Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

In paleopathology, the assessment of disease occurs through macroscopic observation, which is dependent on the preservation of the sample and the experience of the observer. Many disease events do not leave any visible signatures and therefore go undetected. The relatively new field of paleomicrobiology incorporates molecular techniques where microbial DNA, if present, is amplified from an archaeological sample. The identification of genetic material from micro-organisms, including bacteria and viruses, can confirm a diagnosis that was originally based on visible osteological or mummified tissue changes. Even more promising is the capability of molecular technology to detect microbial DNA evidence of disease processes that were not visibly evident.<p> Based on phylogenetic analyses of modern isolates, scientists have concluded that micro-organisms such as <i>Mycobacterium tuberculosis</i> and <i>Helicobacter pylori</i> have been associated with humans for thousands of years. <i>M. tuberculosis</i> is the causative agent of the disease tuberculosis, and <i>H. pylori</i> is known for its role in gastritis and peptic ulcers. Both are pathogenic bacteria that still impact the health of modern populations. Through the analysis of microbial DNA from these two bacteria in skeletal and mummified tissue, data can be accumulated regarding the spatial and temporal impact of these infections. Interestingly, due to the lengthy association between these bacteria and humans, phylogenetic studies on modern strains have shown that strain characterizations of both <i>M. tuberculosis</i> and <i>H. pylori</i> bacteria reveal connections with past human migrations.<p> In 1999, human remains were discovered eroding out of a glacier in northern British Columbia, Canada on the traditional territory of the Champagne and Aishihik First Nations. The Aboriginal elders named the site Kwäday Dän Tsìnchi, which means long ago person found. Radiocarbon testing of bone collagen and artifacts from the site suggested a time-frame of approximately AD 1670 to 1850, which is either pre-European contact or early post-contact for that area. I analyzed the tissues of the ancient individual specifically for genetic evidence of <i>M. tuberculosis</i> and <i>H. pylori</i> to identify partial health status and determine if a connection could be made to strains associated with European populations to clarify whether the site was pre or post-European contact.<p> Through polymerase chain reaction (PCR) testing of the individuals tissues with primers specific for the IS<i>6100</i> insertion sequence, <i>TbD1</i>, and <i>Rv3479</i>, <i>katG</i> and <i>gyrB</i> genes, I identified evidence of a possible latent tuberculosis infection. Genetic characterization of the <i>katG</i> gene associated with the ancient <i>M. tuberculosis</i> strain revealed a potential connection with European strains. Amplification and sequencing of the <i>gyrB</i> gene fragment indicated the presence of two alleles that may have been the result of a selective pressure.<p> PCR testing of the individuals stomach tissue with specific primers for regions with the <i>vacA</i> gene resulted in a positive identification of <i>H. pylori</i> DNA. Genetic characterization of this virulence-associated gene indicated that the strain contained a <i>vacA</i> signal (s) region s2 allele. This allele is more commonly identified in Western strains that do not cause disease, which suggests that the individual had no gastric symptoms and that European strains were present in northwestern Canada at that time. The vacA middle (m) region contained a hybrid m2a/m1d sequence. Modern hybrids are rare but they have been identified in Asian strains. Studies have shown that the m2a allele is more common in Western strains. A phylogenetic analysis identified that the m1d region clusters with previously published novel strains associated with Aboriginal individuals that are closely related to Asian strains. This indicates a past connection between the ancient individual and his ancestors who arrived in the New World from Asia thousands of years ago.

In paleopathology, the assessment of disease occurs through macroscopic observation, which is dependent on the preservation of the sample and the experience of the observer. Many disease events do not leave any visible signatures and therefore go undetected. The relatively new field of paleomicrobiology incorporates molecular techniques where microbial DNA, if present, is amplified from an archaeological sample. The identification of genetic material from micro-organisms, including bacteria and viruses, can confirm a diagnosis that was originally based on visible osteological or mummified tissue changes. Even more promising is the capability of molecular technology to detect microbial DNA evidence of disease processes that were not visibly evident.<p> Based on phylogenetic analyses of modern isolates, scientists have concluded that micro-organisms such as <i>Mycobacterium tuberculosis</i> and <i>Helicobacter pylori</i> have been associated with humans for thousands of years. <i>M. tuberculosis</i> is the causative agent of the disease tuberculosis, and <i>H. pylori</i> is known for its role in gastritis and peptic ulcers. Both are pathogenic bacteria that still impact the health of modern populations. Through the analysis of microbial DNA from these two bacteria in skeletal and mummified tissue, data can be accumulated regarding the spatial and temporal impact of these infections. Interestingly, due to the lengthy association between these bacteria and humans, phylogenetic studies on modern strains have shown that strain characterizations of both <i>M. tuberculosis</i> and <i>H. pylori</i> bacteria reveal connections with past human migrations.<p> In 1999, human remains were discovered eroding out of a glacier in northern British Columbia, Canada on the traditional territory of the Champagne and Aishihik First Nations. The Aboriginal elders named the site Kwäday Dän Tsìnchi, which means long ago person found. Radiocarbon testing of bone collagen and artifacts from the site suggested a time-frame of approximately AD 1670 to 1850, which is either pre-European contact or early post-contact for that area. I analyzed the tissues of the ancient individual specifically for genetic evidence of <i>M. tuberculosis</i> and <i>H. pylori</i> to identify partial health status and determine if a connection could be made to strains associated with European populations to clarify whether the site was pre or post-European contact.<p> Through polymerase chain reaction (PCR) testing of the individuals tissues with primers specific for the IS<i>6100</i> insertion sequence, <i>TbD1</i>, and <i>Rv3479</i>, <i>katG</i> and <i>gyrB</i> genes, I identified evidence of a possible latent tuberculosis infection. Genetic characterization of the <i>katG</i> gene associated with the ancient <i>M. tuberculosis</i> strain revealed a potential connection with European strains. Amplification and sequencing of the <i>gyrB</i> gene fragment indicated the presence of two alleles that may have been the result of a selective pressure.<p> PCR testing of the individuals stomach tissue with specific primers for regions with the <i>vacA</i> gene resulted in a positive identification of <i>H. pylori</i> DNA. Genetic characterization of this virulence-associated gene indicated that the strain contained a <i>vacA</i> signal (s) region s2 allele. This allele is more commonly identified in Western strains that do not cause disease, which suggests that the individual had no gastric symptoms and that European strains were present in northwestern Canada at that time. The vacA middle (m) region contained a hybrid m2a/m1d sequence. Modern hybrids are rare but they have been identified in Asian strains. Studies have shown that the m2a allele is more common in Western strains. A phylogenetic analysis identified that the m1d region clusters with previously published novel strains associated with Aboriginal individuals that are closely related to Asian strains. This indicates a past connection between the ancient individual and his ancestors who arrived in the New World from Asia thousands of years ago.

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Helicobacter pylori infection causes chronic type B gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tumor. Infection with H. pylori is common in parts of the developing world. The Clínica Misional Nuestra Señora de Guadalupe serves indigenous people of the Ecuadorian Amazon. At the clinic, gastritis is a common diagnosis that is based solely on reported symptoms and is presumed to be due to H. pylori infection. Additionally, gastric cancer, a corollary of H. pylori infection, is the leading cause of cancer deaths in Ecuador and, thus, an important public health concern. To the best of our knowledge, the prevalence of H. pylori infection among the inhabitants of rural Ecuador has never been assessed. The primary aim of this study was to determine the seroprevalence of H. pylori in this population. We compared rates of seropositivity among patients with and without symptoms suggestive of gastritis and among patients who reported untreated and exclusively treated water consumption. Additionally, a sampling of children was tested to begin to assess the age of serological conversion. Using the Quidel QuickVue H. pylori gII test, we found near universal seropositivity among adults aged 18 to 65 years (117/120 = 98%) and among children aged 2 to 18 years (13/14 = 93%). Given the high prevalence of H. pylori and its complications in rural Ecuador, this population may benefit from intervention to eradicate the bacterium. However, there is a lack of evidence to inform management decisions. There is a need for studies with large numbers of patients and long-term follow-up to assess the costs and benefits of population-based treatment.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 165-168). Also available online.