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The anaerobic spirochaete Brachyspira pilosicoli causes enteric disease in avian, porcine and human hosts, amongst others. Avian intestinal spirochaetosis (AIS), the resulting disease from colonisation of the caeca and colon of poultry by Brachyspira , leads to production losses, with an estimated annual cost of circa £ 18 million to the commercial layer industry in the United Kingdom. A lack of knowledge of the metabolic capabilities and little genomic information for Brachyspira has resulted in a limited understanding of the pathobiology of this genus. In addition, an emergence of antibiotic resistance in Brachyspira, together with bans on the prophylactic use of antimicrobials in animal feed, drive an urgent requirement for alternative treatment strategies for diseases such as AIS. In the first intra-species genome comparison within the genus Brachyspira, these studies report the whole genome sequence of an avian strain of B. pilosicoli, B2904, and the incomplete genome sequence of a human strain of B. pilosicoli, WesB. Comparisons are made between the de novo sequenced strains and those of B. pilosicoli 95/1 000, a pig strain and other available Brachyspira genome sequences from public databases. Furthermore, this study reports the first application of the high-throughput Biolog phenotype screening tool to Brachyspira for detailed phenotypic analysis and confirmation of metabolic deductions made from the genotypic data. Probiotics have been reported as protecting against infection with common enteric pathogens in livestock and in this study investigations into which aspects of the biology of Brachyspira they antagonise were undertaken. Lactobacilli reduced the growth and motility of B. pilosicoli and its ability to adhere and invade epithelial cells in vitro. Following these encouraging results, an in vivo intervention study was performed using a B. pilosicoli challenge model in poultry to elucidate the potential for probiotic intervention against AIS. This study demonstrated that when administered in drinking water, L. reuteri LM 1, isolated from a healthy chicken, reduced all aspects of the clinical presentation of AIS.

Typhoid fever remains an important public health problem globally. Cluster randomized effectiveness trials with typhoid Vi polysaccharide vaccine were conducted in Kolkata, India and Karachi, Pakistan, to provide evidence for vaccine introduction. While efficacy trials are limited to estimate vaccine's performance on the vaccine recipients, effectiveness trials consider the public health impact, notably the herd protection, or indirect effect, which can only be seen when vaccines are administered to groups rather than to individuals. The observed total protection by the Vi polysaccharide vaccine in school-aged children was consistent in Kolkata and Karachi (61% and 56%, respectively), and was associated with minimal side-effects. The total protection in young children, however, was different (80% in Kolkata and no protection in Karachi). The Kolkata trial demonstrated significant herd protective effects, as demonstrated by indirect protection of non-vaccinees (45%), which was not shown in the Karachi trial. The difference in the effectiveness estimates between the trials may be due to the difference in study design and the population characteristics. Immunogenicity studies were undertaken for randomly selected persons from both sites at pre-vaccination, 6 weeks, and 2 years post-vaccination. Serum Vi antibody titres (IgG) were measured through ELISA. At baseline, the GMTs were below the protective level for both sites. At six weeks after vaccination, though there is a significant increase in the GMTs in children from both site, the level of GMTs were significantly lower from those in Karachi (2,307.0 ELU vs. 1,189.1 ELU). GMT declined from 6 week to 2 year testing points for both sites but maintained the protective level. These effectiveness trials gave a conclusive evidence of the protection conferred by the Vi polysaccharide vaccine in children older than 5 years of age. Targeted vaccination programme in high endemic areas, as stipulated in the WHO Position Paper, suggest the potential for effective control of typhoid fever in places like India and Pakistan with the school-based Vi vaccination.