Two
Detailed Cased Histories Involving Patients with Co-Infections—
Babesiosis, Ehrlichiosis, and Lyme Disease
Virginia
T. Sherr, M.D.
May, 2004
Brief Abstract
Medical and laboratory
data from a patient marital couple illustrate the potential seriousness
and persistence of increasingly common protozoan, rickettsial, and spirochetal
infections. Such case histories demonstrate immediate need for intensive
education of all physicians and the public about the risks posed by tick-borne
infections. Experiences of these 2 patients demonstrate necessity for accurate
epidemiological reporting of all such vector-borne diseases. Of the titled
infections, only Lyme and ehrlichiosis are on the Center of Diseases Control’s
list of Officially Reportable Diseases.
Descriptions of the patients’ symptoms
Mr. W’s infection— unrecognized chronic Lyme
disease initiated a medical controversy
Mr. W, an active 76-year-old
man (1996) upon his first ever visit to a psychiatrist’s office, needed
evaluation due to marked changes in his personality. Careful history-taking
revealed that he had experienced a rectangular dark red rash on 1 ankle
(otherwise asymptomatic) for several weeks circa June 1996. By late that
summer, he had gradually developed uncharacteristic and inappropriate outbursts
of extreme irritability, altered gait, loss of direction sense, evening
chills, episodic daytime sleep urgency, pronounced executive memory loss
and variable loss of recent memory. Neurologic and psychiatric workups ensued.
In September 1996, his neurologist diagnosed Lyme disease (LYD) when an
enzyme-linked immunosorbent assay blood test revealed a positive IgG of
2.63. Doxycycline 100 mg twice daily was begun. Mr. W became less symptomatic,
his rages abated, and his memory improved. Another specialist, however,
questioned accuracy of the diagnosis, terminating the antibiotic after 2
weeks. Axillary lymphadenopathy remained unexplained.
As June 1997 approached,
Mr. W’s sore left knee was visibly swollen. Nine months after original
diagnosis, he also had developed balance problems, strange, shifting, tender,
acutely painful areas on his scalp and feet, and a highly distracting, tingling
sensation on the tip of his nose. His family physician examined him and
confirmed the original diagnosis of persistent, neuro-Lyme disease.
On 6/3/97, prior to
antibiotic treatment, Mr. W suddenly experienced an episode of violent,
seizure-like shaking of his entire body, during which he did not lose consciousness.
(1,2) There were no urinary tract
or other symptoms. His LYD Western Blot (WB) test (7/9/97) revealed 4 highly
significant positive IgG bands plus another: an equivocal band on the same
WB test for immune antibodies relating to the causative spirochete, Borrelia
burgdorferi (Bb).(3)
Gradually improving
but still symptomatic following several months of oral antibiotics, Mr.
W’s WB immune response increased to show 6 positive, significant, IgG
antibody bands against Bb. (4/8/98). Intensive antibiotic treatment consisted
of concomitant oral cefuroxime axetil, cefixime and doxycycline 100 mg three
times per day. His knee swelling totally subsided. Later, receiving azithromycin
alone, the patient’s irritability, disorientation, cognitive problems,
and all but 2 other symptoms resolved. He retained his intense need for
lengthy daytime naps despite sound nighttime sleep and he experienced episodic
afternoon chills despite normal body temperature. He had episodes of dark
urine. Diagnostically, however, physicians did not consider babesiosis early
on.
When waves of daytime
narcoleptic-like sleep attacks and chilliness intensified during evening
hours, despite the use of antibiotics, and Mr. W complained that winter’s
coldness depressed him, he was further evaluated. On 3/26/98, his blood
tested positive with a 1:512 indirect fluorescent antibody (IFA) titer for
Babesia microti at BBI (now “Specialty”) Laboratory. His
B microti polymerase chain reaction (PCR) was also positive (7/7/98)
at Medical Diagnostic Laboratories (MDL). Treatment rounds of anti-protozoan
medications atovaquone (Mepron) and azithromycin (Zithromax) were undertaken
for babesiosis.
Overview of the husband’s follow-up laboratory findings
and treatment of babesiosis
Fifteen months into treatment
by a LYD specialist (4) for chronic babesiosis and LYD,
the patient’s B microti PCR turned negative but his B burgdorferi
DNA (PCR at MDL) was positive. Mepron was stopped and antibiotic treatment
continued. When symptoms resurged in approximately 1 year concomitant with
an increasing Human Monocytic Ehrlichiosis (HME) titer, restarting his doxycycline
(9/27/00) provided general relief and resolution of lymphadenopathy. However,
by April 2001, Mr. W’s disorientation, chilliness and sleep urgency intensified
once more. His PCR for B microti DNA again returned positive, as did
his WB for the same organism (MDL).
Because of the positive
direct blood test for B microti DNA, clinical improvement from LYD
symptoms, and the first time fully negative Lyme IgG WB, new emphasis began
on re-treatment of chronic babesiosis (5/02). Mr. W received the anti-malarial,
Malarone (atovaquone with proquanil), but he also was given a course of
dirithromycin (Dynabac) to maintain suppression of likely persistent subclinical
borrelial infection. Rationale was that presence of co-infections greatly
magnified severity of each. Eventual return of original Lyme disorientation
and knee symptoms, however, unveiled resurgences of Lyme WB IgG antibodies
(now up to 7 significant bands, 1/30/02—IGeneX Lab) and at MDL, an
increase to 3 Babesia antibody bands.(5) At no time
did Mr. W need psychotropic medications, other than the stimulant described
below.
Interpretation of Mr. W’s experience with babesiosis
Mr.W had multiple cycles
of treatment with antimicrobial medications (atovaquone, azithromycin, and
a combination of atovaquone and proquanil) throughout 4 years with much
improvement in memory, affect and general health. Both direct PCR evidence
of Babesia infection and indirect Babesia tests (increasingly positive
antibodies) remained confirmatory of his having active chronic babesiosis.
When anti-babesia medication lapsed, there were returns to lab and clinical
abnormalities.
Persistent daytime
sleep urgency despite lengthy antimicrobial treatment, and 6 PM daily chills,
may have been residual signs of chronic babesiosis. However, the narcolepsy-like
symptom cannot totally be separated from LYD. Direct evidence of both Lyme
and babesiosis was still present by positive DNA testing in April 2001 and
by increasing antibodies to both in January 2002. Recent intensification
of his sleep attacks coincident with current absence of anti-protozoan treatments
suggests babesiosis causation. Modafinil (Provigil) 200 mg twice daily greatly
improved his wakefulness. Recent developments of positive PCRs for mycoplasma,
HHV-6 and a newly developed mild sleep apnea imply possibility of additional
causations of his increasing sleep urgency. Of significance, likewise, there
are now diminished blood levels of androstenedione, ACTH, ADH and MSH and
increased osmolality—a syndrome frequently seen following illness due
to chronic neurotoxic diseases (6) such as Lyme disease
and a methicillin-resistant coagulase-negative naso-pharyngeal infection
that was diagnosed and treated.
Mrs. W’s infections, laboratory findings and treatment
Mrs. W’s initially
unrecognized tick-borne disease manifested neurologically and muscularly.
A 66-year-old gardener, she accompanied her husband for evaluation. She
described a medically-observed, ring-shaped red rash on the skin of one
forearm (1990). At least 3 other similar rashes were observed in the years
surrounding that event—2 had the appearance of a “bull’s
eye.” Seronegative by the ELISA and conventional WB tests, and having
no “flu-like symptoms,” Mrs. W was not considered by specialists
to have a treatable tick-borne disease (TBD) until 1997 when chronic neuroborreliosis
with multi-system Lyme involvement was diagnosed clinically by her family
doctor. Among many symptoms were profound sense of coldness, entire bodily
weakness and generalized, painful, severe muscular spasms, cardiac laboring
and arrhythmias, waves of painful aural, visual, and touch hypersensitivities,
aphonia, a maxillary bone-gum fistula, bradypnea, impatience, multiple sclerosis-like
neurological symptoms, chills, and losses of visual acuity. Ocular examination
showed a punctate retinal hemorrhage. She appeared on the verge of imminent
collapse. Babesiosis originally was not a suspected co-infection.
Mrs. W’s intensive,
8 months’ treatment with intravenous (IV) medications—ceftriaxone
followed by IV cefotaxime for treatment of the persistently severe late-stage
neuro-LYD symptoms, led to a steady improvement. Attempts to truncate treatment
resulted in memory losses and return of muscle pain. She also had received
doxycycline 100 mg three times daily for newly resurgent Human Monocytic
Ehrlichiosis. Her neurological symptoms, restless legs syndrome, cardiac
laboring, unrelenting muscle pains, and generalized weakness slowly lessened
but recurred with each attempt to discontinue antibiotics.
Gradual relief continued
until January 1998 when treatment for LYD suddenly appeared to falter. While
still on IV cefotaxime, symptoms intensified with multiple daily waves of
skin flushing, sweating, cardiac arrhythmias, pricking, burning, or searing
cutaneous pains, weakness, chills, painful muscle spasms, generalized itching,
severe hyperacusis, blurred vision, parched lips, impatience, irritability,
clumsiness, insomnia, and exquisite hypersensitivity to touch. Episodic
scalp and facial sweating occurred in waves with concomitant late afternoon
malaise and episodic chills.
IFA blood tests for
Babesia then revealed a high titer of 1:512 (BBI). However, Mrs.
W was afebrile, with subnormal oral temperatures (7)
usually ranging from 95.7 to 97.0º F Historically, the patient had experienced
unexplained blood losses during 2 otherwise uneventful elective surgeries,
one preceding and one following this crisis time by several years, although
other routine hemograms were consistently normal. Oral iron (300-600 mg/day)
restored her postoperative Hgb from 8% to 14.5% each occasion but did not
stop profound malaise and episodic chilliness.
Overview of the wife’s laboratory findings and treatment
of babesiosis
Mrs. W’s initial
Babesia antibody test, negative (1/05/98), was first done many months
after IV and oral treatments, including azithromycin, were started to treat
her chronic neuroborreliosis (July 1997). She still was being treated for
both LYD and ehrlichiosis and symptoms from these were resolving slowly
when daily waves of malaise dramatically escalated, incapacitating her in
her 8th month of IV antibiotic treatment. Babesiosis was reconsidered diagnostically.
On 3/26/98, IFA tests
for B microti done at BBI Laboratory revealed the above-mentioned
strongly positive babesiosis titer. Babesia PCR blood DNA testing
also was positive a year later (March 1999, IGeneX Laboratory), following
partial treatment with atovaquone and azithromycin for her newly recognized
chronic babesiosis.(8,9) Thus, three
independent laboratories confirmed positive testing for B microti.
In addition, a Fluorescent in situ Hybridization (FISH) test (IGeneX) was
positive for fluorescing merozoite ring forms of Babesia piroplasms.
MDL Lab also found Mrs. W’s PCR test for Lyme DNA positive (11/8/99).
Of additional interest, when the 2 other known diseases were diminished
by treatment, there was a return of a variety of symptoms. Ehrlichiosis
antibody (HME IgM) titers were then found to have risen to 1:160 (November
1999, IGeneX Lab). Symptomatic relief followed re-treatment with doxycycline.
In April 2001, Mrs. W again had evidence of babesiosis via a positive B
microti WB (MDL). Her Lyme tests now showed 3 significant positive bands
on the IgM WB—a known marker for chronic as well as acute LYD.
(10)
Interpretation of Mrs. W’s Experience
Intensive treatment
for babesiosis and Lyme disease over the span of 4 years returned a handicapped
Mrs. W to much improved capacity. However, her life still has to be managed
around 2–9 milder daily waves of likely Babesia-provoked symptoms.
Chills subsided temporarily when atavoquone and zithromycin were
prescribed. Later, as with her husband, a nasopharyngeal culture was positive
for the newly discovered neurotoxin-former, methicillin-resistant, coagulase
negative Staphylococcus epidermidis that had contributed to her discomfort
prior to its specific antibiotic treatment.(6)
Summary of Both Cases
Mr. and Mrs. W, both
of whom have documented cases of chronic tick-borne illnesses, including
babesiosis, have lived in Pennsylvania most of their lives. Lesions appeared
after gardening in their wooded, deer-populated, backyard north of Philadelphia.
Neither spouse has been re-exposed to ticks.
Both partners have
had normal MRIs. However, single-photon emission computed tomography (SPECT)
scans of their brains revealed “global heterogeneous hypoperfusion”
compatible with impact of noxious influences upon cerebral circulation,
cited by the radiologist as likely related to the LYD of each.(11)
For one partner microscopically fluorescing intra-erythrocytic parasites
were found in 3 widely spaced evaluations. Neither mate had the acute babesia
signs of splenic enlargement or severe hypotension.(12)
They were not tested for urinary hemolysis until after atavoquone treatment
(13) when these tests were negative. Diagnoses of babesiosis
eventually helped to partially explain the inability of both patients to
recover fully despite intensive treatment for LYD. Treatment then, for B
microti infection, sufficiently restored both partners so that they
can pursue physical and cognitive activities, although neither is asymptomatic
or fully recovered.
Conclusions
Lack of general medical
awareness of the presence, persistence, and severity of these widely epidemic
and backyard-located, spirochetal, rickettsial and protozoan infections
caused significant delay in the treatment of this couple. The delay prolonged
their illnesses resulting in severe discomfort and long-term disabilities.
Early recognition and medical intervention could have prevented much of
the ultimate persistence of their infections.(14)
Official recording
of all vector-borne illnesses in humans needs to be instituted, in
order to bring to universal awareness the true scope of the epidemic and
the necessity of proper differentiation and treatment of such infections
as Lyme disease, ehrlichiosis, and babesiosis.
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