Review article
Pathogenesis of tuberculosis: pathway to apical localization

https://doi.org/10.1016/0962-8479(94)90002-7Get rights and content

Abstract

We have examined the published work of investigators which dealt with the pathogenesis of tuberculosis, especially the following: the infective dose, the yield of bacilli from the primary lesion and primary complex, the predominant location of the minimal lesion, the hypotheses of a vulnerable region in the lung and the specific pathways (endogenous or exogenous) by which tubercle bacilli cause disease. More knowledge of the pathogenic pathway to tuberculosis would provide clues to the development of new vaccines and drug regimens that can intervene at a specific stage in the pathogenesis.

Based on the examination of the literature on pathogenesis of human tuberculosis and our findings in a guinea-pig model of experimental airborne tuberculosis, we have proposed an hypothesis which integrates the endogenous and exogenous pathways to tuberculosis. This hypothesis is based on the following observations:

  • 1.

    1. The infectious dose is very low, usually 1–5 tubercle bacilli.

  • 2.

    2. The first implant can occur anywhere in the lungs.

  • 3.

    3. The cavitary lesion, characteristic of tuberculous disease, is often located in the apical regions in the lungs.

  • 4.

    4. Whereas the primary implant can occur anywhere in the lungs, for the progression from infection to disease, the tubercle bacilli must gain access to the “vulnerable” regions in the apex of the lungs.

Our hypothesis states that in areas of the world where there is a low risk of infection with tubercle bacilli low incidence of vaccination or sensitization to environmental mycobacteria, or high incidence of high virulent isolates, the virulent tubercle bacilli reach the vulnerable region via a bacillemia during the first infection. In areas of the world where there is a high risk of infection with tubercle bacilli, high incidence of vaccination or sensitization to environmental mycobacteria or a high incidence of low virulent isolates, the tubercle bacilli reach the vulnerable region via the airway, which requires repeated episodes of infection as the probability of a first implant occurring in the vulnerable regions is low.

Résumé

Les publications des travaux des chercheurs portant sur la pathogénie de la tuberculose ont été examinées, en particulier sur les sujets suivants: dose infectante, production de bacilles en provenance de la lésion et du complexe primaires, localisation la plus commune de la lésion minime, hypothèses d'une région vulnérable dans le poumon et cheminements spécifiques (endogènes ou exogènes) par lesquels le bacille tuberculeux peut causer la maladie. Des connaissances plus approfondies sur le cheminement pathogène de la tuberculose procureraient des indices propices au développement de nouveaux vaccins et de régimes de traitement susceptibles d'intervenir dans la pathogénie à un stade spécifique.

A partir d'un examen de la littérature sur la pathogénie de la tuberculose humaine et de nos observations dans un modèle cobaye d'une tuberculose aérogène expérimentale, nous proposons une hypothèse qui intègre les voies endogènes et exogènes préludant à la tuberculose. Cette hypothèse est basée sur les observations suivantes:

  • 1.

    1. La dose infectante est très basse, normalement de 1 à 5 bacilles tuberculeux.

  • 2.

    2. La première implantation peut survenir sur n'importe quel territoire du poumon.

  • 3.

    3. La lésion cavitaire, caractéristique de la maladie tuberculeuse, siège souvent dans les régions apicales des poumons.

  • 4.

    4. Tandis que l'implantation primitive peut survenir dans n'importe quelle partie du poumon, le bacille tuberculeux doit accéder aux régions ‘vulnérables’ dans l'apex du poumon.

Notre hypothèse suggère que dans les régions du monde où existent un faible risque d'infection par le bacille tuberculeux, une faible incidence de vaccination ou de sensibilisation aux mycobactéries environnementales, ou une incidence élevée d'isolayts hautement virulents, les bacilles tuberculeux virulents atteignent la région vulnérable via une bacillémie au cours de l'infection initiale. Dans les régions du monde comportant un risque élevé d'infection par le bacille tuberculeux, une incidence élevée de vaccination ou de sensibilisation aux mycobactéries environnementales, ou une incidence élevée d'isolats de faible virulence, les bacilles tuberculeux atteignent la région vulnérable via les voies aériennes, ce qui requiert des épisodes répétés d'infection en raison de la faible probabilité de la survenue d'une implantation dans les régions vulnérables par première intention.

Resumen

Examinamos las publicaciones de trabajos de investigación con respecto a la patogénesis de la tuberculosis, especialmente sobre los aspectos siguientes: dosis infectante, producción de bacilos provenientes de la lesión primaria y del complejo primario, la localización predominante de la lesión mínima, las hipótesis sobre una región vulnerable en el pulmón y las vías específicas (endógenas o exógenas) por las cuales el bacilo causa la enfermedad. Un mayor conocimiento sobre la patogenia de la tuberculosis podría procurar índices propicios para el desarrollo de nuevas vacunas y de esquemas terapéuticos que podrían intervenir en un estadio específico de la patogénesis.

En base a un examen de la literatura sobre la patogénesis de la tuberculosis humana y a nuestros hallazgos en un modelo experimental de tuberculosis aerógena en cobayo, hemos propuesto una hipótesis que integra las vías endógenas y exógenas que conducen a la tuberculosis. Esta hipótesis se basa en las observaciones siguientes:

  • 1.

    1. La dosis infectante es muy baja, normalmente de 1 a 5 bacilos tuberculosos.

  • 2.

    2. La primera implantación puede ocurrir en cualquier región del pulmón.

  • 3.

    3. La lesión cavitaria, característica de la enfermedad tuberculosa, se localiza con frecuencia en las regiones apicales del pulmón.

  • 4.

    4. Aunque la implantación primaria puede ocurrir en cualquier región del pulmón, en su progreso de la infección a la enfermedad el bacilo tuberculoso debe acceder a las regiones ‘vulnerables’ en el ápice del pulmón.

Nuestra hipótesis propone que en las áreas del mundo donde existe un riesgo de infección bajo para el bacilo tuberculoso, una baja incidencia de vacunación o de sensibilización a las micobacterias ambientales o una incidencia elevada de aislados altamente virulentos, los bacilos tuberculosos virulentos alcanzan la región vulnerable vía una bacilemia durante la infección inicial. En las áreas del mundo con riesgo elevado de infección por el bacilo tuberculoso, con alta incidencia de vacunación o de sensibilización a micobacterias ambientales o una alta incidencia de aislados de escasa virulencia, los bacilos tuberculosos alcanzan la región vulnerable por vía aérea, lo cual requiere episodios repetidos de infección, ya que la probabilidad de una primera implantación en las regiones vulnerables es baja.

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