Thesis (M.S.)--University of Wyoming, 2008. / Title from PDF title page (viewed on August 4, 2009). Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 117-140). Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 117-140). Also available online.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 108-151). Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2006. / Also available online.

Thesis (Ph.D.)(Zoology)--University of Pretoria, 2007. / Includes summary. Includes bibliographical references. Available on the Internet via the World Wide Web.

Human rabies is a zoonotic viral disease that affects thousands of people worldwide, especially in the developing countries of Africa and Asia. There are two distinct biotypes of lyssavirus genotype 1 circulating in South Africa: a canine biotype circulating in domestic dogs, bat-eared foxes and black-backed jackals and a mongoose biotype circulating in herpestids. The presence of LBV, MOKV and DUVV has been demonstrated in South African animal species, but apart from two documented cases of Duvenhage infection in humans, no other lyssaviruses other than genotype 1 have been reported to clinically manifest in humans. Since canine rabies is endemic to the KwaZulu Natal province where the majority of human rabies cases occur, dog vaccination campaigns have been implemented to control and prevent rabies in the region. The first outbreak of canine rabies in the province from the 1950s to 1968 was successfully controlled, but after its re-emergence in the 1970s dog vaccination campaigns have been unsuccessful for a variety of reasons, including lack of commitment for implementation of effective control measures and the difficulty of accessing certain areas in the province. In addition to these problems, human rabies emerged in the Limpopo province during 2005/2006. This emergence was potentially due to the introduction of canine rabies from either black-backed jackals or dogs in Zimbabwe, as there was a large increase of canine rabies cases in the province before the human outbreak. Some dog vaccination campaigns and stray dog population control measures were established in the province, but there are still human rabies cases being reported from the region annually. In order to gain a clearer understanding of human rabies in the country, this study was undertaken to elucidate various epidemiological aspects of human rabies in the country, to correlate the existing knowledge of animal rabies cycles to human rabies cycles and also to determine whether or not lyssaviruses other than genotype 1 have been involved in causing human rabies in South Africa. The study confirmed that the domestic dog is the primary vector for human rabies in South Africa, with most cases occurring in the KwaZulu Natal province. Men and young adults under the age of 21 were most affected. Only very small portion of affected people sought and received post-exposure prophylaxis. This was either due to a lack of vaccine and immunoglobulin or a lack of knowledge of the risk of the disease after an animal exposure. The findings from the molecular epidemiology study reinforced the previous findings which correlate most human rabies cases with the coastal KwaZulu Natal canine cluster identified in previous studies. As humans are a dead end host to rabies infection, it was expected that the molecular epidemiology of the human rabies isolates would mimic the molecular epidemiology of the existing animal cycles and this proved to be the case. The human rabies virus isolates all grouped closely to their representative animal cycles, which grouped by respective geographical location. The study also reinforced findings of the establishment of a new Free State canine rabies cycle, originating from the coastal KwaZulu Natal canine rabies cluster. The primary laboratory confirmation test of rabies is the fluorescent antibody test which does not distinguish between genotypes or the two biotypes circulating in South Africa. The study was undertaken, in part, to elucidate the various genotypes and biotypes responsible for human rabies in South Africa, as there is a large diversity of lyssaviruses in South Africa, evidenced by the fact that the first ever reported human rabies case in South Africa was due to a mongoose exposure. Molecular epidemiology is a subfield of epidemiology and thus can be used to reach epidemiological conclusions. No lyssavirus genotypes other than genotype 1 were implicated in the human rabies cases, indicating that the African rabies-related lyssavirus exposures are uncommon and while exposures can happen (as shown in 2006), they are not likely to be of significant public health concern and the focus should be on genotype 1. The findings of the study emphasize the importance of rabies as a zoonotic disease of humans in South Africa, which despite having severe health impact on the local human populations is still greatly underestimated. Moreover, the study summarizes epidemiological data of known human rabies cases for a period of 1983 to 2007 and thereby provides a useful and comprehensive report on the status of the disease in South Africa for last 25 years. The database of human rabies cases established during this study can then assist in the future planning and prioritizing of rabies control and prevention efforts in the country. Copyright / Dissertation (MSc)--University of Pretoria, 2010. / Microbiology and Plant Pathology / unrestricted

Objectives: The hypothesis that BRO-1 selectively replaced the BRO-2 isoform of the Moraxella catarrhalis BRO β-lactamase was tested by examining the temporal distribution, antibiotic resistance and epidemiological characteristics of isolates from a long-term collection at a single locale. Methods: A rapid, one-step PCR assay conducted on 354 isolates spanning 1984-1994 distinguished bro alleles in over 97% of the β-lactamase-producing isolates. Probes of dot blots were used to distinguish PCR failure from non-β-lactamase-mediated penicillin resistance. Results: BRO-2 isolates comprised 0-10% of the population per year with no evidence of a decline overtime. All β-lactamase producers exceeded the clinical threshold for penicillin resistance. Bimodality of penicillin MICs for β-lactamase producers was caused by variation within BRO-1 rather than differences between BRO-1 and BRO-2. Non-β-lactamase factors also confer resistance to penicillin and may contribute to the BRO-1 bimodality. The 13 BRO-2 isolates were associated with diverse genotypes within which there was evidence of epidemiologically linked clusters. The exclusive association of BRO-2 with four unrelated genotypes suggested maintenance of BRO-2 by recurrent mutation or horizontal exchange. Conclusions: The relative rarity of BRO-2 throughout the study, the absence of a declining temporal trend, and genetic diversity within BRO-2 all failed to support the hypothesis that BRO-2 was more common in the past and has been selectively replaced by BRO-1.

The domestic dog is the principal reservoir of rabies in Nigeria and the source of infection for over 99% of human cases that have been documented. The first recorded cases of human and dog rabies were in 1912 and 1928 respectively. The disease has been continually diagnosed in the domestic dog until to date. One of the control measures practiced in this West African country includes the vaccination of domestic dogs with readily available rabies vaccines. However, trend analyses show that dog rabies is increasing probably indicating that the vaccination programmes are inadequate. Rabies is a member of the Lyssavirus genus and currently comprises of seven genotypes (GT 1-7) namely the classical rabies virus (RABV) GT1, Lagos bat virus (LBV) GT2, Mokola virus (MOKV) GT3, Duvenhage (DUVV) GT4, European bat lyssavirus type-1 (EBLV-1) GT5, European bat lyssavirus type-2 (EBLV-2) GT6 and Australian bat lyssavirus (ABL) GT7. Three of these have been identified in Nigeria (classical rabies (RABV) (GT 1), Lagos bat virus (LBV) (GT 2) and Mokola virus (MOKV) (GT 3). The domestic dog is the major maintenance and vector species of rabies in this country and the West Africa sub-region. This study was therefore undertaken to further elucidate the epidemiology of dog rabies in Nigeria. Secondly, it was the aim of this study to determine the phylogenetic relationships of dog rabies viruses and the distribution of the respective rabies variants. Finally, to assess the phylogenetic relationships of the viruses in the study sample with those of the neighbouring countries (Chad, Cameroon, Benin and Niger). A panel of 100 viruses recovered primarily from the domestic dog was included in the study. Partial regions of the nucleoprotein gene (n=100) and the cytoplasmic domain of the glycoprotein and the G-L intergenic region (n=80) were successfully amplified, sequenced and phylogenetically analysed. Nucleotide sequences of representative rabies viruses of the partial N gene of the neighbouring countries and elsewhere in Africa available in the GenBank were also included in the phylogenetic analysis. The phylogenetic analysis demonstrated that the rabies viruses from the study sample were closely related with a 99% sequence homology for both the N and G regions but despite the close homogeneity the viruses segregated into two major clusters. Within the major cluster 1, three sub-clades were identified comprising of rabies isolates from the northern part of Nigeria whereas cluster 2 was made of viruses from the southern part of the country together with an isolate from a stray dog. Further analysis of representative viruses from the study sample with viruses from the GenBank revealed an evolutionary link with the viruses from Chad, Benin, Cameroon and Niger with a ≥96% sequence homology. The demonstration of the evolutionary link of rabies viruses in the study sample and those from neighbouring countries indicates the transboundary nature of rabies and the existence of an active rabies cycle in the region. The study data revealed that a single major virus variant is circulating in domestic dogs in Nigeria belonging to the Africa 2 dog lineage. These data suggest that control strategies including mass vaccination with effective coverage of ≥70% and the control of stray dogs will contribute to the breaking of the rabies cycle. This will dramatically reduce the demand for post-exposure prophylaxis which is costly and not readily available in most states of the country. There is also a need to enforce strict movement of animals across international borders so as to diminish the spread of the infection from one area to another, as rabies still inflicts a considerable public health burden in the region and many parts of Africa. / Dissertation (MSc)--University of Pretoria, 2009. / Veterinary Tropical Diseases / unrestricted

The use of genomic information has gained increasing relevance in epidemiology and public health, particularly the inference of genetic networks of highly evolving pathogens like HIV. This approach offers objective evidence that allows for tracking transmission dynamics, and guiding intervention. However, the virus's high genetic diversity, combined with variations in risk factors and transmission rates among affected populations, leads to substantial differences in epidemic dynamics across different epidemiological contexts. Additionally, transmission networks inferred using a distance threshold often create many spurious edges among closely related sequences, resulting in abiological transmission cycles. Management of these networks as new sequences are generated also fuel a desire to track cluster growth over time. It is therefore advisable to develop molecular analysis tools that better capture the unique landscape of each epidemic, providing a portrayal that more closely mirrors the real epidemic scenario. This dissertation introduces novel tools aimed at optimizing genetic network analysis for epidemiological purposes, with a focus on HIV-1 but with stated potential further application in other pathogens. Due to their greater convenience compared to phylogenetic methods, the inference of transmission networks through genetic distance methods has been widely used for near-real-time surveillance of HIV-1. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV \textit{pol} gene sequence. In Chapter 2, Weaver \textit{et al.} introduces AUTO-TUNE, a heuristic scoring method to adaptively tune the distance threshold, to prevent giant cluster formation and maximize cluster numbers. This method was applied to various outbreaks, considering regional or temporal differences, to identify clusters with specific risk factors. For instance, we found the 0.015 threshold suits US-like epidemics, but a lower threshold of 0.005 better captures outbreaks like the CRF07 BC subtype among MSM in China. Conversely, a larger threshold is needed for regions where diverse risk factors and sparse sampling occur over longer periods. This adaptive approach aids public health officials in making more informed interventions. Genetic distance and phylogenetic tools often yield densely connected clusters, with many spurious edges that create unrealistic cycles, overestimating connectivity and inflating node degrees. In Chapter 4, we present a scalable approach, Conditionally Orthogonal Vertices For Edge Filtering in Epidemics (COVFEFE), to prune spurious edges through a straightforward application of the PC (unroll) algorithm originally developed for Bayesian graphical models. COVFEFE removes edges likely to be indirect, preserving cluster membership. It eliminates 29\%–80\% of spurious edges in simulated transmission chains with low intra-host mutation rates and 4\%–39\% in real HIV-1 epidemic data, often simplifying dense clusters to chains. Filtered networks align better with theoretical models, affecting analysis and modeling methods that use node or edge properties. COVFEFE is part of the HIV-TRACE molecular network inference package. The heterogeneity in risk factors and characteristics of the HIV-1 epidemic worldwide demands adapting bioinformatics tools for different contexts to meet local needs. In Chapter 4, we present HIV-TRACE GO, an extension of the HIV-TRACE software designed to enhance global HIV molecular epidemiology surveillance. This web application, developed primarily in JavaScript, enables real-time molecular surveillance with features tailored for multi-jurisdictional data management and internationalization. HIV-TRACE GO has been successfully implemented at CIENI-INER, a WHO-accredited HIV-1 sequencing reference laboratory in Mexico, demonstrating its feasibility for both local and international applications. We discuss the software architecture, key customizations, and its potential impact on public health surveillance. / Biology