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      Longitudinal analysis of antibody responses to trachoma antigens before and after mass drug administration

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          Abstract

          Background

          Blinding trachoma, caused by the bacteria Chlamydia trachomatis, is a neglected tropical disease targeted for elimination by 2020. A major component of the elimination strategy is mass drug administration (MDA) with azithromycin. Currently, program decisions are made based on clinical signs of ocular infection, but we have been investigating the use of antibody responses for post-MDA surveillance. In a previous study, IgG responses were detected in children lacking clinical evidence of trachoma, suggesting that IgG responses represented historical infection. To explore the utility of serology for program evaluation, we compared IgG and IgA responses to trachoma antigens and examined changes in IgG and IgA post-drug treatment.

          Methods

          Dried blood spots and ocular swabs were collected with parental consent from 264 1–6 year olds in a single village of Kongwa District, central Tanzania. Each child also received an ocular exam for detection of clinical signs of trachoma. MDA was given, and six months later an additional blood spot was taken from these same children. Ocular swabs were analyzed for C. trachomatis DNA and antibody responses for IgA and total IgG were measured in dried bloods spots.

          Results

          Baseline antibody responses showed an increase in antibody levels with age. By age 6, the percentage positive for IgG (96.0%) was much higher than for IgA (74.2%). Antibody responses to trachoma antigens declined significantly six months after drug treatment for most age groups. The percentage decrease in IgA response was much greater than for IgG. However, no instances of seroreversion were observed.

          Conclusions

          Data presented here suggest that focusing on concordant antibody responses in children will provide the best serological surveillance strategy for evaluation of trachoma control programs.

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          Most cited references18

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          A simple system for the assessment of trachoma and its complications.

          A simple grading system for trachoma, based on the presence or absence of five selected "key" signs, has been developed. The method was tested in the field and showed good observer agreement, the most critical point being the identification of severe cases of the disease. It is expected that the system will facilitate the assessment of trachoma and its complications by non-specialist health personnel working at the community level.
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            Duration of antiviral immunity after smallpox vaccination.

            Although naturally occurring smallpox was eliminated through the efforts of the World Health Organization Global Eradication Program, it remains possible that smallpox could be intentionally released. Here we examine the magnitude and duration of antiviral immunity induced by one or more smallpox vaccinations. We found that more than 90% of volunteers vaccinated 25-75 years ago still maintain substantial humoral or cellular immunity (or both) against vaccinia, the virus used to vaccinate against smallpox. Antiviral antibody responses remained stable between 1-75 years after vaccination, whereas antiviral T-cell responses declined slowly, with a half-life of 8-15 years. If these levels of immunity are considered to be at least partially protective, then the morbidity and mortality associated with an intentional smallpox outbreak would be substantially reduced because of pre-existing immunity in a large number of previously vaccinated individuals.
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              Cutting edge: long-term B cell memory in humans after smallpox vaccination.

              Memory B cells are a central component of humoral immunity, and yet little is known about their longevity in humans. Immune memory after smallpox vaccination (DryVax) is a valuable benchmark for understanding the longevity of B cell memory in the absence of re-exposure to Ag. In this study, we demonstrate that smallpox vaccine-specific memory B cells last for >50 years in immunized individuals. Virus-specific memory B cells initially declined postimmunization, but then reached a plateau approximately 10-fold lower than peak and were stably maintained for >50 years after vaccination at a frequency of approximately 0.1% of total circulating IgG(+) B cells. These persisting memory B cells were functional and able to mount a robust anamnestic Ab response upon revaccination. Additionally, virus-specific CD4(+) T cells were detected decades after vaccination. These data show that immunological memory to DryVax vaccine is long-lived and may contribute to protection against smallpox.
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                Author and article information

                Contributors
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2014
                22 April 2014
                : 14
                : 216
                Affiliations
                [1 ]Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA
                [2 ]The Ohio State University College of Optometry, Columbus, OH, USA
                [3 ]St. Olaf College, Northfield, MN, USA
                [4 ]Dana Center for Preventative Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA
                [5 ]Center for Infectious Diseases, Johns Hopkins University, Baltimore, MD, USA
                [6 ]Kongwa Trachoma Project, Kongwa, United Republic of Tanzania
                Article
                1471-2334-14-216
                10.1186/1471-2334-14-216
                4016634
                24755001
                352757cf-923e-4075-8e97-e3eb219c9f28
                Copyright © 2014 Goodhew et al.; licensee BioMed Central Ltd.

                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 credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 February 2014
                : 9 April 2014
                Categories
                Research Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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