Biomedical subjects

Elizabeth T Abrams

Publications and source records attributed to Elizabeth T Abrams.

7 recordsLinked to original sources

PubMed2005

Malaria during pregnancy and foetal haematological status in Blantyre, Malawi.

BACKGROUND: Although maternal anaemia often stems from malaria infection during pregnancy, its effects on foetal haemoglobin levels are not straightforward. Lower-than-expected cord haemoglobin values in malarious versus non-malarious regions were noted by one review, which hypothesized they resulted from foetal immune activation to maternal malaria. This study addressed this idea by examining cord haemoglobin levels in relation to maternal malaria, anaemia, and markers of foetal immune activation. METHODS: Cord haemoglobin levels were examined in 32 malaria-infected and 58 uninfected women in Blantyre, Malawi, in relation to maternal haemoglobin levels, malaria status, and markers of foetal haematological status, hypoxia, and inflammation, including TNF-alpha, TGF-beta, and ferritin. All women were HIV-negative. RESULTS: Although malaria was associated with a reduction in maternal haemoglobin (10.8 g/dL vs. 12.1 g/dL, p < 0.001), no reduction in cord haemoglobin and no significant relationship between maternal and cord haemoglobin levels were found. Cord blood markers of haematological and hypoxic statuses did not differ between malaria-infected and uninfected women. Maternal malaria was associated with decreased TGF-beta and increased cord ferritin, the latter of which was positively correlated with parasitaemia (r = 0.474, p = 0.009). Increased cord ferritin was associated with significantly decreased birth weight and gestational length, although maternal and cord haemoglobin levels and malaria status had no effect on birth outcome. CONCLUSION: In this population, cord haemoglobin levels were protected from the effect of maternal malaria. However, decreased TGF-beta and elevated ferritin levels in cord blood suggest foetal immune activation to maternal malaria, which may help explain poor birth outcomes.

Adolescent↗

PubMed2004

The effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA concentrations in pregnant Malawian women.

OBJECTIVE: To investigate the effect of placental Plasmodium falciparum malaria infection on peripheral and/or placental HIV-1 viral load. DESIGN: A cross-sectional study of HIV-infected pregnant women, with and without placental malaria, delivering at Queen Elizabeth Central Hospital in Malawi. METHODS: Peripheral blood samples were collected from consenting women and tested for HIV. HIV-infected women received nevirapine at the onset of labor. At delivery, placental blood and tissue specimens were collected. HIV-1 RNA concentrations were measured in peripheral and placental plasma samples, and malaria infection was determined by placental histopathology. RESULTS: Of the 480 HIV-infected women enrolled, 304 had placental histopathology performed, of whom 74 (24.3%) had placental malaria. Compared with women without placental malaria, those with placental malaria had a 2.5-fold higher geometric mean peripheral HIV-1 RNA concentration (62,359 versus 24 814 copies/ml; P = 0.0007) and a 2.4-fold higher geometric mean placental HIV-1 RNA concentration (11,733 versus 4919 copies/ml; P = 0.008). In multivariate analyses, after adjusting for CD4 cell count and other covariates, placental malaria was associated with a 1.7-fold increase in geometric mean peripheral HIV-1 RNA concentration (47,747 versus 27,317 copies/ml; P = 0.02) and a 2.0-fold increase in geometric mean placental HIV-1 RNA concentration (9670 versus 4874 copies/ml; P = 0.03). CONCLUSION: Placental malaria infection is associated with an increase in peripheral and placental HIV-1 viral load, which might increase the risk of mother-to-child transmission of HIV.

Adult↗

PubMed2004

Infant mouthing behavior: the immunocalibration hypothesis.

Avid mouthing, the propensity of infants to suck objects and put them in their mouths, is a pattern characteristic of the first 2-3 years of life, with its most intensive manifestation occurring during the first year. Although traditional accounts explain infant mouthing as a source of sensual gratification and/or environmental exploration, these proximate hypotheses are inconsistent with the high costs of mouthing, including choking, poisoning, and exposure to pathogens. We propose that mouthing serves to proactively expose the naive gastrointestinal tract to environmental antigens and commensal bacteria while under the sheltering umbrella of breastfeeding. Mouthing functions to accurately calibrate the developing immune system, including antibody production and mucosal immunity, to the local disease ecology. The critical exposure period is not open-ended, as failure to expose the gut to an adequate number of antigens early in life is associated with an increased risk of allergies, asthma, and atopy. Weaning initiates a number of immune changes that may program the neonatal immune system into certain life-long responses.

Child, Preschool↗

PubMed2004

Risk factors and mechanisms of preterm delivery in Malawi.

PROBLEM: We examined risk factors and mechanisms of preterm delivery (PTD) in malaria-exposed pregnant women in Blantyre, Malawi. METHOD OF STUDY: The human immunodeficiency virus (HIV), malaria, syphilis, and anemia were assessed in a cross-sectional study of 572 pregnant women. In a nested case-control study, chorioamnionitis (CAM) was examined; tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-beta, cortisol, and corticotropin-releasing hormone were measured in placental, maternal and/or cord blood. RESULTS: HIV, infrequent antenatal clinic attendance, low-maternal weight, no intermittent preventive malaria therapy (IPT), and CAM were associated with PTD, while malaria was not. Of the 18 compartmental cytokine measurements, elevations in placental and/or cord IL-6 and IL-8 were associated with both CAM and PTD. In contrast, there was no overlap between the cytokines affected by malaria and those associated with PTD. CONCLUSIONS: The HIV and CAM were the major infections associated with PTD in this study. CAM, but not malaria, causes PTD via its effect on proinflammatory cytokines.

Anemia↗

PubMed2004

Whole-body leucine kinetics and the acute phase response during acute infection in marasmic Malawian children.

This study compared leucine kinetics and acute-phase protein and cytokine concentrations in three groups of Malawian children who were fed an isoenergetic, isonitrogenous diet: children with marasmus with (n = 25) and without (n = 17) infection and well-nourished children with infection (n =13). The hypotheses tested were that whole-body leucine kinetics will be less in marasmic acutely infected children than in well-nourished acutely infected children but greater than in marasmic uninfected children. Children were studied after 24 h of therapy using standard (13)C-leucine stable isotope tracer techniques. Well-nourished children with acute infection had greater leucine kinetic rates than did marasmic children with acute infection; nonoxidative leucine disposal was 153 +/- 31 versus 118 +/- 43 micromol leucine. kg(-1). h(-1), leucine derived from whole-body proteolysis was 196 +/- 34 versus 121 +/- 47, and leucine oxidation was 85 +/- 31 versus 45 +/- 13 (p < 0.01 for all comparisons). Leucine kinetic rates were similar in marasmic children with and without acute infection. Well-nourished children with acute infection increased their serum concentration of five of six acute-phase proteins during the first 24 h, whereas marasmic children with infection did not have any increases. The serum concentrations of IL-6 were elevated in well-nourished and marasmic children with infection. These data suggest that the cytokine stimulus for the acute-phase protein kinetic response to acute infection is present in marasmic children but that the acute-phase protein metabolic response is blunted by malnutrition.

Acute Disease↗

PubMed2003

Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression.

Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.

Birth Weight↗

PubMed2003

Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women.

Malaria in pregnancy predisposes to maternal anemia and low birth weight (LBW). We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in these adverse outcomes. We measured cytokine concentrations in placental, peripheral, and cord blood plasma in relation to malaria parasitemia and placental monocyte accumulation in 276 Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus status, and infant birth weight were determined. Concentrations of TNF-alpha in placental blood were correlated with densities of Plasmodium falciparum-infected erythrocytes (P < 0.0001) and of intervillous monocyte infiltrates (P < 0.0001) on placental histology. Peripheral blood TNF-alpha concentrations were relatively low and were weakly associated with malaria. TNF-alpha concentrations were higher in placental blood, where they were strongly associated with malaria. Placental plasma TNF-alpha levels were higher in women who had LBW babies (P = 0.0027), women with febrile symptoms (P < 0.0001), and teenage mothers (P = 0.04) than in other women. The presence of TNF-alpha in cord blood was not associated with malaria infection. IFN-gamma levels were infrequently elevated, and elevated IFN-gamma levels were not associated with poor pregnancy outcomes. Placental production of TNF-alpha, but not of IFN-gamma, may be implicated in impaired fetal growth in Malawian women.

AIDS-Related Opportunistic Infections↗