June 25, 1999 

Initial analytic steps

Michael's medical history and laboratory data have led me in a new direction.
Among the autism-spectrum children whose similar data I've perused, most kids
have data and history pointing towards or implicating one or several of the
herpes viruses, occasionally with missing antibody titres for vaccinal antigens
and/or other immune irregularities. 

In many cases (n<15), less specific lab tests (eg, WBC, RBC, NK count and
function) have been consistent (i) with the child's titres for CMV, EBV, and/or
HHV6, and (ii) with hematopoietic and peripheral effects associated with those
viruses. Although often reinforced by a child's medical history, that these
consistencies arise amidst complex lab data adds value to a biological model
specific for that child.

Whereas Michael's medical history contains elements similar to what occurs for
many autism-spectrum children (eg, loss of language, chronic gastrointestinal
problems), his lab data thus far do not implicate herpes viruses and and their
effects upon bone marrow function. 

Nonetheless, while looking for signs of cytopenia and skewed immune-cell
subsets, that his monocyte count has increased in recent months caught my eye,
as did his variance from reference ranges in regard to several iron-related
measures. Nonetheless, at this time these divergences do not appear so severe
as to suggest monocytosis with cytopenia and anemia (1), though the various iron
measures may be providing significant clues for Michael.

Instead, many aspects of his medical history and laboratory data are consistent
with persistent intestinal colonization and translocation by Klebsiella
pneumonia and hemolytic Escherichia coli (Kp, hEc). For instance, Michael has
mild elevations of several vaccinal antigens, and Kp is known as a polyclonal
activator of immunoglobulin production; ivIg generally is ineffective against
Kp, although anti-Kp hyperimmunoglobulin preparations can be effective; and
dietary fatty acid modulations may have altered and improved macrophage function
against Klebsiella pneumonia.

In contemplating the possible effects of Kp and hEc in Michael, the following
rationale was researched. Are these bacteria likely to translocate? Can they
induce immune impairments, abdominal problems and neurologic deficits? To each
question, the answer is yes. 

When combined with evidence of Michael's severe dysbiosis and Kp/hEc
colonization, and in the absence of lab data implicating alternative
possibilities, the range of symptoms associated with Kp and hEc in medical
literature suggest the likelihood that Klebsiella pneumonia and hemolytic
Escherichia coli are etiologically significant factors in Michael's
gastrointestinal and abdominal problems, and neurologic deficits. 

We might wonder whether the common mucosal immune system and the bidirectional
communication between nerve endings and macrophages suggest that intestinal Kp
and hEc may also be contributing to Michael's increaseing oral-hypersensitivity.

Whereas Kp and hEc appear to be extremely important to Michael's past and
current medical history, participation by other pathogens cannot be ruled out
at this time. Loss of language can be induced by Herpes simplex and varicella,
and these viruses can induce oral-motor problems and can be present within the
CNS of individuals having no peripheral signs or symptoms (2). Similarly,
cytomegalovirus can be acquired in utero or neonatally, can be seemingly
asymptomatic, is associated with increased intestinal permeability, and has been
documented within persons having no peripheral anti-CMV antibodies. 

Other pathogens that came to mind in accord with Michael's medical history
include (i) CMV, EBV, and HHV6 because of their associations with chronic
fatigue syndrome; (ii) mumps because of its association with oligospermia; and
(iii) enteroviruses such as Coxsackie because anti-enteroviruses were not
assayed. 

Among these possibilities, significant participations of EBV and HHV6 seem less
likely because their antibodies titres are within range and because myeloid-cell
subsets are not profoundly shifted. 

For reasons such as these, the more I looked at Michael's history and lab data,
the more I came to sense that Kp and hEc are etiologically significant to his
mesenteric and neurologic challenges, even as other pathogens (eg, CMV,
Coxsackie) may also be present and significant.

The most striking feature of Michael's lab data is the sustained presence of two
bacteria having a range of potential sequelae; and these pathogens, possibly
augmented by another such as CMV or Coxsackie, may have contributed to his
decline pursuant to his MMR and HepB vaccination shortly after his first
birthday.

That he is called bright, despite language problems, is important because these
observations probably reflect a goodly amount of retained cognitive function.

I believe that Michael would be well served if his parents and physicians were
to consider (a) certain additional tests to rule out or determine the extent of
possible bacterial translocation, and (b) to explore aggressive pharmaceutical
interventions to minimize his Kp and hEc colonizations. 

These infections are important; reducing their presence would be beneficial.


Teresa Binstock
Researcher in Developmental and Behavioral Neuroanatomy
June 25, 1999

1. Evaluation of a child with monocytosis and cytopenia and anemia

 
2. A citation-full but rambling exploration of HSV's neurologic effects

 
3. To rule out Coxsackie and occult CMV and to identify the strain or strains
of Klebsiella pneumoniae, and to ascertain their spread, if any, into mesenteric
and other tissues; also, several additional immune function tests would be
instructive. These various tests are more fully delineated on the "Additional
tests" page linked hereinabove.

 Summary Why Klebsiella pneumonia and hemolytic E. coli have come to demand much attention in this report. (Kp, hEc)

 Translocation of Kp and hEc

 Peritoneal and abdominal Kp and hEc

 Neurologic aspects of Kp and hEc

 Miscellany regarding Kp and hEc

 Additional tests

 Michael's index page

     A series of autism-spectrum research monographs is available by
     links on a web page: http://www.jorsm.com/~binstock/index.htm