Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: HIV infection is one of the world’s biggest health problems, with millions of people infected worldwide. HIV infects cells in the immune system, where it primarily targets CD4+ T helper cells and without treatment, the disease leads to the collapse of the host immune system and ultimately death. Mathematical models have been used extensively to study the epidemiology of HIV/AIDS. They have proven to be effective tools in studying the transmission dynamics of HIV. These models provide predictions that can help better our understanding of the epidemiological patterns of HIV, especially the mechanism associated with the spread of the disease. In this thesis we made a functional comparison between existing epidemiological models for HIV, with the focus of the comparison on the force of infection (FOI). The spread of infection is a crucial part of any infectious disease, as the dynamics of the disease depends greatly on the rate of transmission from an infectious individual to a susceptible individual. First, a review was done to see what deterministic epidemiological models exist. We found that many manuscripts do not provide the necessary information to recreate the authors’ results and only a small amount of the models could be simulated. The reason for this is mainly due to a lack of information or due to mistakes in the article. The models were divided into four categories for the analysis. On the basis of the FOI, we distinguished between frequency- or density-dependent transmission, and as a second criterion we distinguished models on the sexual activity of the AIDS group. Subsequently, the models were compared in terms of their FOI, within and between these classes. We showed that for larger populations, frequency-dependent transmission should be used. This is the case for HIV, where the disease is mainly spread through sexual contact. Inclusion of AIDS patients in the group of infectious individuals is important for the accuracy of transmission dynamics. More than half of the studies that were selected in the review assumed that AIDS patients are too sick to engage in risky sexual behaviour. We see that including AIDS patients in the infectious individuals class has a significant effect on the FOI when the value for the probability of transmission for an individual with AIDS is bigger than that of the other classes. The analysis shows that the FOI can vary depending on the parameter values and the assumptions made. Many models compress various parameter values into one, most often the transmission probability. Not showing the parameter values separately makes it difficult to understand how the FOI works, since there are unknown factors that have an influence. Improving the accuracy of the FOI can help us to better understand what factors influence it, and also produce more realistic results. Writing the probability of transmission as a function of the viral load can help to make the FOI more accurate and also help in the understanding of the effects that viral dynamics have on the population transmission dynamics. / AFRIKAANSE OPSOMMING: MIV-infeksie is een van die wêreld se grootste gesondheidsprobleme, met miljoene mense wat wêreldwyd geïnfekteer is. MIV infekteer selle in die immuunstelsel, waar dit hoofsaaklik CD4+ T-helperselle teiken. Sonder behandeling lei die siekte tot die ineenstorting van die gasheer se immuunstelsel en uiteindelik sy dood. Wiskundige modelle word breedvoerig gebruik om die epidemiologie van MIV/vigs te bestudeer. Die modelle is doeltreffende instrumente in die studie van die oordrag-dinamika van MIV. Hulle lewer voorspellings wat kan help om ons begrip van epidemiologiese patrone van MIV, veral die meganisme wat verband hou met die verspreiding van die siekte, te verbeter. In hierdie tesis het ons ‘n funksionele vergelyking tussen bestaande epidemiologiese modelle vir MIV gedoen, met die fokus van die vergelyking op die tempo van infeksie (TVI). Die verspreiding van infeksie is ‘n belangrike deel van enige aansteeklike siekte, aangesien die dinamika van die siekte grootliks afhang van die tempo van oordrag van ‘n aansteeklike persoon na ‘n vatbare persoon. ‘n Oorsig is gedoen om te sien watter kompartementele epidemiologiese modelle alreeds bestaan. Ons het gevind dat baie van die manuskripte nie die nodige inligting voorsien wat nodig is om die resultate van die skrywers te repliseer nie, en slegs ‘n klein hoeveelheid van die modelle kon gesimuleer word. Die rede hiervoor is hoofsaaklik as gevolg van ‘n gebrek aan inligting of van foute in die artikel. Die modelle is in vier kategorieë vir die analise verdeel. Op grond van die TVI het ons tussen frekwensie- of digtheidsafhanklike oordrag onderskei, en as ‘n tweede kriterium het ons die modelle op die seksuele aktiwiteit van die vigs-groep onderskei. Daarna is die modelle binne en tussen die klasse vergelyk in terme van hul TVIs. Daar is gewys dat frekwensie-afhanklike oordrag gebruik moet word vir groter bevolkings. Dit is die geval van MIV, waar die siekte hoofsaaklik versprei word deur seksuele kontak. Die insluiting van die vigs-pasiënte in die groep van aansteeklike individue is belangrik vir die akkuraatheid van die oordrag-dinamika van MIV. Meer as helfte van die uitgesoekte studies aanvaar dat vigs-pasiënte te siek is om betrokke te raak by riskante seksuele gedrag. Ons sien dat die insluiting van vigs-pasiënte in die groep van aansteeklike individue ‘n beduidende uitwerking op die TVI het wanneer die waarde van die waarskynlikheid van oordrag van ‘n individu met vigs groter is as dié van die ander klasse. Die analise toon dat die TVI kan wissel afhangende van die parameter waardes en die aannames wat gemaak is. Baie modelle voeg verskeie parameter waardes bymekaar vir die waarskynlikheid van oordrag. Wanneer die parameter waardes nie apart gewys word nie, is dit moeilik om die werking van die TVI te verstaan, want daar is onbekende faktore wat ‘n invloed op die TVI het. Die verbetering van die akkuraatheid van die TVI kan ons help om die faktore wat dit beïnvloed beter te verstaan, en dit kan ook help om meer realistiese resultate te produseer. Om die waarskynlikheid van oordrag as ‘n funksie van die viruslading te skryf kan help om die TVI meer akkuraat te maak en dit kan ook help om die effek wat virale dinamika op die bevolkingsoordrag-dinamika het, beter te verstaan.

<p>The aim of this study was to assess the factors associated with HIV risk behaviours in women in Livingstone, Zambia. A cross-sectional analytical survey using a structured questionnaire was carried out in two sites in Livingstone, which were selected on the basis of differences in socio-economic status. Married women and women in the urban community are at high risk of contracting HIV and every effort should be made to ensure that HIV/AIDS programmes help to reduce their vulnerability to HIV infection.</p>

This epidemiological investigation focussed on <i>Campylobacter jejuni </i>and <i>Campylobacter coli</i> in the north east of Scotland (Grampian). Scotland, in 2007, had an annual incidence of 101.5 cases/100,000 people, while in Grampian this figure was 120/100,000.  <i>C. jejuni </i>and <i>C. coli </i>are ubiquitous and are natural commensals of a range of animals, therefore understanding the epidemiology of these organisms involves identifying their putative sources and monitoring their dynamics in such hosts.  In this study, the use of various epidemiological tools showed that humans are infected from different sources and notably by chicken. Between 2001 and 2006, the population structure of <i>Campylobacter </i>in retail chicken changed  more than in humans, as shown by characterisation by Multilocus sequence typing (MLST).  There was however a high degree of overlap between these respective strains suggesting that chickens are a major source of human infection.  Furthermore, comparison of the same strains using antimicrobial resistance profiles revealed the same commonality of strains. Infection in the high risk 0-4 year old age group was shown to be attributable mainly to chicken in an urban environment but more attributable to cattle in rural areas.  This may reflect relative rates of exposure to these important sources of <i>Campylobacter.</i> Characterisation of a large outbreak in north east Scotland using various typing techniques identified chicken liver paté as a vehicle for <i>C. jejuni </i>infection; multiple strains were identified in the food and more than one patient displayed co-infection with different strains. These investigations have provided useful information which contributes to the overall surveillance of human campylobacteriosis and the epidemiology of <i>Campylobacter </i>in different hosts.

Background: Group B streptococcus (GBS) is a leading cause of invasive bacterial disease in neonates. The possibility of maternal immunization with GBS-vaccines is being explored. Vaccine candidates include serotype-specific polysaccharide-protein conjugates and GBS surface proteins, including pilus island proteins. In this project, we aimed to undertake capsular serotype identification, pilus island identification and genotypic characterization of GBS isolates associated with colonization in mothernewborn dyads and invasive disease in infants. Methods: Colonizing GBS isolates were identified by vaginal swabbing of mothers (n=541) during active labor and from skin of their newborns post-delivery (n=395). Invasive GBS isolates from infants (n=284) were identified through laboratory-based surveillance. GBS serotyping was done by latex agglutination. Serologically nontypeable isolates were typed by a serotype-specific PCR method. The pilus islands from 541 colonizing isolates and 284 invasive isolates were characterized by real-time PCR targeting the ancillary protein 1 and 2. We undertook sequence typing based on the three most heterogeneous genes (adhP, atr and glnA) of multilocus sequence typing (MLST) on GBS isolates identified in young-infants with invasive disease (n=283) and those associated with maternal (n=525) and newborn colonization at birth (n=369). A total of 121 colonizing and 131 invasive disease GBS isolates that were representative of 55 and 35 clusters respectively were analyzed by the remaining four MLST genes. The gbs2018 locus was characterized by DNA sequencing.

A study to assess the potentials of some commensal bacteria that belong to Staphylococcus, Acinetobacter and Stenotrophomonas genera as reservoirs of antibiotic resistance determinants in the environment of Nkonkobe Municipality of the Eastern Cape Province, South Africa, was carried out using standard microbiological and molecular techniques. A total of 120 Staphylococcus isolates which consisted of Staphylococcus haemolyticus (30%), Staphylococcus aureus (23.3%) from pig; Staphylococcus capitis (15%) from goat; Staphylococcus heamolyticus (5%) and Staphylococcus xylosus (15%) from cattle and other Staphylococci (11%) from dead chicken and pigs were isolated. About 23.3% of these isolates were coagulase positive and 76.7% were coagulase negative. This difference in prevalence along coagulase production divide was statistically significant (p < 0.05). Eighty-six Acinetobacter species (Acinetobacter baumannii/calcoaceticus and Acinetobacter haemolyticus) were also isolated from Alice and Fort Beaufort towns samples, while 125 Stenotrophomonas maltophilia isolates were from grass root rhizosphere (96%) and soil butternut root rhizosphere (4%). Between 75-100% of the Staphylococccus species were resistant to Penicillin G, tetracycline, sulphamethaxole and nalidixic acid; about 38 % were methicillin resistant, consisting of 12.6% methicillin resistant Staphylococcus aureus (MRSA) from pig and a total of 12% vancomycin resistant were observed. Also, 12% of the isolates were erythromycin resistant while 40.2 % were resistant to the third generation cephalosporin, ceftazidime. The antibiotic resistance genes vanA, VanB, eryA, eryB, eryC were not detected in all the phenotypically resistant Staphylococccus species, but mec A gene and mph genes were detected. In the Acinetobacter species, a wide range of 30-100% resistance to penicillin G, ceftriazone, nitrofurantoin, erythromycin, and augmentin was observed. Polymerase chain reaction (PCR) revealed the presence of Tet(B) and Tet(39) genes in these species, while Tet (A), Tet(M) and Tet(H) were absent. Also, 9.3% of the Acinetobacter species showed phenotypic production of extended spectrum beta lactamases (ESBLs) while 3.5% were positive for the presence of blaCTX-M-1 genes. The Stenotrophomonas maltophilia isolates showed varying resistance to meropenem (8.9%), cefuroxime (95.6 %), ampicillin-sulbactam (53.9%), ceftazidime (10.7%), cefepime (29.3 %), minocycline (2.2%), kanamycin (56.9%), ofloxacin (2.9%), levofloxacin (1.3%), moxifloxacin (2.8%), ciprofloxacin (24.3%), gatifloxacin (1.3%), polymyxin B (2.9 %), cotrimoxazole (26.1%), trimethoprim (98.6%), aztreonam(58%) and Polymyxin B (2.9 %). The isolates exhibited significant susceptibility to the fluoroquinolones (74.3-94.7 %), polymycin (97.1%) and meropenem (88.1%). Only sul3 genes were the only sulphonamide resistance gene detected among the trimethoprim-sulphamethoxazole resistant isolates. The observed multiple antibiotic resistance indeces (MARI) of >2 for Staphylococcus species, Acinetobacter species and Stenotrophomonas maltophilia suggest that they have arisen from high-risk sources where antibiotics are in constant arbitrary use resulting in high selective pressure. The presence of tetracycline resistance genes in Acinetobacter species justifies the observed phenotypic resistance to oxytetracycline and intermediate resistance to minocycline. High phenotypic resistance and the presence of some resistance genes in Staphylococcus species is a possible threat to public health and suggests animals to be important reservoirs of antibiotic resistance determinants in the environment. Indiscriminate use of antibiotics induces this kind of antibiotic resistance and should be discouraged. Personal hygiene is encouraged as it reduces the load of Acinetobacter species contacted from the environment that may be difficult to control. Commensal Stenotrophomonas maltophilia are as important as their clinical counterparts due to their roles in opportunistic infection, antibiotic resistance and their associated genes, especially sul gene. Personal hygiene is hereby advocated especially when in contact with soil, plants and plants’ rhizospheric soil

This study investigated how gastrointestinal and skin bacterial infections were affected by differential expression of connexin (Cx) 26 and a disintegrin and metalloprotease (ADAM) 17 in vitro. Cx26 is a component of gap junctions, which facilitate the transfer of small molecules between two cells. Recessive mutations in Cx26 cause non syndromic hearing loss (NSHL), and in certain populations, specific mutations account for the majority of Cx26 related NSHL. Their common occurrence suggests that they may provide a heterozygous, protective advantage to carriers. In this study adherence by the attaching and effacing pathogen Enteropathogenic Escherichia coli (EPEC) was significantly reduced in cells expressing mutant Cx26 compared to wild type Cx26. Furthermore, EPEC adherence and invasion of an alternative enteric pathogen, Shigella flexneri were reduced following treatment with Cx26 short-interfering-RNA in intestinal cells. These findings suggest that the loss of functional Cx26 expression improves protection against enteric bacteria. ADAM17 releases substrates including tumour necrosis factor alpha and ligands of the epidermal growth factor receptor and therefore is involved in the induction of immune responses and maintenance of the epidermal barrier. This study demonstrated that ADAM17 provides protection during Staphylococcus aureus infection of keratinocytes. Subsequently the protective effects of ADAM17 mediated protection were explored. Secretion of the proinflammatory cytokines Interleukins 6 and 8 correlated with ADAM17 activity. Additionally gene expression profiling was performed which identified the IL-17 signalling pathway, which is known to be important during S. aureus infection, as a potential downstream target of ADAM17. In summary, based on these findings, Cx26 and ADAM17 may represent potential therapeutic targets for gastrointestinal and skin bacterial pathogens.

This research project investigated the impact of an action research intervention implemented to reducing surgical wound infection in one of the acute care hospitals in India. The study aimed to develop and implement a clinical practice improvement program in reducing surgical wound infection by improving the hand washing and wound dressing practices of nurses. The study also aimed to identify the important contributing factors to a model that predicts surgical wound infection. Pre-post evaluation measures were taken to compare the results of surgical wound infection rate before and after the implementation of the intervention. Surgical wounds of two thousand patients (one thousand before the intervention and another one thousand after) were assessed to determine the wound infection rate and severity of wound infection. The hand washing and wound dressing practices of forty nurses were observed. These same nurses were involved in the intervention using a participatory action research process. The results of the study suggest that there was a marked, significant reduction in the rate and severity of wound infection following the implementation of the intervention. By increasing the hand washing facilities in the ward, educating nurses on the importance of better hygiene, pre-operative shaving and post-operative wound care, the hand washing and wound dressing practices of nurses improved considerably. These improvements resulted in a reduction in the number and severity of patients' surgical wound infections. The study also examined the contribution of different factors to surgical wound infection in a Indian hospital. Significant predictive factors were the patients' age, longer pre-operative hospital stay, extended pre-operative shaving time before surgery, wound class, and co-morbidity of the patient. The identification of risk factors that contributed to increased surgical wound infection for example pre-operative skin preparation, pre-operative hospital stay of the patient would help in taking appropriate measures at the ward level and organisation as a whole. Nosocomial infections extends to an unnecessary lengthy hospital stay, additional treatment increased mortality and morbidity, and increased cost to the patients and the nation as a whole. This project proved that educational mentoring, data surveillance processes and involving the nurses in an action research process were effective in enabling participants to improve their clinical practice and thereby reduce the incidence of patients' surgical wound infections. Establishing infection control teams, ongoing surveillance and feedback to staff of nosocomial infection rates is an urgent need in all Indian hospitals. Organisational management, as a priority, need to provide funding and staff dedicated to undertaking this essential work. Health care professionals can no longer plead ignorance of a situation for which all have a moral and professional responsibility.

Amendments appended. / Bibliography: leaves 140-165. / xi, 165 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 2005

Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliography.

Dissertation--Leiden--Universität, 2005. / Résumé en néerlandais. Bibliogr. p. 145-146.