calcium, potassium, magnesium, sodium, copper, iron, manganese, rubidium, selenium, strontium, and zinc) were analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). WHO equations were used to calculate the estimated energy requirement, which was divided by the energy density of breast milk to estimate daily milk volume, and this number was multiplied by breast-milk mineral concentrations to estimate intakes. Principal component analyses identified clusters of minerals; principal components (PCs) were used in regression analyses for anthropometric outcomes. RESULTS: Estimated breast-milk intakes during established lactation were insufficient to compensate for the lower milk sodium, copper, manganese, and zinc concentrations in male infants and the lower sodium, iron and manganese concentrations in female infants. Estimated intakes of calcium, magnesium, potassium, sodium, and selenium were below the Institute of Medicine Adequate Intake for both sexes at all 3 stages of lactation. In early lactation, multiple linear regressions showed that PC1 (calcium, magnesium, potassium, rubidium, and strontium intakes) was positively associated with WAZ, LAZ, and HCAZ. In established lactation, the same PC with sodium added was positively associated with all 3 anthropometric outcomes; a second PC (PC2: zinc, copper, and selenium intakes) was associated with WAZ and LAZ but not HCAZ. CONCLUSIONS: Breast milk may be inadequate in selected minerals and trace elements where higher estimated intakes were associated with greater infant growth.

Ascaris and hookworm transmission in preschool children in rural Panama: role of subsistence agricultural activities.

This longitudinal study explored whether aspects of subsistence agriculture were associated with presence and intensity of Ascaris and hookworm in preschool children in rural Panama. Questionnaires were used to collect data on household socio-demographics, child exposure to agriculture and household agricultural practices. Stool samples were collected from children (6 months-5 years) at 3 time points, with albendazole administered after each to clear infections, resulting in 1 baseline and 2 reinfection measures. A novel Agricultural Activity Index (AAI) was developed using principal components analysis to measure the intensity of household agricultural practices. Zero-inflated negative binomial regression models revealed baseline hookworm egg counts were higher if children went to the agricultural plot and if the plot was smaller. Baseline and reinfection Ascaris egg counts were higher if children went to the plot and households had higher AAI, and higher at baseline if the plot was smaller. Caregiver time in the plot was negatively associated with baseline Ascaris egg counts, but positively associated with baseline hookworm and Ascaris reinfection egg counts. Children who spent more time playing around the home were less likely to be infected with Ascaris at baseline. We conclude that preschool child exposure to subsistence agriculture increased Ascaris and hookworm intensity.

Protein deficiency and intestinal nematode infection in pregnant mice differentially impact fetal growth through specific stress hormones, growth factors, and cytokines.

BACKGROUND: Protein deficiency (PD) and intestinal nematode infections commonly co-occur during pregnancy and impair fetal growth, but the complex network of signals has not been explored. OBJECTIVE: Our objective was to assess those stress hormones, growth factors, and cytokines affected by maternal PD and nematode infection and associated with fetal growth. METHODS: Using a 2 × 2 factorial design, CD-1 mice, fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets, were either uninfected or infected every 5 d with Heligmosomoides bakeri, beginning on gestational day (GD) 5. Biomarker concentrations were measured on GD 18 in maternal serum (m), fetal serum (f), and amniotic fluid (af) by using Luminex. RESULTS: Maternal PD lowered fetal body mass (PS/uninfected 1.25 ± 0.02 g, PS/infected 1.19 ± 0.02 g vs. PD/uninfected 1.11 ± 0.02 g, PD/infected 0.97 ± 0.02 g; P = 0.02), fetal lung (P = 0.005), and liver (P = 0.003) but not brain mass, whereas maternal infection lowered fetal length (PS/uninfected 2.28 ± 0.02 cm, PD/uninfected 2.27 ± 0.03 cm vs. PS/infected 2.21 ± 0.03 cm, PD/infected 2.11 ± 0.02 cm; P = 0.05) and kidney mass (P = 0.04). PD elevated stress hormones (m-adrenocortiotropic hormone, f-corticosterone, af-corticosterone) and reduced insulin-like growth factor 1 in all compartments (P ≤ 0.01), but these were unassociated with fetal mass or length. Fetal mass was positively associated with f-leptin (R(2) = 0.71, P = 0.0001) and negatively with fetal cytokines [tumor necrosis factor-α: R(2) = 0.62, P = 0.001; interleukin-4 (IL-4): R(2) = 0.63, P = 0.0004]. In contrast, maternal infection lowered f-prolactin (P = 0.02) that was positively associated with fetal length (R(2) = 0.43; P = 0.03); no other biomarker was affected by infection. Regression analyses showed associations between organ growth, cytokines, and growth factors: 1) thymus, spleen, heart, and brain with m-IL-10; 2) brain and kidney with f-vascular endothelial growth factor, af-monocyte chemotactic protein 1, af-interferon-γ, and af-eotaxin; and 3) liver and lung with f-leptin and af-corticosterone (all P ≤ 0.02). CONCLUSIONS: PD and nematode infection impaired fetal mass and linear growth, respectively. Fetal mass, length, and individual organ masses were regulated by different hormones, growth factors, and cytokines.

Ascaris and hookworm transmission in preschool children from rural Panama: role of yard environment, soil eggs/larvae and hygiene and play behaviours.

This study explored whether the yard environment and child hygiene and play behaviours were associated with presence and intensity of Ascaris and hookworm in preschool children and with eggs and larvae in soil. Data were collected using questionnaires, a visual survey of the yard, soil samples and fecal samples collected at baseline and following re-infection. The presence of eggs/larvae in soil was associated negatively with water storage (eggs) but positively with dogs (eggs) and distance from home to latrine (larvae). Baseline and re-infection prevalences were: hookworm (28.0%, 3.4%); Ascaris (16.9%, 9.5%); Trichuris (0.9%, 0.7%). Zero-inflated negative binomial regression models revealed a higher baseline hookworm infection if yards had eggs or larvae, more vegetation or garbage, and if the child played with soil. Baseline Ascaris was associated with dirt floor, dogs, exposed soil in yard, open defecation and with less time playing outdoors, whereas Ascaris re-infection was associated with water storage, vegetation cover and garbage near the home and not playing with animals. Our results show complex interactions between infection, the yard environment and child behaviours, and indicate that transmission would be reduced if latrines were closer to the home, and if open defecation and water spillage were reduced.

Demasculinization of male guppies increases resistance to a common and harmful ectoparasite.

Parasites are detrimental to host fitness and therefore should strongly select for host defence mechanisms. Yet, hosts vary considerably in their observed parasite loads. One notable source of inter-individual variation in parasitism is host sex. Such variation could be caused by the immunomodulatory effects of gonadal steroids. Here we assess the influence of gonadal steroids on the ability of guppies (Poecilia reticulata) to defend themselves against a common and deleterious parasite (Gyrodactylus turnbulli). Adult male guppies underwent 31 days of artificial demasculinization with the androgen receptor-antagonist flutamide, or feminization with a combination of flutamide and the synthetic oestrogen 17 ß-estradiol, and their parasite loads were compared over time to untreated males and females. Both demasculinized and feminized male guppies had lower G. turnbulli loads than the untreated males and females, but this effect appeared to be mainly the result of demasculinization, with feminization having no additional measurable effect. Furthermore, demasculinized males, feminized males and untreated females all suffered lower Gyrodactylus-induced mortality than untreated males. Together, these results suggest that androgens reduce the ability of guppies to control parasite loads, and modulate resistance to and survival from infection. We discuss the relevance of these findings for understanding constraints on the evolution of resistance in guppies and other vertebrates.

Stunting at birth: recognition of early-life linear growth failure in the western highlands of Guatemala.

OBJECTIVE: Measurements of length at birth, or in the neonatal period, are challenging to obtain and often discounted for lack of validity. Hence, classical 'under-5' stunting rates have been derived from surveys on children from 6 to 59 months of age. Guatemala has a high prevalence of stunting (49.8%), but the age of onset of growth failure is not clearly defined. The objective of the study was to assess length-for-age within the first 1.5 months of life among Guatemalan infants. DESIGN: As part of a cross-sectional observational study, supine length was measured in young infants. Mothers' height was measured. Length-for-age Z-scores (HAZ) were generated and stunting was defined as HAZ <-2 using WHO growth standards. SETTING: Eight rural, indigenous Mam-Mayan villages (n 200, 100% of Mayan indigenous origin) and an urban clinic of Quetzaltenango (n 106, 27% of Mayan indigenous origin), Guatemala. SUBJECTS: Three hundred and six newborns with a median age of 19 d. RESULTS: The median rural HAZ was -1.56 and prevalence of stunting was 38%; the respective urban values were -1.41 and 25%. Linear regression revealed no relationship between infant age and HAZ (r = 0.101, r(2) = 0.010, P = 0.077). Maternal height explained 3% of the variability in HAZ (r = 0.171, r(2) = 0.029, P = 0.003). CONCLUSIONS: Stunting must be carried over from in utero growth retardation in short-stature Guatemalan mothers. As linear growth failure in this setting begins in utero, its prevention must be linked to maternal care strategies during gestation, or even before. A focus on maternal nutrition and health in an intergenerational dimension is needed to reduce its prevalence.

Quantitative Methodologies Reveal a Diversity of Nutrition, Infection/Illness, and Psychosocial Stressors During Pregnancy and Lactation in Rural Mam-Mayan Mother-Infant Dyads From the Western Highlands of Guatemala.

BACKGROUND: The nature and severity of 3 categories of maternal stressors (nutritional, infectious, and psychosocial) that may impact maternal health and early infant growth are not often considered together. OBJECTIVES: To describe quantitative methodologies; assess construct validity of questionnaires; report variability in sociodemographic, obstetric, nutritional, infectious, and psychosocial characteristics; and compare characteristics between pregnancy and lactation and between study cohorts of Mam-Mayan mother-infant dyads. METHODS: Grounded in participatory action research and a socioecological framework, this observational study enrolled a longitudinal cohort of 155 women, followed during pregnancy (6-9 months), early (0-6 weeks), and later (4-6 months) postpartum, and 2 cross-sectional cohorts (60 early and 56 later postpartum). Household and social factors; obstetric history; nutritional, infectious, and psychosocial stressors; and infant characteristics were explored. RESULTS: Diet diversity (3.4 ± 1.3) and adult food security (38%) were low. Urinary and gastrointestinal infections were rare (<5%), whereas experience of local idioms of distress was frequent (20%-50%). Participants reported low maternal autonomy (81%), high paternal support (70%), small social support networks (2.7 ± 1.3 individuals), and high trust in family (88%) and community-based institutions (61%-65%) but low trust in government services (6%). Domestic violence was commonly reported (22%). Infant stunting was common (36% early postpartum and 43% later postpartum) despite frequent antenatal care visits (7.5 ± 3.8). Participant engagement with the research team did not influence study outcomes based on comparisons between longitudinal and cross-sectional cohorts. CONCLUSIONS: The variability in sociodemographic, nutritional, and psychosocial variables, will allow exploration of factors that promote resilience or increase vulnerability of the mother-infant dyad.

Protein deficiency alters impact of intestinal nematode infection on intestinal, visceral and lymphoid organ histopathology in lactating mice.

Protein deficiency impairs local and systemic immune responses to Heligmosomoides bakeri infection but little is known about their individual and interactive impacts on tissue architecture of maternal lymphoid (thymus, spleen) and visceral (small intestine, kidney, liver, pancreas) organs during the demanding period of lactation. Using a 2 × 2 factorial design, pregnant CD1 mice were fed a 24% protein sufficient (PS) or a 6% protein deficient (PD) isoenergetic diet beginning on day 14 of pregnancy and were infected with 100 H. bakeri larvae four times or exposed to four sham infections. On day 20 of lactation, maternal organs were examined histologically and serum analytes were assayed as indicators of organ function. The absence of villus atrophy in response to infection was associated with increased crypt depth and infiltration of mast cells and eosinophils but only in lactating dams fed adequate protein. Infection-induced lobular liver inflammation was reduced in PD dams, however, abnormalities in the kidney caused by protein deficiency were absent in infected dams. Bilirubin and creatinine were highest in PD infected mice. Infection-induced splenomegaly was not due to an increase in the lymphoid compartment of the spleen. During lactation, infection and protein deficiency have interactive effects on extra-intestinal pathologies.

Maternal gastrointestinal nematode infection alters hippocampal neuroimmunity, promotes synaptic plasticity, and improves resistance to direct infection in offspring.

The developing brain is vulnerable to maternal bacterial and viral infections which induce strong inflammatory responses in the mother that are mimicked in the offspring brain, resulting in irreversible neurodevelopmental defects, and associated cognitive and behavioural impairments. In contrast, infection during pregnancy and lactation with the immunoregulatory murine intestinal nematode, Heligmosomoides bakeri, upregulates expression of genes associated with long-term potentiation (LTP) of synaptic networks in the brain of neonatal uninfected offspring, and enhances spatial memory in uninfected juvenile offspring. As the hippocampus is involved in spatial navigation and sensitive to immune events during development, here we assessed hippocampal gene expression, LTP, and neuroimmunity in 3-week-old uninfected offspring born to H. bakeri infected mothers. Further, as maternal immunity shapes the developing immune system, we assessed the impact of maternal H. bakeri infection on the ability of offspring to resist direct infection. In response to maternal infection, we found an enhanced propensity to induce LTP at Schaffer collateral synapses, consistent with RNA-seq data indicating accelerated development of glutamatergic synapses in uninfected offspring, relative to those from uninfected mothers. Hippocampal RNA-seq analysis of offspring of infected mothers revealed increased expression of genes associated with neurogenesis, gliogenesis, and myelination. Furthermore, maternal infection improved resistance to direct infection of H. bakeri in offspring, correlated with transfer of parasite-specific IgG1 to their serum. Hippocampal immunohistochemistry and gene expression suggest Th2/Treg biased neuroimmunity in offspring, recapitulating peripheral immunoregulation of H. bakeri infected mothers. These findings indicate maternal H. bakeri infection during pregnancy and lactation alters peripheral and neural immunity in uninfected offspring, in a manner that accelerates neural maturation to promote hippocampal LTP, and upregulates the expression of genes associated with neurogenesis, gliogenesis, and myelination.

Multiple Infections, Nutrient Deficiencies, and Inflammation as Determinants of Anemia and Iron Status during Pregnancy: The MINDI Cohort.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Experimental elimination of parasites in nature leads to the evolution of increased resistance in hosts.

A reduction in the strength of selection is expected to cause the evolution of reduced trait expression. Elimination of a parasite should thus cause the evolution of reduced resistance to that parasite. To test this prediction in nature, we studied the fourth- and eighth-generation descendants of guppies (Poecilia reticulata) introduced into four natural streams following experimental elimination of a common and deleterious parasite (Gyrodactylus spp.). After two generations of laboratory rearing to control for plasticity and maternal effects, we infected individual fish to assess their resistance to the parasite. Contrary to theoretical expectations, the introduced guppy populations had rapidly and repeatably evolved increased resistance to the now-absent parasite. This evolution was not owing to a resistance-tolerance trade-off, nor to differences in productivity among the sites. Instead, a leading candidate hypothesis is that the rapid life-history evolution typical in such introductions pleiotropically increases parasite resistance. Our study adds a new dimension to the growing evidence for contemporary evolution in the wild, and also points to the need for a re-consideration of simple expectations from host-parasite theory. In particular, our results highlight the need for increased consideration of multiple sources of selection and pleiotropy when studying evolution in natural contexts.

Maternal protein deficiency during a gastrointestinal nematode infection alters developmental profile of lymphocyte populations and selected cytokines in neonatal mice.

Neonatal immune development begins in pregnancy and continues into lactation and may be affected by maternal diet. We investigated the possibility that maternal protein deficiency (PD) during a chronic gastrointestinal (GI) nematode infection could impair neonatal immune development. Beginning on d 14 of pregnancy, mice were fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets and were infected weekly with either 0 (sham) or 100 Heligmosomoides bakeri larvae. Pups were killed on d 2, 7, 14, and d 21 and dams on d 20 of lactation. Lymphoid organs were weighed. Cytokine concentration in maternal and pup serum and in milk from pup stomachs and lymphoid cell populations in pup spleen and thymus were determined using luminex and flow cytometry, respectively. GI nematode infection increased Th2 cytokines (IL-4, IL-5, IL-13), IL-2, IL-10, and eotaxin in serum of dams whereas PD reduced IL-4 and IL-13. The lower IL-13 in PD dams was associated with increased fecal egg output and worm burdens. Maternal PD increased vascular endothelial growth factor in pup milk and eotaxin in pup serum. Maternal infection increased eotaxin in pup serum. Evidence of impaired neonatal immune development included reduced lymphoid organ mass in pups associated with both maternal infection and PD and increased percentage of T cells and T:B cell ratio in the spleen associated with maternal PD. Findings suggest that increases in specific proinflammatory cytokines as a result of the combination of infection and dietary PD in dams can impair splenic immune development in offspring.