Molecular epidemiology of human rabies diagnosed in South Africa between 1983 and 2007

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. CopyrightDissertation (MSc)--University of Pretoria, 2010.Microbiology and Plant Pathologyunrestricte

Investigation of the intra-cellular localisation of Retinoblastoma Binding Protein 6 using immunofluorescence microscopy

Philosophiae Doctor - PhD (Biochemistry)Human Retinoblastoma Binding Protein 6 (RBBP6) is a 200 kDa protein that has been implicated in a number of crucial cellular processes. It forms part of the mRNA 3'-end processing complex in both humans and yeast, and it contains an RS-like domain and interacts with core splicing proteins, suggesting multiple roles in mRNA processing. Through its RING finger domain it has been implicated in catalysing ubiquitination of the tumour suppressor p53, the oncogene Y-Box Binding Protein 1 (YB-1) and the DNA replication-associated protein zBTB38. It is one of only a few proteins known to bind to both p53 and pRb. At the N-terminus of the protein is the DWNN domain, an ubiquitin-like domain which is found only in this protein family. Four protein isoforms of RBBP6 have been identified in humans, all of which contain the DWNN domain: isoform 1 contains 1972 residues, isoform 2 contains 1758 residues and isoform 4 contains 952 residues. Isoform 3, which contains the first 101 residues of the full length protein (isoform 1), including the DWNN domain, followed by an unique 17-amino acid tail, is reported to be expressed independently of the other isoforms and to be down-regulated in a number of cancers

Epidemiology of human rabies in South Africa, 1983-2007

Rabies remains a global public health problem but increasingly so in the developing world. Given a lack of awareness, priority and diagnostic capability, very few developing countries, especially in Africa, report on laboratory confirmed human rabies cases. Here we present a retrospective study on the epidemiology of human rabies in Republic of South Africa for a 25-year period, 1983-2007, based on laboratory confirmed cases. The study highlights the role of the domestic dog as a reservoir and vector of rabies and contrasts rabies endemic areas. From the collective data set, epidemiological aspects that include various features of these human rabies cases as well as failures in or towards the treatment of exposures are reported. Molecular analysis of virus isolates did not identify any additional cases of rabies attributed to infection with the Duvenhage, Lagos bat or Mokola or any other rabies-related viruses.The Poliomyelitis Research Fund (Grant no. 07/11) and A.S.P. was supported by a National Research Foundation bursary.http://www.elsevier.com/locate/virusresnf201