Monday, February 12, 2018

Infection without Disease (from Precision Medicine and the Reinvention of Human Disease)

A prior post listed 7 assertions regarding the role of infectious organisms on the human genome. In the next few blogs we'll look at each assertion, in excerpts from Precision Medicine and the Reinvention of Human Disease. Here's the fifth:

Normal defenses can block every infectious disease. Hence, every infectious disease results from a failure of our normal defenses, immunologic and otherwise.

For any given infectious agent, no matter how virulent they may seem, there are always individuals who can resist infection. Moreover, as a generalization, the majority of individuals who are infected with a pathogenic microorganism will never develop any clinically significant disease [42].

As one example, Naegleria fowleri is often found in warm freshwater. Swimmers in contaminated waters may develop an infection that spreads from the nasal sinuses to the central nervous system, to produce an encephalitis that is fatal in 97% of cases [43]. Despite the hazard posed by Naegleria, health authorities do not generally test freshwater sources to determine the presence of the organism. Do not expect to find warning signs posted at swimming holes announcing that the water is contaminated by an organism that produces a disease that has a nearly 100% fatality rate. It is simply assumed that anyone who spends any time around freshwater will eventually be exposed to Naegleria. As it happens, although many thousands of individuals are exposed each year to Naegleria in the United States, only a few cases of Naegleria encephalitis occur in this country. In fact, since Naegleria was recognized as a cause of encephalitis, in 1965, fewer than 150 cases have been reported [44]. Most of the reported cases have occurred in children and adolescents and are associated with recreational water activities [45,46]. The children who develop Naeglerian encephalitis, though exhibiting no signs of immune deficiency, are nonetheless susceptible to Naegleria. What makes these children different from all the other children and adults who were exposed to the same organisms?

Neisseria meningitidis, a cause of bacterial meningitis, can be cultured from nasal swabs sampled from the general population. If N. meningitidis were a primary pathogen, then why doesn’t it cause disease in the vast majority of infected individuals. If N. meningitidis were an opportunistic infection, then why does it typically cause disease in healthy college-age individuals (not immunocompromised individuals)? If this organism is neither a primary pathogen nor an opportunistic pathogen, then what kind of pathogen is it? More importantly, why is N. meningitidis a potentially fatal pathogen in some individuals and a harmless commensal in others [47]?

Organisms that were formerly thought to be purely pathogenic are now known to frequently live quietly within infected humans, without causing symptoms of disease. For example, parasites such as the agents that cause Chagas disease, leishmaniases, and toxoplasmosis are commonly found living in apparently normal individuals. Viruses, including the agents that cause herpes simplex infections and infections by hepatitis viruses B and C, can be found in healthy individuals. Mycobacterium tuberculosis can infect an individual, produce a limited pathologic reaction in the lung, and remain in the body in a quiescent state for the life of the individual. In fact, it has been estimated that about one out of three individuals, worldwide, is infected with Mycobacterium tuberculosis, and will never suffer any consequences. Luckily, asymptomatic carriers of tuberculosis, in whom the there is no active pulmonary disease, are noninfective. Staphylococcus aureus, a bacterial pathogen that is known to produce abscesses, invade through tissues, and release toxins, is also known to circulate in the blood, without causing symptoms, in a sizeable portion of the human population [40].

We now know that potentially virulent organisms are normally tamed within our bodies. Hence, the root cause of every clinical infection results from a deficiency in the defenses of particular subpopulations of individuals.

- Jules Berman

key words: precision medicine, commensals, symbiotes, symbiotic, host organisms, latent infection, jules j berman Ph.D. M.D.

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