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HIV-Infected Children Living in Central Africa Have Low Persistence of Antibodies to Vaccines Used in the Expanded Program on Immunization

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      Abstract

      Background

      The Expanded Program on Immunization (EPI) is the most cost-effective measures to control vaccine-preventable diseases. Currently, the EPI schedule is similar for HIV-infected children; the introduction of antiretroviral therapy (ART) should considerably prolong their life expectancy.

      Methods and Principal Findings

      To evaluate the persistence of antibodies to the EPI vaccines in HIV-infected and HIV-exposed uninfected children who previously received these vaccines in routine clinical practice, we conducted a cross-sectional study of children, aged 18 to 36 months, born to HIV-infected mothers and living in Central Africa. We tested blood samples for antibodies to the combined diphtheria, tetanus, and whole-cell pertussis (DTwP), the measles and the oral polio (OPV) vaccines. We enrolled 51 HIV-infected children of whom 33 were receiving ART, and 78 HIV-uninfected children born to HIV-infected women. A lower proportion of HIV-infected children than uninfected children had antibodies to the tested antigens with the exception of the OPV types 1 and 2. This difference was substantial for the measles vaccine (20% of the HIV-infected children and 56% of the HIV-exposed uninfected children, p<0.0001). We observed a high risk of low antibody levels for all EPI vaccines, except OPV types 1 and 2, in HIV-infected children with severe immunodeficiency (CD4+ T cells <25%).

      Conclusions and Significance

      Children were examined at a time when their antibody concentrations to EPI vaccines would have still not undergone significant decay. However, we showed that the antibody concentrations were lowered in HIV-infected children. Moreover, antibody concentration after a single dose of the measles vaccine was substantially lower than expected, particularly low in HIV-infected children with low CD4+ T cell counts. This study supports the need for a second dose of the measles vaccine and for a booster dose of the DTwP and OPV vaccines to maintain the antibody concentrations in HIV-infected and HIV-exposed uninfected children.

      Related collections

      Most cited references 43

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      Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis.

      HIV contributes substantially to child mortality, but factors underlying these deaths are inadequately described. With individual data from seven randomised mother-to-child transmission (MTCT) intervention trials, we estimate mortality in African children born to HIV-infected mothers and analyse selected risk factors. Early HIV infection was defined as a positive HIV-PCR test before 4 weeks of age; and late infection by a negative PCR test at or after 4 weeks of age, followed by a positive test. Mortality rate was expressed per 1000 child-years. We investigated the effect of maternal health, infant HIV infection, feeding practices, and age at acquisition of infection on mortality assessed with Cox proportional hazards models, and allowed for random effects for trials grouped geographically. 378 (11%) of 3468 children died. By age 1 year, an estimated 35.2% infected and 4.9% uninfected children will have died; by 2 years of age, 52.5% and 7.6% will have died, respectively. Mortality varied by geographical region, and was associated with maternal death (adjusted odds ratio 2.27, 95% CI 1.62-3.19), CD4+ cell counts <200 per microL (1.91, 1.39-2.62), and infant HIV infection (8.16, 6.43-10.33). Mortality was not associated with either ever breastfeeding and never breastfeeding in either infected or uninfected children. In infected children, mortality was significantly lower for those with late infection than those with early infection (0.52, 0.39-0.70). This effect was also seen in analyses of survival from the age at infection (0.74, 0.55-0.99). These findings highlight the necessity for timely antiretroviral care, for support for HIV-infected women and children in developing countries, and for assessment of prophylactic programmes to prevent MTCT, including child mortality and infection averted.
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        HIV disease: fallout from a mucosal catastrophe?

        The pathogenesis of human immunodeficiency virus has long been thought to center on a gradual depletion of CD4(+) T cells, with an average of 100 cells lost per microliter of blood per year. However, studies of macaques infected with simian immunodeficiency virus and humans infected with human immunodeficiency virus have shown that the infection rapidly kills most CD4(+) T cells at mucosal surfaces. Although most CD4(+) T cells reside at these sites, the magnitude of this assault on the immune system is not reflected in the peripheral blood. Here we consider models of human immunodeficiency virus disease pathogenesis given those findings and propose a hypothesis to account for particular aspects of the disease during the chronic phase of infection that can be directly attributed to early depletion of mucosal CD4(+) T cells.
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          Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African children: a prospective descriptive study.

          HIV-related pneumonia is the main cause of paediatric hospital admissions in southern Africa. We aimed to measure predictors of treatment failure and the cause of non-responsive pneumonia in children admitted to hospital with severe pneumonia in Durban, South Africa. We investigated 358 children aged 1-59 months who presented with WHO-defined severe or very severe pneumonia. Children were recruited irrespective of HIV status and started on a standard antimicrobial regimen of benzylpenicillin and gentamicin. All infants also received high-dose trimethoprim-sulfamethoxazole. The primary outcome measure was treatment failure at 48 h. 242 (68%) children were HIV infected, 41 (12%) HIV exposed, uninfected, and 75 (21%) HIV uninfected. Failure to respond by 48 h was predicted by age under 1 year (adjusted odds ratio 6.38, 95% CI 2.72-14.91, p<0.0001), very severe disease (2.47, 1.17-5.24, p=0.0181), HIV status (HIV infected 10.3, 3.26-32.51; HIV exposed, uninfected 6.02, 1.55-23.38; p=0.0003), and polymicrobial disease (one organism 2.06, 1.05-4.05; two organisms 10.75, 4.38-26.36; p<0.0001) on logistic regression analysis. All children with three organisms failed treatment. 72/110 treatment failures had at least two organisms isolated. Three of nine HIV-exposed, uninfected infants, 29/74 HIV-infected, but no HIV-uninfected infants who failed study therapy had Pneumocystis jirovecii pneumonia. For children younger than 1 year, the WHO guidelines are inadequate and need to be revised since both HIV-infected and HIV-exposed, uninfected infants had more treatment failures than did HIV-uninfected infants. Polymicrobial disease is an important reason for treatment failure, and we need to identify rapid low-cost diagnostic methods to assist clinicians.
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            Author and article information

            Affiliations
            [1]Centre Pasteur du Cameroun, Laboratoire d'Epidémiologie et de Santé Publique, Yaoundé, Cameroun
            [2]Centre Pasteur du Cameroun, Laboratoire de Virologie, Yaoundé, Cameroun
            [3]Centre Pasteur du Cameroun, Laboratoire d'Analyses Médicales, Yaoundé, Cameroun
            [4]Institut Pasteur de Bangui, Laboratoire des Entérovirus, Bangui, Central African Republic
            [5]Institut Pasteur de Bangui, Laboratoire des Rétrovirus, Bangui, Central African Republic
            [6]Centre Mère et Enfant de la Fondation Chantal Biya, Yaoundé, Cameroun
            [7]Complexe Pédiatrique de Bangui, Central African Republic
            [8]Centre National de Référence des Bordetella, Institut Pasteur, Paris, France
            [9]Laboratoire de Génomique Virale et Vaccination, Institut Pasteur, Paris, France
            [10]Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France
            [11]Hôpital Laquintinie, Service de Pédiatrie, Douala, Cameroun
            University of Cape Town, South Africa
            Author notes
            * To whom correspondence should be addressed. E-mail: laurence_baril@123456yahoo.com

            Conceived and designed the experiments: LB MT IG. Performed the experiments: AK ME IG LB EN. Analyzed the data: RP LB MT. Contributed reagents/materials/analysis tools: FT DR CB. Wrote the paper: FT LB MT. Other: Wrote the first draft of the paper: LB. Recruitment and follow-up of the children: GT JC IP.

            Contributors
            Role: Academic Editor
            Journal
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, USA)
            1932-6203
            2007
            5 December 2007
            : 2
            : 12
            2093997
            18060056
            07-PONE-RA-01507R1
            10.1371/journal.pone.0001260
            (Academic Editor)
            TEJIOKEM et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
            Counts
            Pages: 8
            Categories
            Research Article
            Pediatrics and Child Health
            Immunology/Immune Response
            Virology/Immunodeficiency Viruses
            Virology/Vaccines
            Infectious Diseases/HIV Infection and AIDS
            Infectious Diseases/Viral Infections
            Public Health and Epidemiology/Immunization
            Public Health and Epidemiology/Infectious Diseases

            Uncategorized

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