Current Opinion in Infectious Diseases
June 2016 – Volume 29 – Issue 3 pp: v-v,229-318
http://journals.lww.com/co-infectiousdiseases/pages/currenttoc.aspx
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PAEDIATRIC AND NEONATAL INFECTIONS
Edited by Paul T. Heath

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Interactions between intestinal pathogens, enteropathy and malnutrition in developing countries
Prendergast, Andrew J.; Kelly, Paul
Abstract
Purpose of review: This review focuses on recent data highlighting the interactions between intestinal pathogens, enteropathy and malnutrition in developing countries, which drive morbidity and mortality and hinder the long-term developmental potential of children.
Recent findings: Diarrhoea remains the second commonest cause of death in children below 5 years, and malnutrition underlies 45% of all child deaths. Even in the absence of diarrhoea, subclinical pathogen carriage and enteropathy are almost universal in developing countries. Here, we review recent studies addressing the causes and consequences of diarrhoea; emerging data on environmental influences that govern postnatal development of the gut and microbiota; current concepts of environmental enteric dysfunction; and recent intervention trials in the field. We highlight the interactions between these processes, whereby intestinal pathogens drive a cycle of gut damage, malabsorption, chronic inflammation and failed mucosal regeneration, leading to malnutrition and susceptibility to further enteric infections.
Summary: Efforts to improve child survival and long-term developmental potential need to address the overlapping and interacting effects of diarrhoea, enteropathy and malnutrition. Recent insights from human and animal studies suggest potential targets for intervention.
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HIV-1 at the placenta: immune correlates of protection and infection
Johnson, Erica L.; Chakraborty, Rana
Abstract
Purpose of review: Mother-to-child transmission (MTCT) of HIV-1 remains a significant global health concern despite implementation of maternal combination antiretroviral therapy for treatment as prevention to offset transmission. The risk of in-utero HIV-1 transmission in the absence of interventions is ∼7%. This low rate of transmission points to innate and adaptive mechanisms to restrict lentiviral infection within the placenta.
Recent findings: Placental macrophages (Hofbauer cells) are key mediators in in-utero transmission of HIV-1. Hofbauer cells constitutively express elevated concentrations of regulatory cytokines, which inhibit HIV-1 replication in vitro, and possess intrinsic antiviral properties. Hofbauer cells sequester HIV-1 in intracellular compartments that can be accessed by HIV-1-specific antibodies and may occur in vivo to offset MTCT. Intriguingly, studies have reported strong associations between maternal human cytomegalovirus (HCMV) viremia and MTCT of HIV-1. HCMV infection at the placenta promotes inflammation, chronic villitis, and trophoblast damage, providing potential HIV-1 access into CD4+CCR5+ target cells. The placenta exhibits a variety of mechanisms to limit HIV-1 replication, yet viral-induced activation with maternal HCMV may override this protection to facilitate in-utero transmission of HIV-1.
Summary: Understanding immune correlates of protection or transmission at the placenta during on-going HIV-1 exposure may contribute to understanding HIV pathogenesis and the development of effective immunotherapies.
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Group B Streptococcus: developing a correlate of protection for a vaccine against neonatal infections
Dangor, Ziyaad; Lala, Sanjay G.; Kwatra, Gaurav; More
Abstract
Purpose of review: Maternal vaccination to prevent invasive Group B Streptococcus (GBS) disease in infants is an important alternative strategy to intrapartum antibiotic prophylaxis. Licensure of GBS vaccines could be expedited using immunological correlates of protection.
Recent findings: Between 2014 and 2015, we identified two studies that demonstrated an inverse association between invasive GBS disease and maternal serotype III capsular antibody levels greater than 1 μg/ml and greater than 3 μg/ml, and higher maternal antibody levels were associated with protection against serotype Ia disease. Furthermore, serotype Ia and III antibody levels greater than 3 μg/ml were associated with a reduced risk of GBS colonization in pregnant women.
Experimental studies have investigated the use of GBS surface proteins as vaccine candidates. Although the immunogenic potential of pilus island and other surface proteins has been shown in animal-model studies, no association between maternal pilus island antibody levels and invasive GBS disease was demonstrated in infants. Additionally, several novel innate immune mediators that prevent GBS infection have been described in human and experimental studies.
Summary: Recent studies suggest that maternal capsular antibody thresholds may be used as immunological correlates of protection for vaccine licensure. Surface proteins, as candidate vaccines or conjugates to the polysaccharide-protein vaccine, may broaden protection against invasive GBS disease.