The GOAL of this research is to establish a scientific basis for cost effective prevention of conjunctivitis. Bacterial conjunctivitis is a costly diseaseof children. There are > 4 million office visits in the US/yr. Among the most common infections of childhood, it is a leading cause for antibiotic use. Half of cases occur in children under 9 years, with an annual cost of over $500 million. Bacterial conjunctivitis is caused by unusual strains of unencapsulated S. pneumoniae that are largely incapable of causing disease at other body sites and are uniquely pathogenic for the eye. Falling between specialties of Ophthalmology and Infectious Diseases, these unusual microbes have largely gone unstudied. An especially large and well documented conjunctivitis outbreak, involving 698 students at Dartmouth College, and six months later, the same strain caused another outbreak among 101 young children and 120 family contacts in Maine. Vaccines target the primary virulence factor of S. pneumoniae - the capsule. However, the vaccine is completely ineffective in preventing conjunctivitis, a disease uniquely caused by strains that lack the capsule, leaving an unaddressed gap in coverage. If we understood the basis for the unusual tropism of unencapsulated pneumococci for the ocular surface - that is, the key factors allowing it to bind and colonize the eye - we could include epitopes of these factors in the vaccine already being used, thereby preventing a common disease of childhood, and saving hundreds of $ million in health care costs, and limiting a leading cause for treating children with antibiotics, which is now believed to be altering their flra as well as leading to antibiotic resistance. In preliminary studies, we undertook an expansive comparative genomics study to identify candidate factors that allow unencapsulated S. pneumoniae to bind to the ocular surface. This research proposes to follow up these leads by directly testing a prioritized list of the most strongly implicated adhesins and other colonization factors, for their ability to mediate attachment to the ocular surface. The proposed studies combine biological approaches, as well as state-of-the-art genomics approaches, to identify the most important colonization factors that lead to conjunctivitis.

Public Health Relevance

Bacterial conjunctivitis, a common disease of children, adds over $ 500 million/yr to health care costs and is a leading cause for childhood use of antibiotics. A leading cause for this disease, S.pneumoniae, is completely missed by the vaccine because of the unusual properties of these eye-specific strains. This work aims to identify properties that could make the existing vaccine effective for prevent ocular infections as well.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY024285-04
Application #
9264533
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Mckie, George Ann
Project Start
2014-05-01
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2019-04-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
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Zhai, Hualei; Bispo, Paulo J M; Kobashi, Hidenaga et al. (2018) Resolution of fluoroquinolone-resistant Escherichia coli keratitis with a PROSE device for enhanced targeted antibiotic delivery. Am J Ophthalmol Case Rep 12:73-75
Wurster, Jenna I; Bispo, Paulo J M; Van Tyne, Daria et al. (2018) Staphylococcus aureus from ocular and otolaryngology infections are frequently resistant to clinically important antibiotics and are associated with lineages of community and hospital origins. PLoS One 13:e0208518
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