Immune Activation and Microbial Translocation Markers in HIV-Exposed Uninfected Malawian Infants in the First Year of Life

2019 ◽  
Vol 65 (6) ◽  
pp. 617-625 ◽  
Author(s):  
Silvia Baroncelli ◽  
Clementina Maria Galluzzo ◽  
Giuseppe Liotta ◽  
Mauro Andreotti ◽  
Sandro Mancinelli ◽  
...  
Keyword(s):  
Immune Activation ◽  
Binding Protein ◽  
Microbial Translocation ◽  
First Year ◽  
Gastrointestinal Infections ◽  
Fatty Acid Binding ◽  
Hiv Exposed ◽  
First Year Of Life ◽  
The Impact ◽  
Exposed Uninfected

Abstract Background HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life. Methods Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally. Results Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 μg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018). Conclusion We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings.

Immunologic and Virologic Factors Associated with Hospitalization in HIV-Exposed, Uninfected Infants in the United States

2021 ◽  
Author(s):  
Christiana Smith ◽  
Yanling Huo ◽  
Kunjal Patel ◽  
Kirk Fetters ◽  
Shannon Hegemann ◽  
...  
Keyword(s):  
United States ◽  
Regression Models ◽  
The United States ◽  
Pediatric Hiv ◽  
First Year ◽  
Virus Family ◽  
Vaccine Antigens ◽  
Hiv Exposed ◽  
First Year Of Life ◽  
Exposed Uninfected

Abstract Background HIV-exposed, uninfected (HEU) infants experience higher rates of morbidity and mortality than HIV-unexposed uninfected (HUU) infants. Few studies have examined whether particular infections and/or immune responses are associated with hospitalization among HEU infants born in the United States. Methods We evaluated a subset of HEU infants enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1025 and/or Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for ART Toxicities studies. We determined seroconversion to 6 respiratory viruses and measured antibody concentrations to 9 vaccine antigens using quantitative ELISA or electrochemiluminesence. Multivariable modified Poisson regression models were fit to evaluate the associations of seroconversion to each respiratory virus/family and antibody concentrations to vaccine antigens with the risk of hospitalization in the first year of life. Antibody concentrations to vaccine antigens were compared between HEU infants and HUU infants from a single site using multivariable linear regression models. Results Among 556 HEU infants, seroconversion to respiratory syncytial virus (RSV) and parainfluenza were associated with hospitalization [adjusted risk ratio: 1.95 (95% CI 1.21-3.15); 2.30 (1.42-3.73), respectively]. Antibody concentrations to tetanus toxoid, pertussis, and pneumococcal vaccine antigens were higher among 525 HEU compared with 100 HUU infants. No associations were observed between antibody concentrations to any vaccine and hospitalization among HEU infants. Conclusions RSV and parainfluenza contribute to hospitalization among HEU infants in the first year of life. HEU infants demonstrate robust antibody responses to vaccine antigens; therefore, humoral immune defects likely do not explain the increased susceptibility to infection observed in this population.

scholarly journals 376. Effect of Parasitic Infections on Gut Epithelial Barrier and Immune Activation among Foreign-Born HIV-infected Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S196-S197
Author(s):  
Melissa Reimer-McAtee ◽  
Anoma Somasunderam ◽  
Teena Huan Xu ◽  
Roberto Arduino ◽  
Jose Serpa ◽  
...  
Keyword(s):  
Immune Activation ◽  
Strongyloides Stercoralis ◽  
The United States ◽  
Microbial Translocation ◽  
Cd4 Count ◽  
Parasitic Infections ◽  
Foreign Born ◽  
Hiv Diagnosis ◽  
Fatty Acid Binding ◽  
The Impact

Abstract Background Strongyloides stercoralis often causes an asymptomatic infection despite continuous autoinfection for the lifetime of the host. Both HIV and recurrent enteric parasitic infections cause gut damage and increased microbial translocation, but little is known about the effects of co-infection. We aimed to evaluate changes in immune activation, mucosal damage, and microbial translocation in people with HIV-1 (PWH) and parasite co-infection. Methods In this pilot prospective cohort study, we enrolled foreign-born PWH on suppressive antiretroviral therapy (ART) in an ambulatory clinic in Houston, Texas. We evaluated serum Strongyloides IgG using ELISA with an S. stercoralis-specific recombinant protein. Intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), sCD163, IL-6, and sTNFRII were analyzed as markers of enterocyte turnover, inflammation, and immune activation. Non-parametric tests were used for analysis. Results 52 participants born in 14 countries were enrolled February–March 2019. Median CD4 count was 464/uL [95% CI 315–598]. Fourteen (27%) were positive for Strongyloides IgG. Strongyloides IgG levels correlated positively with sCD14 levels [r=0.36; P = 0.008]. Strongyloides+ participants had significantly higher sCD14 levels compared with Strongyloides− participants [1.67 vs. 1.48 μg/mL, P = 0.031]. Among the Strongyloides+ participants, Strongyloides IgG levels correlated with sCD163 levels [r=0.65, P = 0.026]. There were no difference in the other biomarkers. Logistical regression analysis showed that predictors of Strongyloides+ include absolute eosinophil count (AEC) (OR 1.45 for every 100 increase of AEC [95% CI: 1.02, 2.15; P = 0.047]). CD4 count, number of years living in the United States, country of origin, and years from HIV diagnosis were not associated with test positivity. Conclusion Strongyloides co-infection is common among foreign-born PWH and may contribute to chronic monocyte/macrophage activation, a predictor of morbidity and mortality in PWH. Future directions include stool PCR confirmation of these infections, continued enrollment, and follow-up assays 6 months after treatment of Strongyloides to determine the impact on inflammation and risk of co-morbidities. Disclosures All authors: No reported disclosures.

scholarly journals Quality of Caregiving is Positively Associated With Neurodevelopment During the First Year of Life Among HIV-Exposed Uninfected Children in Uganda

2018 ◽  
Vol 77 (3) ◽  
pp. 235-242 ◽  
Author(s):  
Itziar Familiar ◽  
Shalean M. Collins ◽  
Alla Sikorskii ◽  
Horacio Ruisenor-Escudero ◽  
Barnabas Natamba ◽  
...  
Keyword(s):  
First Year ◽  
Hiv Exposed ◽  
First Year Of Life ◽  
Exposed Uninfected

scholarly journals 284. Antibiotic Usage in the First Year of Life in HIV-Exposed, Uninfected Infants in Malawi: Results From the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S117-S117
Author(s):  
Athena Kourtis ◽  
Alexander Ewing ◽  
Nicole Davis ◽  
Dumbani Kayira ◽  
Mina Hosseinipour ◽  
...  
Keyword(s):  
Antibiotic Usage ◽  
First Year ◽  
Hiv Exposed ◽  
First Year Of Life ◽  
Exposed Uninfected

scholarly journals HIV-Exposed Uninfected Infants are at Increased Risk for Severe Infections in the First Year of Life

2012 ◽  
Vol 58 (6) ◽  
pp. 505-508 ◽  
Author(s):  
A. Slogrove ◽  
B. Reikie ◽  
S. Naidoo ◽  
C. De Beer ◽  
K. Ho ◽  
...  
Keyword(s):  
First Year ◽  
Increased Risk ◽  
Severe Infections ◽  
Hiv Exposed ◽  
First Year Of Life ◽  
Exposed Uninfected

scholarly journals Breastfeeding, maternal asthma and wheezing in the first year of life: a longitudinal birth cohort study

2017 ◽  
Vol 49 (5) ◽  
pp. 1602019 ◽  
Author(s):  
Meghan B. Azad ◽  
Lorena Vehling ◽  
Zihang Lu ◽  
David Dai ◽  
Padmaja Subbarao ◽  
...  
Keyword(s):  
Birth Cohort ◽  
Respiratory Health ◽  
Birth Cohort Study ◽  
P Value ◽  
First Year ◽  
Dependent Manner ◽  
Complementary Foods ◽  
Adjusted Rate ◽  
First Year Of Life ◽  
The Impact

The impact of breastfeeding on respiratory health is uncertain, particularly when the mother has asthma. We examined the association of breastfeeding and wheezing in the first year of life.We studied 2773 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Caregivers reported on infant feeding and wheezing episodes at 3, 6 and 12 months. Breastfeeding was classified as exclusive, partial (supplemented with formula or complementary foods) or none.Overall, 21% of mothers had asthma, 46% breastfed for at least 12 months and 21% of infants experienced wheezing. Among mothers with asthma, breastfeeding was inversely associated with infant wheezing, independent of maternal smoking, education and other risk factors (adjusted rate ratio (aRR) 0.52; 95% CI 0.35–0.77 for ≥12 versus <6 months breastfeeding). Compared with no breastfeeding at 6 months, wheezing was reduced by 62% with exclusive breastfeeding (aRR 0.38; 95% CI 0.20–0.71) and by 37% with partial breastfeeding supplemented with complementary foods (aRR 0.63; 95% CI 0.43–0.93); however, breastfeeding was not significantly protective when supplemented with formula (aRR 0.89; 95% CI 0.61–1.30). Associations were not significant in the absence of maternal asthma (p-value for interaction <0.01).Breastfeeding appears to confer protection against wheezing in a dose-dependent manner among infants born to mothers with asthma.

scholarly journals The development of the cortisol response to dyadic stressors in Black and White infants

2018 ◽  
Vol 30 (5) ◽  
pp. 1995-2008 ◽  
Author(s):  
Andrew Dismukes ◽  
Elizabeth Shirtcliff ◽  
Christopher W. Jones ◽  
Charles Zeanah ◽  
Katherine Theall ◽  
...  
Keyword(s):  
Urban Life ◽  
First Year ◽  
Strange Situation ◽  
Cortisol Reactivity ◽  
Hypothalamic Pituitary Adrenal ◽  
Black And White ◽  
First Year Of Life ◽  
The Impact ◽  
Still Face Paradigm ◽  
Strange Situation Procedure

AbstractAcute reactivity of the stress hormone cortisol is reflective of early adversity and stress exposure, with some studies finding that the impact of adversity on the stress response differs by race. The objectives of the current study were to characterize cortisol reactivity to two dyadically based stress paradigms across the first year of life, to examine cortisol reactivity within Black and White infants, and to assess the impact of correlates of racial inequity including socioeconomic status, experiences of discrimination, and urban life stressors, as well as the buffering by racial socialization on cortisol patterns. Salivary cortisol reactivity was assessed at 4 months of age during the Still Face paradigm (N = 207) and at 12 months of age across the Strange Situation procedure (N = 129). Infants demonstrated the steepest recovery after the Still Face paradigm and steepest reactivity to the Strange Situation procedure. Race differences in cortisol were not present at 4 months but emerged at 12 months of age, with Black infants having higher cortisol. Experiences of discrimination contributed to cortisol differences within Black infants, suggesting that racial discrimination is already “under the skin” by 1 year of age. These findings suggest that race-related differences in hypothalamic–pituitary–adrenal reactivity are present in infancy, and that the first year of life is a crucial time period during which interventions and prevention efforts for maternal–infant dyads are most likely able to shape hypothalamic–pituitary–adrenal reactivity thereby mitigating health disparities early across the life course.

Impact of intrapartum antibiotics on the infant gastrointestinal microbiome: a narrative review

2021 ◽  
pp. archdischild-2021-322590
Author(s):  
Laura Diamond ◽  
Rachel Wine ◽  
Shaun K Morris
Keyword(s):  
Gestational Age ◽  
Beta Diversity ◽  
Mode Of Delivery ◽  
Alpha Diversity ◽  
First Year ◽  
Feeding Method ◽  
Alpha And Beta Diversity ◽  
Ovid Medline ◽  
First Year Of Life ◽  
The Impact

BackgroundThe composition of the infant gastrointestinal (GI) microbiome has been linked to adverse long-term health outcomes and neonatal sepsis. Several factors are known to impact the composition of the microbiome, including mode of delivery, gestational age, feeding method and exposure to antibiotics. The impact of intrapartum antibiotics (IPAs) on the infant microbiome requires further research.ObjectiveWe aimed to evaluate the impact of IPAs on the infant GI microbiome.MethodsWe searched Ovid MEDLINE and Embase Classic+Embase for articles in English reporting on the microbiome of infants exposed to IPAs from the date of inception to 3 January 2021. Primary outcomes included abundance and colonisation of Bifidobacterium and Lactobacillus, as well as alpha and beta diversity.Results30 papers were included in this review. In the first year of life, following exposure to IPAs, 30% (6/20) of infant cohorts displayed significantly reduced Bifidobacterium, 89% (17/19) did not display any significant differences in Lactobacillus colonisation, 21% (7/34) displayed significantly reduced alpha diversity and 35% (12/34) displayed alterations in beta diversity. Results were further stratified by delivery, gestational age (preterm or full term) and feeding method.ConclusionsIPAs impact the composition of the infant GI microbiome, resulting in possible reductions Bifidobacterium and alpha diversity, and possible alterations in beta diversity. Our findings may have implications for maternal and neonatal health, including interventions to prevent reductions in health-promoting bacteria (eg, probiotics) and IPA class selection.

scholarly journals Rosuvastatin Decreases Intestinal Fatty Acid Binding Protein (I-FABP), but does not Alter Zonulin or Lipopolysaccharide Binding Protein (LBP) Levels, in HIV-Infected Subjects on Antiretroviral Therapy

2016 ◽  
Vol 1 (1) ◽  
pp. 118 ◽  
Author(s):  
Nicholas Funderburg ◽  
Morgan Boucher ◽  
Abdus Sattar ◽  
Manjusha Kulkarni ◽  
Danielle Labbato ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Immune Activation ◽  
Inflammatory Markers ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Lipopolysaccharide Binding Protein ◽  
Fatty Acid Binding ◽  
Barrier Integrity ◽  
Acid Binding Protein ◽  
Lipopolysaccharide Binding

Introduction: Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection. We have reported that rosuvastatin improved several markers of immune activation in HIV+ participants, but the effect of statin treatment on markers of GI barrier dysfunction is unknown.Methods: SATURN-HIV is a randomized, double-blind, placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on markers of cardiovascular disease, inflammation, and immune activation in ART-treated patients. Gut-barrier integrity was assessed by the surrogate markers intestinal fatty acid binding protein (I-FABP), a marker of enterocyte death, and zonulin-1, a marker of gut epithelial cell function. Levels of lipopolysaccharide binding protein (LBP) were measured as a marker of microbial translocation.Results: Rosuvastatin significantly reduced levels of I-FABP during the treatment period compared to the placebo. There was no effect of rosuvastatin treatment on levels of zonulin or LBP. Baseline levels of LBP were directly related to several markers of immune activation in samples from all participants, including soluble CD163, IP-10, VCAM-1, TNFR-II, and the proportion of CD4+ and CD8+ T cells expressing CD38 and HLA-DR. Many of these relationships, however, were not seen in the statin arm alone at baseline or over time, as inflammatory markers often decreased and LBP levels were unchanged.Conclusions: Forty-eight weeks of rosuvastatin treatment reduced levels of I-FABP, but did not affect levels of zonulin or LBP. The reduction in levels of inflammatory markers that we have reported with rosuvastatin treatment is likely mediated through other mechanisms not related to gut integrity or microbial translocation.SATURN-HIV is registered on clinicaltrials.gov; Identifier: NCT01218802

scholarly journals Persistent Systemic Microbial Translocation, Inflammation, and Intestinal Damage During Clostridioides difficile Infection

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Alessandra Oliva ◽  
Lucia Aversano ◽  
Massimiliano De Angelis ◽  
Maria Teresa Mascellino ◽  
Maria Claudia Miele ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Cell Damage ◽  
Binding Protein ◽  
Fecal Microbiota ◽  
Microbial Translocation ◽  
Intestinal Cell ◽  
Intestinal Damage ◽  
Fatty Acid Binding ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection

Abstract Background Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI. Methods Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively. Results Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P &lt; .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values. Conclusions CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.

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