The global distribution and diversity of protein vaccine candidate antigens in the highly virulent Streptococcus pnuemoniae serotype 1

Serotype 1 is one of the most common causes of pneumococcal disease worldwide. Pneumococcal protein vaccines are currently being developed as an alternate intervention strategy to pneumococcal conjugate vaccines. Pre-requisites for an efficacious pneumococcal protein vaccine are universal presence and minimal variation of the target antigen in the pneumococcal population, and the capability to induce a robust human immune response. We used in silico analysis to assess the prevalence of seven protein vaccine candidates (CbpA, PcpA, PhtD, PspA, SP0148, SP1912, SP2108) among 445 serotype 1 pneumococci from 26 different countries, across four continents. CbpA (76%), PspA (68%), PhtD (28%), PcpA (11%) were not universally encoded in the study population, and would not provide full coverage against serotype 1. PcpA was widely present in the European (82%), but not in the African (2%) population. A multi-valent vaccine incorporating CbpA, PcpA, PhtD and PspA was predicted to provide coverage against 86% of the global population. SP0148, SP1912 and SP2108 were universally encoded and we further assessed their predicted amino acid, antigenic and structural variation. Multiple allelic variants of these proteins were identified, different allelic variants dominated in different continents; the observed variation was predicted to impact the antigenicity and structure of two SP0148 variants, one SP1912 variant and four SP2108 variants, however these variants were each only present in a small fraction of the global population (<2%). The vast majority of the observed variation was predicted to have no impact on the efficaciousness of a protein vaccine incorporating a single variant of SP0148, SP1912 and/or SP2108 from S. pneumoniae TIGR4. Our findings emphasise the importance of taking geographic differences into account when designing global vaccine interventions and support the continued development of SP0148, SP1912 and SP2108 as protein vaccine candidates against this important pneumococcal serotype

Infrastructure Planning in Rural Massachusetts

This paper describes the importance of understanding and dealing with the problems of infrastructure planning and maintenance in rural communities. Infrastructure is defined to include roads, bridges, water and wastewater collection and treatment systems, and public buildings and capital equipment. The authors base their findings primarily on the experience of communities in Massachusetts, but these findings are readily applied to the situation of rural communities elsewhere in the U.S.A. and other developed countries. Three major conclusions are presented in the paper: the need for rural communities to develop long-range plans for infrastructure maintenance and finance; the need to develop effective local institutions to assume this responsibility, and the importance of managing growth in fast-growing rural areas in order to minimize the need for major expansion of infrastructure systems

Dealing with Change in the Connecticut River Valley: A Design Manual for Conservation and Development

In a cooperative project between the Massachusetts Department of Environmental Management and the University of Massachusetts Amherst, Center for Rural Massachusetts, the authors addressed growth management and conservation strategies for the Connecticut River Valley. Nineteen towns and cities along the Connecticut River in Massachusetts were involved in the project, to develop practical planning and design standards to balance community preservation and future development. This critically acclaimed manual used striking perspective drawings, plans and photos to explain how any community can use creative planning guidelines to accommodate growth while preserving rural landscapes

Dealing with Change in the Connecticut River Valley - Volume 1

In 1986 the Center for Rural Massachusetts was created, and with it this project was begun. Funded by the Massachusetts Department of Environmental Management, the goal was to identify the critical character and qualities of Connecticut River Valley communities and identify new ways in which development could take place, but reduce its impact on the social, cultural, environmental and agricultural resources of the Valley.Volume 1 was published as the executive summary of the project, detailing the need for such an effort at a time when concern for rampant development was beginning to form into the sustainable development ideals of the 1990\u27s

Rural by Design

A revised and expanded edition of the 1988 book Dealing with Change in the Connecticut River Valley, the book delves deeply into the questions of rural development and what communities can do to manage growth

Dealing with Change in the Connecticut River Valley: A Design Manual for Conservation and Development

In a cooperative project between the Massachusetts Department of Environmental Management and the University of Massachusetts Amherst, Center for Rural Massachusetts, the authors addressed growth management and conservation strategies for the Connecticut River Valley. Nineteen towns and cities along the Connecticut River in Massachusetts were involved in the project, to develop practical planning and design standards to balance community preservation and future development. This critically acclaimed manual used striking perspective drawings, plans and photos to explain how communities could use creative planning guidelines to accommodate growth while preserving rural landscapes.Originally published in January 1988, it was published by the Lincoln Institute of Land Policy and the Environmental Law Foundation in June of 1988 and went through 5 printings between 1988 and 1993. It was revised and expanded and published by the American Planning Association as Rural by Design in 1994

Population biology of Streptococcus pneumoniae in West Africa: multilocus sequence typing of serotypes that exhibit different predisposition to invasive disease and carriage.

BACKGROUND: Little is known about the population biology of Streptococcus pneumoniae in developing countries, although the majority of pneumococcal infections occur in this setting. The aim of the study was to apply MLST to investigate the population biology of S. pneumoniae in West Africa. METHODS: Seventy three invasive and carriage S. pneumoniae isolates from three West African countries including The Gambia, Nigeria and Ghana were investigated. The isolates covered seven serotypes (1, 3, 5, 6A, 11, 14, 23F) and were subjected to multilocus sequence typing and antibiotic susceptibility testing. RESULTS: Overall, 50 different sequence types (STs) were identified, of which 38% (29) were novel. The most common ST was a novel clone-ST 4012 (6.5%), and some clones including STs 913, 925, 1737, 2160 and 3310 appeared to be specific to the study region. Two STs including ST 63 and ST 4012 were associated with multiple serotypes indicating a history of serotype switching. ST 63 was associated with serotypes 3 and 23F, while ST 4012 was associated with serotypes 6A and 23. eBURST analyses using the stringent 6/7 identical loci definition grouped the 50 STs into 5 clonal complexes and 65 singletons, expressing a high level of genetic diversity among the isolates. Compared to the other serotypes, serotypes 1 and 5 isolates appeared to be more clonal. Internationally recognized antibiotic resistant clones of S. pneumoniae were generally absent in the population investigated and the only multidrug resistant isolate identified (1/66) belong to the Pneumocococcal Epidemiology Network clone ST 63. CONCLUSIONS: The pneumococcal population in West Africa is quite divergent, and serotypes that are common in invasive disease (such as serotypes 1 and 5) are more likely to be clonal than serotypes that are common in carriage