Human Host Factors Which Affect Vulnerability to Tuberculosis Infection

Human Host Factors Which Affect Vulnerability to Tuberculosis Infection - Once the TB bacillus finds an entry into the human lung, its interaction with the host immune system and the impact of the host’s other comorbid medical conditions ultimately determines whether infection is established and whether it progresses to clinical disease. Substantial immunological research has begun to elucidate key steps in the human immune system’s attempt to contain and eliminate TB. Simply stated, once MTB breaches the structural defences of the upper airways and reaches the distal lung, innate mechanismsinvolving macrophages are the first defence against infection, followed by the acquired CMI and DTH, which together usually contain further spread of infection within the host.

Factors Which Affect Vulnerability to Tuberculosis Infection 

Tuberculosis

Defects in any portion along this elaborate and still incompletely understood defence pathway could render a host more vulnerable to MTB infection, thereby enhancing transmission. Compared with what is known about the immune defences operative during active TB, relatively little is known about the immune response that contains latent MTB infection. Similarly, the events that trigger reactivation of latent MTB infection are poorly understood. CD4 T cells certainly have an important role in this process, since numerous studies document the higher rates of reactivation in HIV-infected individuals. There is debate, however, about whether HIV infection increases the risk of acquiring TB infection in the first place since this appears to be predominantly determined by macrophage function.

Exposure to both silica dust and silicosis increases the rate of reactivation TB.76–78 Inhaled silica particles damage alveolar macrophage cell membranes, the same cells which MTB typically encounters upon inhalation and deposition in the distal lung. Allison and Hart79 showed that sublethal doses of silica enhanced the growth of MTB in macrophage cultures, and guinea pig exposure studies revealed that inhalation of quartz (a chief component of silica dust) reactivated TB lesions that were healing.80 Still other studies suggest that humoral and cell-mediated immunity may also be altered in silica exposure.81 One would expect silica exposure to enhance MTB transmission as well as disease progression.

It is known from human postmortem studies in which single isolated tubercles are found in the lungs that even a single inhaled droplet nucleus is sufficient in some individuals to initiate MTB infection. Yet as seen by TST or interferon gamma release assay (IGRA) results, not all exposed individuals acquire TB infection, even after comparable types of exposures. Observations like these underscore the variability in human susceptibility to TB, which is generally attributed to differences in immune function, genetics, and concomitant health conditions that predispose to infection and disease.

Epidemiological studies by Stead and colleagues 82,83 specifically suggest an enhanced risk of MTB infection, but not disease reactivation, associated with ethnic or racial background. The authors maintained that these factors were surrogates for the historical selection of populations with innate MTB resistance resulting from the evolutionary pressure of the several hundred-year-old TB epidemic in Europe and North America. Persons in central Africa, Aboriginals, and others isolated from this epidemic pressure remained vulnerable because there was no such selection.82,83 It has long been an accepted tenet of medicine that, once infected with MTB, the latent infection is lifelong, with a small but persistent risk of reactivation to active disease. Occasional observations of skin test reversions in the absence of anergy, with or without treatment, had been dismissed as the exceptions to the rule. 

However, these observations are now supported by reversions in IGRA results. The possibility that transient MTB infection may be part of the pathogenesis of the disease has several implications for transmission. First, skin test surveys may greatly underestimate transmission in populations since infected persons may have already reverted their skin test or IGRA back to negative by the time they were tested. Second, if infection can be transient, progression to disease may depend on reinfection to a degree not previously suspected. Indeed there is evidence that what appears to be high rates of reactivation TB disease among recent arrivals to the United States from high-prevalence areas may in fact represent recent infection or reinfection.84 Finally, if natural MTB infection is often transient, and reinfection is important to pathogenesis, then perhaps vaccines may not be as beneficial as hoped.