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      Immune responses to oral poliovirus vaccine in HIV-exposed uninfected Zimbabwean infants

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          ABSTRACT

          It remains uncertain whether HIV-exposed uninfected (HEU) infants have impaired responses to oral vaccines. We performed a cross-sectional study of 6-month-old infants recruited at birth to the ZVITAMBO trial in Zimbabwe between 1997–2001, before introduction of prevention of mother-to-child transmission interventions. We measured poliovirus-specific IgA to type 1–3 polio strains by semi-quantitative capture ELISA in cryopreserved serum samples collected from 85 HEU and 101 HIV-unexposed infants at 6 months of age, one month after their last immunisation with trivalent OPV. Almost all infants were breastfed, with the majority in both groups mixed breastfed (70.6% HEU versus 71.3% HIV-unexposed). Median (IQR) vaccine titers for HEU and HIV-unexposed infants were 1592 (618–4896) vs. 1774 (711–5431) for Sabin 1 ( P = 0.46); 1895 (810–4398) vs. 2308 (1081–4283) for Sabin 2 ( P = 0.52); and 1798 (774–4192) vs. 2260 (996–5723) for Sabin 3 ( P = 0.18). There were no significant differences in vaccine titers between HEU and HIV-unexposed infants, suggesting that vertical HIV exposure does not impact oral poliovirus vaccine immunogenicity.

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          Child mortality according to maternal and infant HIV status in Zimbabwe.

          Edmore Marinda, Jean Humphrey, Peter J Iliff … (2007)
          HIV causes substantial mortality among African children but there is limited data on how this is influenced by maternal or infant infection status and timing. Children enrolled in the ZVITAMBO trial were divided into 5 groups: those born to HIV-negative mothers (NE, n = 9510), those born to HIV-positive mothers but noninfected (NI, n = 3135), those infected in utero (IU, n = 381), those infected intrapartum (IP, n = 508), and those infected postnatally (PN, n = 258). Their mortality was estimated. Two-year mortality was 2.9% (NE infants), 9.2% (NI), 67.5% (IU), 65.1% (IP), and 33.2% (PN). Between 8 weeks and 6 months, mortality in IU infants quintupled (from 309 to 1686/1000 c-y). The median time from infection to death was 208, 380, and >500 days for IU, IP, and PN infants, respectively. Among NI children, advanced maternal disease was predictive of mortality. Acute respiratory infection was the major cause of death. Perinatally infected infants are at particular risk of death between 2 and 6 months: cotrimoxazole prophylaxis and early pediatric HAART should be scaled up. Uninfected infants of infected mothers have at least twice the mortality risk of infants born to uninfected mothers: all HIV-exposed infants should be targeted with child survival interventions. HIV-positive mothers with more advanced disease are not only more likely to infect their infants, but their infants are more likely to die, whether infected or not: provision of antiretroviral treatment to pregnant and lactating women is an urgent need for both mothers and their children.
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            Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival.

            K. Nathoo, Jeffrey J. Iliff, Lawrence Moulton … (2005)
            The promotion of exclusive breastfeeding (EBF) to reduce the postnatal transmission (PNT) of HIV is based on limited data. In the context of a trial of postpartum vitamin A supplementation, we provided education and counseling about infant feeding and HIV, prospectively collected information on infant feeding practices, and measured associated infant infections and deaths. A total of 14 110 mother-newborn pairs were enrolled, randomly assigned to vitamin A treatment group after delivery, and followed for 2 years. At baseline, 6 weeks and 3 months, mothers were asked whether they were still breastfeeding, and whether any of 22 liquids or foods had been given to the infant. Breastfed infants were classified as exclusive, predominant, or mixed breastfed. A total of 4495 mothers tested HIV positive at baseline; 2060 of their babies were alive, polymerase chain reaction negative at 6 weeks, and provided complete feeding information. All infants initiated breastfeeding. Overall PNT (defined by a positive HIV test after the 6-week negative test) was 12.1%, 68.2% of which occurred after 6 months. Compared with EBF, early mixed breastfeeding was associated with a 4.03 (95% CI 0.98, 16.61), 3.79 (95% CI 1.40-10.29), and 2.60 (95% CI 1.21-5.55) greater risk of PNT at 6, 12, and 18 months, respectively. Predominant breastfeeding was associated with a 2.63 (95% CI 0.59-11.67), 2.69 (95% CI 0.95-7.63) and 1.61 (95% CI 0.72-3.64) trend towards greater PNT risk at 6, 12, and 18 months, compared with EBF. EBF may substantially reduce breastfeeding-associated HIV transmission.
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              HIV-exposed, uninfected infants: new global challenges in the era of paediatric HIV elimination.

              Ceri Evans, Christine Jones, Andrew J. Prendergast (2016)
              The number of infants infected with HIV is declining with the rise in interventions for the elimination of paediatric HIV infection, but the number of uninfected infants exposed to HIV through their HIV-infected mothers is increasing. Interest in the health outcomes of HIV-exposed, uninfected infants has grown in the past decade, with several studies suggesting that these infants have increased mortality rates, increased infectious morbidity, and impaired growth compared with HIV-unexposed infants. However, heterogeneous results might reflect the inherent challenges in studies of HIV-exposed, uninfected infants, which need large populations with appropriate, contemporaneous comparison groups and repeated HIV testing throughout the period of breastfeeding. We review the effects of HIV exposure on mortality, morbidity, and growth, discuss the immunological abnormalities identified so far, and provide an overview of interventions that could be effective in this susceptible population. As the number of infants infected with HIV declines, the health needs of HIV-exposed, uninfected infants should be prioritised further, to ensure that post-2015 Sustainable Development Goals are achieved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Hum Vaccin Immunother
                Journal ID (iso-abbrev): Hum Vaccin Immunother
                Journal ID (publisher-id): KHVI
                Journal ID (publisher-id): khvi20
                Title: Human Vaccines & Immunotherapeutics
                Publisher: Taylor & Francis
                ISSN (Print): 2164-5515
                ISSN (Electronic): 2164-554X
                Publication date Collection: November 2017
                Publication date (Electronic): 31 August 2017
                Publication date PMC-release: 31 August 2017
                Volume: 13
                Issue: 11
                Pages: 2543-2547
                Affiliations
                [a ]Zvitambo Institute for Maternal and Child Health Research , Harare, Zimbabwe
                [b ]Blizard Institute, Queen Mary University of London , London, UK
                [c ]Department of Medicine, Vaccine Testing Center, University of Vermont , Burlington, VT, USA
                [d ]Department of International Health, Johns Hopkins Bloomberg School of Public Health , Baltimore, MD, USA
                Author notes
                CONTACT Dr James A. Church j.church@ 123456qmul.ac.uk Centre for Genomics and Child Health, Blizard Institute , Newark Street, London E1 2AT, UK
                Article
                Publisher ID: 1359454
                DOI: 10.1080/21645515.2017.1359454
                PMC ID: 5703368
                PubMed ID: 28857649
                SO-VID: 86f226ba-e6e1-4ed6-919e-514332e78bcf
                Copyright © © 2017 The Author(s). Published with license by Taylor & Francis
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 15 May 2017
                Date revision received : 28 June 2017
                Date accepted : 21 July 2017
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 36, Pages: 5
                Categories
                Subject: Short Report

                ScienceOpen disciplines: Molecular medicine
                Keywords: africa,hiv,infants,poliovirus,oral vaccine,opv
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: africa, hiv, infants, poliovirus, oral vaccine, opv

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