Human tuberculosis - an ancient disease, as elucidated by ancient microbial biomolecules

Tuberculosis is a major cause of death but infected people with effective immunity may remain healthy for years, suggesting long-term coexistence of host and pathogen. Direct detection and characterisation of ancient microbial DNA and lipid biomarkers confirms palaeopathological diagnoses. Archaeological Mycobacterium tuberculosis resembles extant lineages indicating the timescale for evolutionary changes is considerably longer than originally believed. (C) 2009 Elsevier Masson SAS. All rights reserved

Intestinal tuberculosis

Purpose of reviewIntestinal tuberculosis (TB) is increasing due partly to the HIV pandemic. Its clinical presentation mimics inflammatory conditions such as Crohn's disease and malignancies, which are becoming more prevalent, so the diagnosis is problematic.Recent findingsGreater awareness of intestinal TB is needed, both in countries where TB is endemic and developed countries with immigrant populations. Some strains of Mycobacterium tuberculosis are associated with more extrapulmonary disease and greater dissemination, thereby exacerbating the rise in HIV-associated extrathoracic TB. Recent retrospective and prospective studies are leading to the development of diagnostic algorithms. A wide range of imaging techniques is available for sampling and diagnosis. New biochemical, immunological and molecular diagnostic methods are being developed but must be standardized and validated. Developments in drug delivery will facilitate oral therapy even in patients suffering from malabsorption.SummaryThere is an increasing consensus on the risk factors and clinical presentations of intestinal TB. Imaging techniques, coupled with fine needle biopsies, are useful aids to diagnosis, but most important is a greater awareness of the condition by clinicians

Pathogenic microbial ancient DNA: a problem or an opportunity?

Copyright © Royal Society 2006Eske Willerslev, Alan Coope

Insights gained from palaeomicrobiology into ancient and modern tuberculosis

The direct detection of ancient Mycobacterium tuberculosis molecular biomarkers has profoundly changed our understanding of the disease in ancient and historical times. Initially, diagnosis was based on visual changes to skeletal human remains, supplemented by radiological examination. The introduction of biomolecular methods has enabled the specific identification of tuberculosis in human tissues, and has expanded our knowledge of the palaeopathological changes associated with the disease. We now realize that the incidence of past tuberculosis was greater than previously estimated, as M. tuberculosis biomarkers can be found in calcified and non-calcified tissues with non-specific or no visible pathological changes. Modern concepts of the origin and evolution of M. tuberculosis are informed by the detection of lineages of known location and date

Insights gained from ancient biomolecules into past and present tuberculosis-a personal perspective.

Ancient and historical tuberculosis (TB) can be recognized by its typical paleopathology in human remains. Using paleomicrobiology, it is possible to detect many more individuals infected with TB but with no visible lesions. Due to advances in molecular analysis over the past two decades, it is clear that TB was widespread in humans from the Neolithic period and has remained so until the present day. Past human populations were associated with different lineages of the Mycobacterium tuberculosis complex, thereby elucidating early human migrations. Using paleomicrobiology, it is possible to detect individuals infected with TB who are also co-infected with other bacteria or parasites. TB is also found in hosts with co-morbidities such as neoplasms, or metabolic disorders such as rickets and scurvy. In well-preserved human skeletal or mummified tissue, whole genome sequencing has detected individuals with multiple infections of different M. tuberculosis strains. Such studies put modern findings into context and emphasize the importance of human population density in such circumstances

Can the colonisastion resistance of the oral microflora be enhanced?

Colonisation resistance arises from the integrastion and synergy of a microbial flora, which thereby excludes extraneous potential colonisers. The factors influencing colonisation resistance in the oral cavity are considered and specific examples of actual or potential clinical applications are discussed. these are based on pre-emptive colonisation or competitive displacement

In situ PCR for Mycobacterium tuberculosis in endoscopic mucosal biopsy specimens of intestinal tuberculosis and Crohn disease

Tuberculosis and Crohn disease are granulomatous disorders affecting the intestinal tract with similar clinical manifestations and pathologic features. We evaluated the use of in situ polymerase chain reaction (PCR) using Mycobacterium tuberculosis complex-specific primers for IS61 10 to differentiate these 2 disorders in archival mucosal biopsy specimens. In situ PCR was positive in 6 of 20 tuberculosis biopsy specimens and I of 20 Crohn disease biopsy specimens. Staining was localized to a site of granulomatous inflammation in 3 of the tuberculosis specimens and in the Crohn, disease specimen. In the other tuberculosis biopsy specimens, positive staining was localized to inflammatory granulation tissue and to a focus of intact mucosa without granulomatous inflammation. The presence of M tuberculosis DNA in Crohn disease could be due to coexisting latent tuberculosis or indicate a role for these bacteria in triggering an abnormal immune response. Therefore, in situ PCR is potentially useful to differentiate intestinal tuberculosis from Crohn disease, if the sensitivity is improved

Accumulation of streptococci on teeth in a laboratory microcosm (artificial mouth)

The accumulation on teeth of three strains of oral bacteria, ‘Streptococcus mitior’ LPA-1, Streptococcus mutans C67-1, and Streptococcus rattus BHT, was studied from 8 to 90 hours after inoculation. Direct and viable counts demonstrated that strains BHT and C67-1 accumulated more rapidly than strain LPA-1, with fastest growth during the first 16 hours (td8-16h 3.6-4.8 h). In older cultures, S. mutans and S. rattus continued to accumulate and a high proportion of the cells were viable. In contrast, ‘S. mitior’ cultures contained many non-viable organisms, possibly due to hydrogen peroxideinduced death. When S. rattus was co-cultured with ‘S. mitior’ it was strongly inhibited during the first 24 hours, but increased in proportion after 66 and 90 hours. It was concluded that in the interaction between ‘S. mitior’ and S. rattus during initial plaque development, a potentially rapid initial growth rate was of less importance than the ability to antagonise the other organism