Devoted to the topic of data specification (including data organization, data description, data retrieval and data sharing) in the life sciences and in medicine.
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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