title: Longitudinal analysis of antibody responses to trachoma antigens before and after mass drug administration.
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.
authors.forename: Erica Brook
authors.initials: EB
authors.lastname: Goodhew
authors.forename: Sheri Maria G
authors.initials: SM
authors.lastname: Morgan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Switzer
authors.forename: Beatriz
authors.initials: B
authors.lastname: Munoz
authors.forename: Laura
authors.initials: L
authors.lastname: Dize
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gaydos
authors.forename: Harran
authors.initials: H
authors.lastname: Mkocha
authors.forename: Sheila K
authors.initials: SK
authors.lastname: West
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Wiegand
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Lammie
authors.affiliation: Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA. hzx3@cdc.gov.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Martin
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000917:Antibody Formation; D017963:Azithromycin / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000032:analysis; D005123:Eye / Q000378:metabolism; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D013636:Tanzania / Q000453:epidemiology; D014141:Trachoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D017963:Azithromycin
references.citation: J Immunol. 2003 Nov 15;171(10):4969-73
references.pmid: 14607890
references.citation: J Clin Microbiol. 2013 May;51(5):1611-3
references.pmid: 23486714
references.citation: PLoS Negl Trop Dis. 2011 Dec;5(12):e1408
references.pmid: 22206024
references.citation: J Clin Microbiol. 1983 Jul;18(1):1-4
references.pmid: 6885981
references.citation: Invest Ophthalmol Vis Sci. 2011 Nov 11;52(12):8806-10
references.pmid: 22025578
references.citation: J Clin Pathol. 1997 Oct;50(10):819-22
references.pmid: 9462262
references.citation: Am J Trop Med Hyg. 2003 Nov;69(5 Suppl):33-5
references.pmid: 14692679
references.citation: Am J Trop Med Hyg. 2011 Aug;85(2):229-37
references.pmid: 21813840
references.citation: Immunol Rev. 2012 Jan;245(1):132-46
references.pmid: 22168417
references.citation: Biostatistics. 2010 Apr;11(2):373-4
references.pmid: 19948745
references.citation: Nature. 1997 Jul 10;388(6638):133-4
references.pmid: 9217150
references.citation: Nat Med. 2003 Sep;9(9):1131-7
references.pmid: 12925846
references.citation: Clin Exp Immunol. 2008 Jan;151(1):42-50
references.pmid: 18005364
references.citation: PLoS Negl Trop Dis. 2012 Jan;6(1):e1479
references.pmid: 22272369
references.citation: BMC Med Res Methodol. 2001;1:6
references.pmid: 11459516
references.citation: Diagn Microbiol Infect Dis. 2013 Dec;77(4):289-91
references.pmid: 24079951
references.citation: Nature. 2000 Oct 5;407(6804):636-42
references.pmid: 11034213
references.citation: PLoS Negl Trop Dis. 2012;6(11):e1873
references.pmid: 23133684
references.citation: N Engl J Med. 2007 Nov 8;357(19):1903-15
references.pmid: 17989383
references.citation: Nature. 2008 Sep 25;455(7212):532-6
references.pmid: 18716625
references.citation: Immunol Rev. 2006 Jun;211:320-37
references.pmid: 16824139
references.citation: Eur J Clin Microbiol Infect Dis. 1988 Jun;7(3):388-93
references.pmid: 3137040
references.citation: Epidemiol Infect. 1999 Dec;123(3):479-86
references.pmid: 10694161
references.citation: Bull World Health Organ. 1987;65(4):477-83
references.pmid: 3500800
references.citation: Br J Ophthalmol. 2009 May;93(5):563-8
references.pmid: 19098034