The escalation of Long-Lasting Insecticidal Nets (LLINs) mass distribution marked the beginning of a period of malaria decline in sub-Saharan Africa. However, the emergence and spread of insecticide resistance in malaria mosquitoes is a threat to the effectiveness and sustainability of this vector control method. In this context, it is necessary to design and evaluate new compounds and methods that attenuate or even reverse the insecticide resistance trend. Olyset Duo is a novel LLIN that combines the insecticide properties of permethrin and the chemosterilising effect of pyriproxyfen (PPF). The rationale is that resistant mosquitoes that survive the contact with the net would not be able to transfer the resistance genes to the offspring, eventually influencing the resistant phenotype of the mosquito population. In the first part of this study the sterilising and sub-lethal effect of PPF and Olyset Duo was evaluated by a range of bioassays with laboratory and wild mosquito populations. PPF significantly affected the longevity, oogenesis, oviposition and hatching rate of susceptible and resistant mosquitoes, although the effect was partially diminished on the resistant colonies. The possible reasons and implications of PPF performance under controlled conditions are discussed. The second part of this thesis was done within the context of an Olyset Duo Randomised Controlled Trial (RCT) set in Banfora District, Burkina Faso. The RCT had a stepped-wedge design which ensured that Olyset Duo nets gradually replaced Olyset nets in randomly allocated cluster of villages until the Olyset Duo coverage was total. Wild mosquitoes collected in sentinel sites with Olyset Duo showed evident signs of reproductive impairment even after 1 year of deployment. Insecticide resistance strength was monitored during the RCT in several sentinel sites, and time-response data showed an overall reduction of permethrin resistance strength after the distribution of Olyset Duo. This is the most detailed study on the effect of Olyset Duo on key entomological factors of wild mosquito populations. The standardised protocols as well as the dataset obtained are valuable information for ongoing evaluation of Olyset Duo and PPF as a tool for controlling malaria mosquitoes and as a potential alternative for insecticide resistance management.

Seasonal influenza is a serious public health problem that can cause severe illness, hospitalisation and death. Influenza vaccination is one of the most effective methods for preventing influenza and its complications. In Hong Kong, people aged 50 to 64 were added as a recommended priority target group for influenza vaccination by the Department of Health starting from 2011/12. The coverage rate of the influenza vaccine for this age group was 8.5 percent in 2012/13. In order to explore the reasons for the low influenza vaccine coverage rate, a systematic literature review and a case-control study were conducted. The literature review aimed to explore what demographic, social and psychological factors were associated with the uptake of influenza vaccination among adults from 18 to 64 years. The result of the review was used to inform the design of a case-control study, which aimed to determine factors associated with the uptake of influenza vaccination amongst adults aged 50 to 64 years in Hong Kong. The literature review and the case-control study are presented in publication format. The case-control study was conducted using street intercept interviews from 17 July to 15 August 2013. Cases were adults aged 50 to 64 years who received influenza vaccination in 2011/12 or 2012/13, while controls were the same as cases, except they did not receive the vaccine during the same period. Multinomial logistic regression analysis was performed on the data to explore associations between vaccination status and the variables. The study had a total of 604 respondents: 193 cases (vaccinated) and 411 controls (non-vaccinated), with a case-to-control ratio of 1:2.1. The factors which possessed the strongest associations with influenza vaccination were: ‘eligible for free government vaccine’; ‘willing to receive flu vaccination for free’; ‘perceived having severe or moderately symptoms when contracting flu’; and ‘accept advice from health professional’.

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Geostatistical methods are increasingly used in low-resource settings where disease registries are either non-existent or geographically incomplete. In this thesis, which is comprised of four papers, we address some of the common issues that arise from analysing disease prevalence data. In the first paper we consider the problem of combining data from multiple spatially referenced surveys so as to account for two main sources of variation: temporal variation, when surveys are repeated over time; data-quality variation, e.g. between randomised and non-randomised surveys. We then propose a multivariate binomial geostatistical model for the combined analysis of data from multiple surveys. We also show an application to malaria prevalence data from three surveys conducted in two consecutive years in Chikwawa District, Malawi, one of which used a more economical convenience sampling strategy. In the second paper, we analyse river-blindness prevalence data from a survey conducted in 20 African countries enrolled in the African Programme of Onchocerciasis Control (APOC). The main challenge of this analysis is computational, as a binomial geostatistical model has to be fitted to more than 14,000 village locations and predictions carried out on about 10 millions locations across Africa. To make the computation feasible and efficient, we then develop a low rank approximation based on a convolution-kernel representation which avoids matrix inversion. The third paper is a tutorial on the use of a new R package, namely “PrevMap”, which provides functions for both likelihood-based and Bayesian analysis of spatially referenced prevalence data. In the fourth paper, we present some extensions of the standard geostatistical model for spatio-temporal analysis of prevalence data and modelling of spatially structured zero-inflation. We then describe three applications that have arisen through our collaborations with researchers and public health programmers in African countries.

Salmonella enteritidis continues to be a major cause of foodboume infections in the United Kingdom, the rest of Europe, and the USA with poultry implicated as a major source. To understand the virulence mechanisms of bacterial pathogens it is necessary to study directly host-bacterial interactions. For E. coli it is considered that adherence to enterocytes is a prerequisite to infection and the adhesive function of certain fimbriae have been described (Parry & Rooke, 1985). However, for Salmonella spp.the role of surface appendages is poorly understood. S. enteritidis express flagella and several tightly regulated fimbriae including SEF14 and SEF21 (type 1) that are morphologically and antigenically distinct. In addition, Collinson et al. (1991) demonstrated elaboration of aggregative SEF17 fimbriae by S. enteritidis 27655R, although conditions neccesary for expression of this surface appendage, other than strain 27655R, were unknown. In this study specific immunological reagents were raised to SEF17 and used to investigate the expression of SEF17 fimbriae by cultured strains of S. enteritidis. Elaboration of SEF17 was dependant upon temperature and media with optimal expression at 18°C on CFA agar. However, two wild type strains produced SEF17 when also grown at 30°C to 42°C. In addition, fine fimbriae produced by a strain of S. typhimurium and E. coli were specifically and strongly labelled by SEF17 monoclonal and polyclonal antibodies, indicating considerable antigenic conservation. A panel of mutants prepared in three strains of S. enteritidis defective for the elaboration of fimbrial types SEF14, SEF17, SEF21 and flagella were utilised to determine the role of these surface appendages in association with and invasion of cultured epithelial cells. In all assays, the naturally occuring regulatory defective strain 27655R associated to tissue culture cells significantly greater than LA5 and S1400. Compared with wild type progenitor strains, SEF14 mutants had no effect on association and invasion, whereas for both association and invasion, SEF17, SEF21 and aflagellate mutants showed significant reductions. Isogenic mutants prepared in a chicken isolate, S. enteritidis strain LA5, were used to study the contribution of these organelles in the colonisation, invasion, persistence and lateral transfer in young chicks. The caecum, liver and spleen were colonised within 24 hours following oral inoculation of day old chicks with 105 wild type S. enteritidis. SEF17, SEF21 and flagella contributed to a delay in colonisation of the spleen as did SEF21 and flagella mutants in the liver. Lower numbers of bacteria were recovered from the caecum with mutants deficient for SEF21 elaboration. LA5 and EAV40 (14', 17', 21', fla ) persisted for six weeks in the caecum and to a lesser extent the liver and spleen of birds. In addition, sentinel birds were colonised by LA5 or EAV40 directly from the environment within two days, although, a slight delay was observed with the multiple mutant. Overall, data from this study suggests that SEF17, SEF21 and flagella, but not SEF14, play a role in the early stages of colonisation and invasion of young chicks by S. enteritidis, but are unnecessary for S. enteritidis to persist for up to six weeks or colonise birds from their immediate environment.

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