Objectives: The objectives of the research were to determine which intravenous (IV) antibiotics were cost-effective in Diabetic Foot Infections (DFIs) and to assess the impact of MRSA prevalence on clinical outcome. Methods: A Cost-effectiveness analysis (CEA) was performed on IV antibiotics used to treat moderate to severe DFIs in hospitalized patients. MRSA prevalence was taken into account by calculating an ‘Adjusted cure rate’ and re-analysing the CEA. Results: In the original CEA, imipenem/cilastatin was the cost-effective agent. When MRSA prevalence was taken into account imipenem/cilastatin, moxifloxacin, cefoxitin and ertapenem were cost-effective antibiotics. Conclusion: MRSA prevalence adjustments changed the results of the CEA and included classes of IV antibiotics that are seen being using in practice, such as fluoroquinolones and cephalosporins. These methods could potentially have an impact on the evaluation of clinical cure rates and resistance when evaluating the literature.

Objectives: The objectives of the research were to determine which intravenous (IV) antibiotics were cost-effective in Diabetic Foot Infections (DFIs) and to assess the impact of MRSA prevalence on clinical outcome. Methods: A Cost-effectiveness analysis (CEA) was performed on IV antibiotics used to treat moderate to severe DFIs in hospitalized patients. MRSA prevalence was taken into account by calculating an ‘Adjusted cure rate’ and re-analysing the CEA. Results: In the original CEA, imipenem/cilastatin was the cost-effective agent. When MRSA prevalence was taken into account imipenem/cilastatin, moxifloxacin, cefoxitin and ertapenem were cost-effective antibiotics. Conclusion: MRSA prevalence adjustments changed the results of the CEA and included classes of IV antibiotics that are seen being using in practice, such as fluoroquinolones and cephalosporins. These methods could potentially have an impact on the evaluation of clinical cure rates and resistance when evaluating the literature.

The objective of the study was to determine whether diet diversity can predict the prevalence of infectious disease in children under 6-years in a rural African village. The study took place in Southern Madagascar. Dietary diversity, health and socio-economic interviews were administered to 77 mothers of children under 6 years old and who no longer breastfed. The diet diversity score was analysed along with socio-economic variables as predictors of the number of days a child had spent ill from an infectious disease in the past month. Meat and wild food variety, as well as education of the mother, childhood vaccinations and access to latrines and clean water were found to be important predictors of reduced disease risk in children. The study identifies conservation of natural resources and development of health and education facilities as priorities for the reduction of child mortality from infectious disease.

Human Cytomegalovirus (HCMV) is the most common cause of congenital infection in newborns. One mechanism for this virus to reach the fetus is to cross the placenta through the syncytiotrophoblast layer. Accumulation and protection of pathogens in the syncytiotrophoblast could affect the systemic distribution of pathogens and prolong maternal infections leading to increased incidence of fetal infections. Primary infections, reactivation or reinfection with another strain during pregnancy are risk factors for intrauterine HCMV transmission to the fetus. All lead to an active infection; however, viral load in blood or urine does not correlate with intrauterine transmission. I have shown that HCMV reversibly binds to the syncytiotrophoblast in vitro, protecting it from degradation. Furthermore, I demonstrated in vivo that HCMV is present in the placenta, even when cleared from maternal blood and urine. This evidence suggests increased potential for fetal transmission by virtue of continued virus localized at the maternal-fetal interface.

Thesis (Ph. D.)--University of Hawaii at Manoa, 1995. / Includes bibliographical references (leaves 120-131). / Microfiche. / xiii, 131 leaves, bound ill. 29 cm

Background: Street-involved youth are known to be at a greatly increased risk of HIV and sexually transmitted infections (STIs); however, the role that environmental and structural factors play in driving disease transmission risk among this population has not been thoroughly examined. Methods: The At Risk Youth Study (ARYS) is a prospective cohort of homeless and street-involved youth between the ages of 14 and 26. From September 2005 to October 2006, participants completed a baseline questionnaire which elicited information regarding sexual activity, injection and non-injection drug use, addiction treatment experience, encounters with police and security guards, and health service utilization. Environmental and structural correlates of number of recent sex partners were identified using quasi-Poisson regression. Factors independently associated with consistent condom use were also examined using logistic regression. Results: Among 529 participants, 415 (78.4%) were sexually active during the past six months, of whom 253 (61.0%) reported multiple sex partners and 288 (69.6%) reported inconsistent condom use during this time period. In multivariate logistic regression, homelessness and self-reported structural barriers to accessing health services were inversely associated with consistent condom use. In multivariate analysis, living in a shelter, hostel, or single room occupancy hotel was positively associated with greater numbers of recent sex partners. Structural factors that were associated with number of sex partners included having a warrant or area restriction that affects access to health services, and for males, being accosted by the police. Conclusions: Unstable housing, homelessness, and structural factors related to the criminalization and displacement of street-involved youth were associated with an increased risk of HIV and STI transmission, even after extensive adjustment for sociodemographic and individual level characteristics. These findings suggest that both environmental and structural factors influence the spread of HIV and STIs, and point to the need for environmental-structural interventions to reduce the burden of these diseases among this population.

The objectives of studies undertaken here were to identify the species of Colletotrichum associated with coffee berry anthracnose in PNG, gain an understanding of the infection process and factors affecting it, assess the impact, if any, of anthracnose on coffee quality and identify suitable chemicals for anthracnose control. A total of 40 isolates were collected from PNG and their cultural and morphological characteristics on PDA were studied and used to identify the species. Species identification was further confirmed by molecular characterisation using RFLP and DNA sequencing of the ITS region of the rDNA. After species identification only two isolates were selected to represent C. gloeosporioides and C. acutatum for further studies. Studies on conidia germination and the effects of conidia concentration, temperature, relative humidity and pH affecting germination were done on TWA, followed by studies on the infection process on coffee berries and the influence of temperature on germination and appressoria formation in vivo. For assessment of effect of anthracnose on coffee quality, 100 samples of ripe berries were assessed for disease incidence, followed by processing of the berries to green bean and data on bean defects (black bean) together with anthracnose incidence subjected to appropriate statistical analysis. A similar procedure was followed using disease severity but the samples were from one farm only. The closing work on chemical control was done by screening 16 different fungicides for the control of C. gloeosporioides and C. acutatum. With the 40 isolates, 29 were identified as C. gloeosporioides and 11 as C. acutatum. This is the first report of C. acutatum on coffee in PNG. Identification of the species was further confirmed by RFLP groupings where C. gloeosporioides and C. acutatum were separated at 574bp and 584bp respectively and DNA sequence homology identified the PNG isolates with C. gloeosporioides and C. acutatum accessions. Optimum conditions for conidia germination in relation to spore concentration, temperature, and pH are 1 x 106 spores/ml, 21 - 29°C and pH 5 - 7 respectively for C. acutatum and for C. gloeosporioides 1 x 106 spores/ml, 25 - 31°C and pH 5 - 7 respectively. Humidity is not a limiting factor for activity of both species. Infection process for both species is similar where conidia germinate to produce the germ tube which swells at the tip to form the appressoria. The appressoria produce an infection peg which is responsible for berry cuticle penetration and cell colonisation (resulting in typical anthracnose symptom expression) and eventual sporulation. C. acutatum has not been reported elsewhere as a pathogen of coffee and this is the first report of C. acutatum causing infections on both ripe and mature green berries. Anthracnose incidence did not correlate well with coffee bean defects, but anthracnose severity v suggested that coffee quality could be affected by anthracnose. The most effective fungicide for anthracnose control is thiram alone or thiram alternating with propiconazole.

In the well known SIR endemic model, the infection-free steady state is globally stable for R0 < 1 and unstable for R0 > 1. Hence, we have a forward bifurcation when R0 = 1. When R0 > 1, an asymptotically stable endemic steady state exists. The basic reproduction number R0 is the main threshold bifurcation parameter used to determine the stability of steady states of SIR endemic models. In this thesis we study extensions of the SIR endemic model for which a backward bifurcation may occur at R0 = 1. We investigate the biologically reasonable conditions for the change of stability. We also analyse the impact of di erent factors that lead to a backward bifurcation both numerically and analytically. A backward bifurcation leads to sub-critical endemic steady states and hysteresis. We also provide a general classi cation of such models, using a small amplitude expansion near the bifurcation. Additionally, we present a procedure for projecting three dimensional models onto two dimensional models by applying some linear algebraic techniques. The four extensions examined are: the SIR model with a susceptible recovered class; nonlinear transmission; exogenous infection; and with a carrier class. Numerous writers have mentioned that a nonlinear transmission function in relation to the infective class, can only lead to a system with an unstable endemic steady state. In spite of this we show that in a nonlinear transmission model, we have a function depending on the infectives and satisfying certain biological conditions, and leading to a sub-critical endemic equilibriums.

In the well known SIR endemic model, the infection-free steady state is globally stable for R0 < 1 and unstable for R0 > 1. Hence, we have a forward bifurcation when R0 = 1. When R0 > 1, an asymptotically stable endemic steady state exists. The basic reproduction number R0 is the main threshold bifurcation parameter used to determine the stability of steady states of SIR endemic models. In this thesis we study extensions of the SIR endemic model for which a backward bifurcation may occur at R0 = 1. We investigate the biologically reasonable conditions for the change of stability. We also analyse the impact of di erent factors that lead to a backward bifurcation both numerically and analytically. A backward bifurcation leads to sub-critical endemic steady states and hysteresis. We also provide a general classi cation of such models, using a small amplitude expansion near the bifurcation. Additionally, we present a procedure for projecting three dimensional models onto two dimensional models by applying some linear algebraic techniques. The four extensions examined are: the SIR model with a susceptible recovered class; nonlinear transmission; exogenous infection; and with a carrier class. Numerous writers have mentioned that a nonlinear transmission function in relation to the infective class, can only lead to a system with an unstable endemic steady state. In spite of this we show that in a nonlinear transmission model, we have a function depending on the infectives and satisfying certain biological conditions, and leading to a sub-critical endemic equilibriums.

Master of Science / The role of the microbiology laboratory is (1) to provide infection control information, so that highly transmissible isolates may be identified and appropriate control measures instigated as rapidly as possible and (2) to provide adequate information to the clinician enabling correct antibiotic choices to be made, particularly in the critically ill. Microbiological data is by definition slow as it is culture dependent: this study focused on the development of genetic, culture-independent methods for detection of resistance in nosocomial pathogens that could be introduced into the routine microbiology department and would fit into the routine workflow with a consequent reduction in time to result. Initially a duplex real-time polymerase chain reaction was developed for the rapid identification and detection of S. aureus and methicillin-resistance. This was optimised for immediate as-needs testing of positive blood cultures signalling with “Gram positive cocci, possibly staphylococcus” evident on Gram stain, on a random access real-time PCR platform. This technology, allowing early identification of S. aureus and its susceptibility to methicillin, by simple automated methodology, may soon become the standard for all microbiology laboratories servicing the critically ill. The second part of the study involved the development of a selective broth and multiplex PCR for detection of three important nosocomial isolates at this institution, methicillin-resistant S. aureus (MRSA), carbapenem-resistant Enterobacteriaceae, and multi-resistant Acinetobacter baumannii (MRAB). A multiplex PCR using four primer sets was designed to detect low colonisation levels of these isolates after overnight incubation in selective broth, significantly reducing the time to result and associated costs. This potentially useful epidemiological screening tool is practical, reproducible and sensitive with the potential of moving to an automated test (using real-time PCR, for example) in the future. The availability of early negative results judged by simple visual scanning (or by densitometry), means that the result is less operator-dependent, potentially reducing error rate. The last part of the study dealt with an important resistance phenotype, aminoglycoside resistance. There had been no recent comprehensive local surveys performed to determine the frequency of aminoglycoside resistance amongst the Enterobacteriaceae, or to identify the genetic determinants and their transmissibility. The isolates collected for the study were all resistant to at least one of gentamicin, tobramycin or amikacin. Identification of integron cassette arrays and use of specific internal primers identified at least one genetic determinant for gentamicin and tobramycin resistance in 22 of 23 isolates. Three isolates had two aminoglycoside resistance genes, and three isolates had three aminoglycoside resistance genes identified (Table 6.1). Transferable gentamicin-resistant plasmids were predominant amongst Klebsiella spp., but less so amongst Enterobacter spp. and E. coli. Gentamicin-resistant Klebsiella spp. were often ESBL positive, the genetic determinants of which were typically co-transferred on a conjugative plasmid. The importance of screening at a local level was demonstrated by the unexpected predominance of aac(6')-IIc amongst Enterobacter spp. and the detection of a new gene (aac(6')-LT). This part of the study has provided an understanding of the primary aminoglycoside resistance genes present in the local setting and their association with other resistances. This knowledge will allow development of assays for patient screening (clinical isolates and colonising flora), to better understand the epidemiology of aminoglycoside resistance and to allow better choice of antibiotic therapy related to presence or absence of these genes.