[albert (OP)]

Following the question on the program:

We've a dog and a cat - both cared for properly, wormed, innoculated and all that.

My son is still a thumbsucker and despite our badgering demonstrates pretty poor hygiene regarding playing with pets, eating food etc..

Is there a test available to check for the presence of parasitic infections that he (or indeed anyone) might have? I seem to recall hearing that toxoplasmosis can have psychological effects while the individual is unaware that they are infected.

Do I need to worry? How would I know if I was infected?

Albert

[Bored chemist]

I remember that there was a story in new scientist about toxoplasmosis and it definitely said there was some indication of an effect on behaviour even when people were not aware they were infected.
To get that data they must have had a test for infection. My best guess would be to ask your doctor about it.

[chris]

Hello Albert.

There is a test for toxoplasma exposure; usually we look for antibodies. People who have never been infected will not have any antibodies that recognise the parasite, whilst those that have will make antibody, which we can detect.

There are two main "classes" of antibody made during an immune response to infection, IgM and IgG. They can be used to discriminate an acute (i.e. recent) infection from one that occurred historically because IgM is only made at acute timepoints and disappears after a few months, whilst IgG provides longlasting immunity.

So someone with a past history of toxoplasmosis will have IgG in their bloodstream, but no IgM, whilst someone who has recently been infected will make IgM as well.

Toxoplasma is a relative of malaria; it's a so-called coccidian parasite. When an individual first contracts the disease the agent replicates (grows) and seeds itself to every tissue in the body, where it forms dormant tissue cysts. This includes muscle and brain tissues.

When a ***** cat eats a mouse carrying these tissue cysts the parasite comes to life in the gut of the cat and undergoes sexual reproduction, forming new infectious forms that pass out in its faeces to be acquired by other rodents. Humans and other large mammals are incidental "dead end" hosts (because we're not eaten by cats as a rule and hence the parasite cannot complete its lifecycle in us).

Recently scientists have uncovered evidence that the presence of toxo in the brains of infected rodents might alter their behaviour, and this has led to speculation that the same might be true in humans.

In the case of the mouse, toxo-infected animals become less timid. They are more likely to venture out into uncovered ground, and lose their aversion to the smell of cat urine (which usually makes mice scarper faster than a rat down a sewer). This, say researchers, makes the mouse more likely to be caught by a cat, enabling the parasite to complete its lifecycle.

There is some (fairly weak) evidence linking toxo infection with psychological problems in humans. Indeed, the fact that in France 80% of the population test positive for toxo could explain a lot...

[iko]

There is some (fairly weak) evidence linking toxo infection with psychological problems in humans. Indeed, the fact that in France 80% of the population test positive for toxo could explain a lot...

Hi Chris,
welcome Albert!
I was really surprised to find 33 citations
crossing "schizophrenia and toxoplasma" in
PubMed database.
Thank you so much for this information
Here is the most recent:

Toxoplasma gondii in Individuals With Schizophrenia:
Association With Clinical and Demographic Factors and With Mortality.

Dickerson F, Boronow J, Stallings C, Origoni A, Yolken R.
2The Stanley Research Center at the Sheppard Pratt Health System, 6501 North Charles Street, Baltimore, MD 21204.

Background: Increased rates of exposure to Toxoplasma gondii have been found in individuals with schizophrenia as compared with control groups, but the correlates of Toxoplasma exposure in schizophrenia have not been defined.
Methods: We measured IgG class antibodies to Toxoplasma gondii in 358 individuals with schizophrenia. We correlated Toxoplasma antibody status with clinical and demographic variables and examined the effect of Toxoplasma seropositivity on mortality in a follow-up period of up to 5 years. Results: Individuals with schizophrenia who had serological evidence of Toxoplasma infection were more likely to be female but did not differ in age, race, total symptom score, or other demographic or clinical characteristics. However, we found that serological evidence of Toxoplasma was associated with a significantly increased risk of dying of natural causes during the follow-up period (Cox proportional hazard ratio of 4.70; 95% confidence interval, 1.27-17.31, P = .020) adjusted for age, gender, and other clinical and demographic variables.

Conclusions: Toxoplasma infection may confer an increased risk for mortality from natural causes in schizophrenia. An understanding of the pathogenesis of Toxoplasma infections in individuals with schizophrenia might lead to new approaches to the management of this disorder.

Schizophr Bull. 2007 Feb 20; [Epub ahead of print]


...and this is the first catch:

Toxoplasmosis masquerading as a psychotropic side effect.

Pariser SF, Zunich J, Pinta ER.
When treating a patient with neuroleptics or tricyclic antidepressants, it is usually assumed that complaints of blurred vision can be ascribed to the anticholinergic side effects of these drugs. The authors present a patient treated with imipramine and trifluoperazine whose complaints of blurred vision led to the diagnosis of toxoplasma chorioretinitis.

J Clin Psychiatry. 1978 Jul;39(7):631-2.

[iko]

And what about this?
That's reeeally neat!
Me like this stuff:

Drugs used in the treatment of schizophrenia and bipolar disorder
 inhibit the replication of Toxoplasma gondii.

Jones-Brando L, Torrey EF, Yolken R.
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/Blalock 1149, Baltimore, MD 21287-4933, USA. lbrando@jhmi.edu

The exact mechanisms of action of some antipsychotics and mood stabilizers have not been elucidated. Response to these medications can vary among individuals. Recent studies indicate that infection with the parasite Toxoplasma gondii may contribute to the symptoms of schizophrenia in some individuals.
We investigated commonly used antipsychotic and mood stabilizing medications for their ability to inhibit the replication of this organism.We employed a system for testing compounds for in vitro activity against T. gondii. Human fibroblasts (HFF) were treated with test compounds and then exposed to Toxoplasma that has been genetically modified to express cytoplasmic beta-galactosidase. Inhibition by the drugs was determined by spectrophotometric analysis of colorimetric reactions.We tested 12 neuroleptic compounds and found that of these, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro. Valproic acid inhibited the parasite at a concentration below that found in the cerebrospinal fluid and blood of individuals being treated with this medication and displayed synergistic activity with haloperidol and with trimethoprim, an antibiotic commonly used to treat Toxoplasma infections.Several medications used to treat schizophrenia and bipolar disorder have the ability to inhibit the in vitro replication of T. gondii.

Schizophr Res. 2003 Aug 1;62(3):237-44.


Now, just for fun, could vitamin D3
from cod liver oil help alleviating
a chronic Toxoplasma infection?
As usual, the 'evidence' is weak...
but towards a positive effect.
wow

1,25(OH)2D3 inhibits in vitro and in vivo intracellular growth of apicomplexan parasite Toxoplasma gondii.

Rajapakse R, Uring-Lambert B, Andarawewa KL, Rajapakse RP, Abou-Bacar A, Marcellin L, Candolfi E.
Institut de Parasitologie et de Pathologie et Tropicale, de la Faculte de Medecine, EA 3950 Interactions Cellulaires et Moleculaires Hote-Parasite, 3 rue Koeberle, 67000 Strasbourg, France.

The hormonal form of vitamin D, 1,25-dyhydroxyvitamin D3 (1,25(OH)2D3), is implicated in a wide range of functions other than its classical role in calcium and phosphorous homeostasis.
When Toxoplasma gondii-infected BALB/c mice were treated with 1,25(OH)2D3, they succumb to death sooner than their counterparts. But they showed less parasite burden in tissues which was further supported by mild pathological lesions. As an effort to understand the physiological mechanism for the above observation an in vitro study was performed. Fewer parasites were observed when 1,25(OH)2D3 pre-treated murine intestinal epithelial cells were challenged with parasites. Moreover, the observed inhibition was dose-dependent and had a maximum effect with 10(-7)M of 1,25(OH)2D3. However, no observable difference was observed, when pre-incubated parasites were added to cells suggesting that the observed inhibition was a result of an effect from 1,25(OH)2D3 on Toxoplasma intracellular growth.
Our data support the notion that 1,25(OH)2D3 may inhibit intra cellular T. gondii parasite proliferation in vivo and in vitro.

J Steroid Biochem Mol Biol. 2007 Jan 30; [Epub ahead of print]

I begin to think that, perhaps only in a certain percentage
of psychiatric patients, hidden Toxoplasma infection
could contribute to neurologic symptoms and some people
might benefit from long-term anti-Toxoplasma treatment.

Hidden, chronic, paucisymptomatic* and persistent
infections by common pathogens had been quite
underestimated so far.
(see the Helicobacter story in "New cancer theory")
But this is a new century...

* Che?...sorry, I learned
English from a book!
from: Manuel  BBC - Fawlty Towers

http://www.iptv.org/friends/britcom/images/FawltyGasp.jpg

[iko]

Even bipolar disorder (see the 'omega-3 connection'!) and Toxoplasma
has been investigated quite recently:

Infection, treatment and immune response in patients with bipolar disorder
versus patients with major depression, schizophrenia or healthy controls.

Hinze-Selch D.
Department of Psychiatry and Psychotherapy, Christian-Albrechts University, Keil, Germany.

Bipolar disorder is the least studied among the three major psychiatric disorders of schizophrenia, major depression and bipolar disorder. Furthermore, investigations on infection and immunity in bipolar disorder make up only a small portion of the sparse research done on this disorder. However, there are reports that modulation of the immune system and certain infections might be associated with bipolar disorder and that there might be differences between bipolar and the other disorders. The purpose of this paper is to briefly review published data on these issues in bipolar versus the other disorders, and to present an ongoing clinical study on the putative involvement of infection with the parasite Toxoplasma gondii in these three major psychiatric disorders.

Bipolar Disord. 2002;4 Suppl 1:81-3.

[Zoey]

That is some powerful information on psychological symptoms and toxoplasmosis! I'm copying it and sending it to some friends. I will also check on a connection to seizures for 3 reasons. 1. many folks labeled 'schizophrenic' turn out to be having partial complex seizures, which antipsychotic drugs may exacerbate, 2. This might offer another option to explore in looking for the cause of seizures with an unknown origin, and 3. The information may be of value to anyone contending with seizures or psychiatric symptoms.
   Wonder if there are any studies to test people suspected of having "psychiatric disorders" for this parasite prior to confirming a diagnosis.
   Now you will send me to the library looking for links on toxoplasmosis and seizures.   The COL "connection" warrants more exploration.
   In Tucson, AZ I joined a support group for folks with seizure disorders many years ago. One of our members was diagnosed with schizophrenia, not epilepsy. However, when he explained his symptoms they were identical to what those of us with partial seizures experienced, so he fit right in with the group.
Thanks for all this information!

Zoey

[Zoey]

p.s. Maybe this explains the political and social chaos in the U.S.too!
American Journal of Obstetrics & Gynecology - Fulltext: Volume 189 ...Overall, toxoplasmosis seropositivity in the United States. is about 15%, but in other populations the prevalence may be considerably higher. ...
http://www.pt.wkhealth.com/pt/re/ajog/fulltext.00000447-200309000-00056.htm

[iko]

Toxoplasma research in patients affected by psychiatric disorders is going further and certainly we deserve an update around here.  For the discussion, to keep this topic alive. 
A new detailed study from Germany:

A Controlled Prospective Study of Toxoplasma gondii Infection
in Individuals With Schizophrenia: Beyond Seroprevalence.

Hinze-Selch D, Daubener W, Eggert L, Erdag S, Stoltenberg R, Wilms S.
2The Center for Integrative Psychiatry, Department of Psychiatry and Psychotherapy, Christian-Albrechts-University, Niemannsweg 147, D-24105 Kiel, Germany.

Toxoplasma gondii (TG) infection has been reported to be more frequent in schizophrenia. The interaction of the lifelong persisting parasite with the host's immune system involves T-cell/interferon-gamma-induced degradation of tryptophan and provides a challenge to the host well beyond a possible role in the etiology of schizophrenia. The hypothesis we tested in this study was that TG infection may be more frequent (serofrequency) and/or more intense (serointensity) in patients with schizophrenia or major depression compared with psychiatrically healthy controls. In addition, these measures are associated with the clinical course. We did a cross-sectional, prospective investigation of individuals with schizophrenia (n = 277) and major depression (n = 465) admitted to our department (2002-2005) and of healthy controls (n = 214), with all groups adjusted for age and geographic home region. Serofrequency was comparable between the groups, but serointensity was significantly higher in the patients. In individuals with schizophrenia, serointensity was significantly positively associated with C-reactive protein levels and leukocyte counts, and first-episode patients yielded significantly higher serotiters. Immunomodulatory medication was associated with decreased serotiters. In addition, the route of infection appears to differ between patients and controls. Thus, our results support increased host responses to TG infection in the patients, as well as increased titers in first-episode patients with schizophrenia; this may relate to the shifted T-helper 1/2 status described in these patients.
Therefore, we suggest that TG infection, particularly in individuals with schizophrenia, is an important environmental factor in the interaction between psychiatric vulnerability, genetic background, immunomodulation, and the neurotransmitter systems.

Schizophr Bull. 2007 Mar 26;

[iko]

http://pathmicro.med.sc.edu/parasitology/Toxoplasma-lc.gif

Gallery of Histological Sections

Section of brain stained with Giemsa to demonstrate
Toxoplasma gondii cysts and frr trophozoites.

http://home.primus.com.au/royellis/toxgon.jpg

http://www.portable-essentials.com/uploaded_images/beerboxkittens-728202.jpg

[albert (OP)]

Toxoplasma research in patients affected by psychiatric disorders is going further and certainly we deserve an update around here.  For the discussion, to keep this topic alive. 

Jeepers! How expensive is the diagnosis? What's the treatment? Aaaaghhh!

[iko]

Calm down Albert,

We are dealing with so called 'unconfirmed evidence',
still matter of investigation and scientific debate.
It will take just a few decades.
Toxoplasma eradication is cheap: two antibiotics
for some weeks or months (they are intracellular).
Take care

ikod   [^]

[chris]

Hi Iko

the drugs work against replicating toxoplasma infection, but I don't think they are active against the latent tissue cysts - these are metabolically inert most of the time and therefore insensitive to drug action.

A similar situation exists for the bacterium M. tuberculosis, although this can (thankfully) be eliminated. These cells enter a quiescent state during which they are invunerable to anti-tuberculous therapy. That's why a course of treatment needs to last 6 months in order for the majority of the bacteria to have re-awakened for long enough to respond to the drugs. This is part of the reason that this infection is so difficult to treat, that resistant forms (MDRTB) are becoming more common and that the global TB death toll is now 5000 people per day. A sobering thought.

Chris

[iko]

Hi Iko

the drugs work against replicating toxoplasma infection, but I don't think they are active against the latent tissue cysts - these are metabolically inert most of the time and therefore insensitive to drug action.

A similar situation exists for the bacterium M. tuberculosis, although this can (thankfully) be eliminated. These cells enter a quiescent state during which they are invunerable to anti-tuberculous therapy. That's why a course of treatment needs to last 6 months in order for the majority of the bacteria to have re-awakened for long enough to respond to the drugs. This is part of the reason that this infection is so difficult to treat, that resistant forms (MDRTB) are becoming more common and that the global TB death toll is now 5000 people per day. A sobering thought.

Chris

Thank you Chris,

I should have specified better that anti-Toxoplasma therapy could be at least as long as in TB, to allow eradication of intracellular protozoa difficult to reach, metabolically almost inert and consequently less exposed to pharmacological treatment.
Another similar condition is Whipple disease, where the germs have a duplication time over two weeks and daily antibiotic treatment should be continuous  for one or two years.  Even in this case relapses are not infrequent after stopping daily bactrim.  When bacteria or protozoa have been able to reach hyperprotected areas like the central nervous system, any kind of treatment is more difficult and results are not guaranteed.
I read that for particular cases or Q-fever antibiotic treatment for life should be recommended.
Talking about occult persisting infections!
They should be investigated more extensively these days, don't you think?
Now that we have achieved such wonderful diagnostic tools like PCRtests, that allow direct detection of pathogens...not INDIRECT search for specific antibodies, we seem to have lost interest in underdiagnosed occult infections and their hypothetical consequences (autoimmunity, some lymphomas, etc).
Is this happening for a mere lack of funds and investment money or what?

iko

[iko]

I read that for particular cases or Q-fever antibiotic treatment for life should be recommended.
Talking about occult persisting infections!
They should be investigated more extensively these days, don't you think?
Now that we achieved wonderful diagnostic tools like PCR, we seem to have lost interest in underdiagnosed occult infections and their hypothetical consequences (autoimmunity, some lymphomas, etc).
Is this happening for a mere lack of funds and investment money or what?

iko

This is a 'rare' example of overlapping between a typical autoimmune disease (dermatomyositis) and an acute Toxoplasma infection:

[A case of toxoplasmosis with dermatomyositis] [Article in Japanese]

Kawakami Y, Hayashi J, Fujisaki T, Tani Y, Kashiwagi S, Yamaga S. Department of General Medicine, Kyushu University.

We report a case of dermatomyositis (DM) in a 15-year-old female with toxoplasmosis after ingestion of raw bovine liver. Facial erythema and cervical lymphadenopathy preceded myalgia and muscle weakness of the extremities. The diagnostic criteria of DM was fulfilled because of symmetrical and proximal dominant muscle weakness, elevation of myogenic enzyme (CPK, GOT, LDH, myoglobin, aldorase), myogenic pattern of electromyogram, skeletal muscle biopsy showing interstitial myositis with mild destruction of muscle fiber, and facial erythema. Immunological findings showed IgG anti-toxoplasma antibody to be 1340 IU/ml and IgM to be 7.0 (Cut off index 0.7), suggesting acute toxoplasmosis. Treatment with prednisolone for DM and acetylspiramycin for toxoplasmosis was successful. Toxoplasmosis should be considered as a possibility in patients with myositis.

Kansenshogaku Zasshi. 1995 Nov;69(11):1312-5.




Dermatomyositis responding to treatment of associated toxoplasmosis.
Harland CC, Marsden JR, Vernon SA, Allen BR.
Department of Dermatology, University Hospital, Queen's Medical Centre, Nottingham, U.K.

We report a 59-year-old woman with severe dermatomyositis in association with high serum toxoplasma antibody titres who was successfully treated with pyrimethamine and sulphadiazine. This case supports an aetiological role for toxoplasmosis in the pathogenesis of some cases of dermatomyositis.

Br J Dermatol. 1991 Jul;125(1):76-8.

Causes of Dermatomyositis

The cause of dermatomyositis is unknown; however, the following factors have been implicated:

A genetic predisposition may exist. Dermatomyositis rarely occurs in multiple family members, but it may be linked to certain human leukocyte antigen (HLA) types (eg, DR3, DR5, DR7). In addition, polymorphisms of TNF-alpha have been linked to photosensitivity in patients with dermatomyositis.

Immunological abnormalities are common in patients with dermatomyositis. Patients frequently have circulating autoantibodies. Abnormal T-cell activity may be involved in the pathogenesis of both the skin and the muscle disease. In addition, family members may have other diseases associated with autoimmunity.

Autoantibodies to nuclear antigens (ANA) and cytoplasmic (ie, antitransfer RNA synthetases) antigens may be present. Although their presence may help to define subtypes of dermatomyositis and polymyositis, their role in pathogenesis is uncertain. Infectious agents, including viruses (eg, coxsackievirus, parvovirus, echovirus, human T-cell lymphotrophic virus type 1 [HTLV-1], HIV) and Toxoplasma and Borrelia species, have been suggested as possible triggers of the disease.


Several cases of drug-induced disease have been reported. Dermatomyositislike skin changes have been reported with hydroxyurea in patients with chronic myelogenous leukemia or essential thrombocytosis. Other agents that may trigger the disease include penicillamine, statin drugs, quinidine, and phenylbutazone.

Dermatomyositis may be initiated or exacerbated by silicon breast implants or collagen injections, but the evidence for this is anecdotal and has not been verified in case-control studies. A recent report detailed HLA differences among women in whom inflammatory myopathy develops after they received silicone implants.

more reading from:  http://www.emedicine.com/MED/topic2608.htm

[iko]

Toxoplasmosis and Chronic Myeloid Leukemia

Several cases of drug-induced disease have been reported. Dermatomyositislike skin changes have been reported with hydroxyurea in patients with chronic myelogenous leukemia or essential thrombocytosis. Other agents that may trigger the disease include penicillamine, statin drugs, quinidine, and phenylbutazone.

more reading from:  http://www.emedicine.com/MED/topic2608.htm

Toxoplasma may cause dermatomyositis.
Dermatomyositis rarely goes together with CML:
Could Toxoplasma cause some case of CML?

I don't know if we can play this game.
It is late in the evening, professors and
real scientists are probably all busy
writing their papers and don't have time
for silly forums...

There are no known causes for CML.
The discussion is open: it's an experiment!
Allowed search engines:  Google - PubMed.
Enjoy

iko

I remember one case only of acute toxoplasmosis in a patient with newly diagnosed CML.
Surely that's a coincidence, nevertheless you may start searching for other hints:

Cutaneous toxoplasmosis.

Leyva WH, Santa Cruz DJ.
A case of epidermotropic cutaneous toxoplasmosis is reported. The patient, a 53-year-old man with chronic myelogenous leukemia in blast crisis, received a bone marrow allograft but continued to have severe pancytopenia. Numerous diffuse, palpable, purpuric nodules appeared 21 days after the transplant. Organisms were found within the epidermal keratinocytes--both singularly and in cysts. Dermal and neural infiltration was also present. Toxoplasma gondii was identified on the basis of the ultrastructural features of the parasite. Possible sources of infection include reactivation of a previous latent infection, transmission through a bone marrow allograft, or nosocomial acquisition.

J Am Acad Dermatol. 1986 Apr;14(4):600-5.




Here you have different hypotheses:
- Reactivation of a latent infection helped by immune depression from leukemia and treatment.
- Infection transmitted through the bone marrow graft (but 21 days is a bit too fast!).
  These two suggestions support the 'opportunistic theory': germs prevail BECAUSE of the leukemic process, are very dangerous, but totally unrelated to the real cause of that particular type of leukemia (Lymphoid or myeloid).
In this context, infectious agents are frequently defined 'innocent by-standers' instead of 'implicit bastards' (more appropriate, in my personal opinion).

- Occult persistent infection (infestation: they are protozoa) unmasked in terminal phase. Toxoplasma and consequent abnormal overridden immune reaction might have stimulated a previously inactive clone of CML precursors and started the leukemic process itself over weeks and months, replacing normal hemopoietic cells and invading liver, spleen and marrow.
Little CML clones may harbour in normal people and represent the result of a somatic mutation.
Percentage of 'positive' healthy carriers of tiny CML clones would obviously increase with age.
So another factor is needed to justify the expansion of the mutated clone.
Toxoplasma could be one of a restricted group of germs capable of jamming some crucial point of the complex immune reaction (involving T-cells, macrophages, complex cytokine interactions) evoked by protozoa and other 'fastidious' germs.
Helicobacter pylori and mycoplasmas might be in the number.

 

[iko]

More than thirty years ago a French group reported that:
 "The frequence of high serological titres (i.e.: lots of anti-Toxoplasma antibodies) seems to be greater among patients suffering from chronic myeloid leukemia than among another people"...but in the following decades these observations were not either confirmed or implemented by the new diagnostic tools available.

[Toxoplasmosis and chronic myeloid leukemia][Article in French]

Beauvais B, Garin JF, Lariviere M, Languillat G.
A patient suffering from chronic myeloid leukemia and used as a donor of leucocytes was found to have toxoplasmosis associated with a high level of IgG without an elevation of IgM which was maintained for several months. This case raises several points for discussion. Toxoplasmosis is a frequent complication of malignant hematological disease, it is often severe with neurological complications in more than half the patients affected. It is often difficult to diagnose. The parasite is arduous to isolate and serology is problematic to interpretate without reference to previous samples. This suggests it would be wise to measure the titre of anti-toxoplasma antibodies as part of the initial investigations of every malignant hemopathy and to repeat the measurements during the evolution of the disease. Any patient showing a high serological titre, even though it is stable and without IgM should be given systematically a specific treatment for toxoplasmosis, for as in the patient presented in this paper, such a serological picture is compatible with an increasing infection. The frequence of high serological titres seems to be greater among patients suffering from chronic myeloid leukemia than among another people. Then, transfusion of leucocytes of such patients may be the source of parasite transmission; this paper relates one case of post-transfusional toxoplasmosis.
Nouv Rev Fr Hematol Blood Cells. 1976;16(2):169-84.

In this case of CML, parasites were so many in peripheral white cells to be trasferred into the recipient of a granulocyte transfusion and start acute toxoplasmosis.  CML patients have plenty of mature granulocyte in their blood: these ready-to-combat-germs cells were harvested and transfused to acute leukemia patients after chemotherapy, who had no white cells and overwhelming infections.
Today this practice has been abandoned.

[iko]

Bits and pieces from the past, difficult to track: neither the abstracts are available!

An autopsy case of toxoplasmosis associated with myelocytic leukemia.

Kishida S, Yoshie Y, Hamamoto Y.
Acta Pathol Jpn. 1974 Jul;24(4):541-50. 

[Toxoplasmosis and generalized mycosis after treatment of chronic myelosis (author's transl)] [Article in German]

Musil A, Friedrich E.
Zentralbl Allg Pathol. 1973;117(2):110-7.

Facts do not cease to exist because they are ignored

Aldous Huxley 

from:  New Cancer Theory

[iko]

Good news about Toxo tricky hide-and-seek techniques!
from:    Science Daily May 12, 2007
Source:  Imperial College London
http://www.sciencedaily.com/releases/2007/05/070510110538.htm

Toxoplasmosis Infection Trick Revealed By Scientists

Scientists have provided new insight into how the parasite which causes toxoplasmosis invades human cells. Toxoplasmosis is a parasitic disease, primarily carried by cats. It is transmitted to humans by eating undercooked meat or through contact with cat faeces.
...
It is particularly dangerous for pregnant women, whose foetuses can be infected via the placenta, and those with a weakened immune system, such as people infected with HIV. In severe cases, toxoplasmosis can cause damage to the brain and eyes, and even death.
...
Now researchers from London and Geneva have determined, for the first time, the atomic structure of a key protein which is released onto the surface of the parasite just before it invades host cells in the human body. They found that the protein known as TgMIC1 binds to certain sugars on the surface of the host cell, assisting the parasite to stick to, and then enter the human cell.
...
Using a novel carbohydrate microarray the team were able to identify the precise sugars to which the parasite protein binds. Following this the team used a combination of NMR spectroscopy and cellular studies to characterise the behaviour and interactions of the parasite protein and host cell sugars. This means that the team have a more detailed picture than ever before of exactly how the parasite recognises and attacks host cells in the body.

Professor Steve Matthews from Imperial College London’s Division of Molecular Biosciences, one of the paper’s authors, explains the significance of the research, saying: “Understanding the fundamental, atomic-level detail of how diseases like toxoplasmosis pick out and invade host cells in the human body is vital if we want to fight these diseases effectively.

“Now that we understand that it’s a key interaction between a protein on the parasite’s surface and sugars on the human cell which lead to the cell’s invasion, there is potential to develop therapeutics that are targeted at disrupting this mechanism, therefore thwarting infection.”

Toxoplasma gondii, the parasite that causes toxoplasmosis, is one of the world’s most common parasites. Around a quarter to half of the world’s population is thought to be infected, and around 1% of people in the UK catch toxoplasmosis each year. In the majority of cases, those affected don’t have any symptoms. But for those with weakened immune systems, and unborn babies, toxoplasmosis can cause very serious health problems.

Reference:
 ‘Atomic resolution insight into host cell recognition by Toxoplasma gondii’,
 The EMBO Journal, 10 May 2007.

Note: This story has been adapted from a news release issued by Imperial College London.

http://www.sciencedaily.com/images/2006/08/060816020833.jpg
Toxoplasma gondii cyst in brain tissue. (Image courtesy of U.S. Centers for Disease Control and Prevention)

[iko]

So another factor is needed to justify the expansion of the mutated clone.
Toxoplasma could be one of a restricted group of germs capable of jamming some crucial point of the complex immune reaction (involving T-cells, macrophages, complex cytokine interactions) evoked by protozoa and other 'fastidious' germs.
Helicobacter pylori and mycoplasmas might be in the number.

Another 'coincidence' buried in a prestigious
journal like the New England J. of Medicine
ten years ago.  Everybody laughs when I say
that the real title should actually be:
   "A Mother Nature's Lecture on CML"

Spontaneous remission in a patient with chronic myelogenous leukemia.

Musashi M, Abe S, Yamada T, Tanaka J, Gotohda Y, Maeda S, Sato Y, Morioka M, Sakurada K, Minagawa T, Asaka M, Miyazaki T.
Third Department of Internal Medicine, Sapporo, Japan.

N Engl J Med. 1997 Jan 30;336(5):337-9.

Unfortunately there is no abstract and full-text is not free, but as a
NEJMed subscriber I think I am allowed to write a short summary for you:

Case Report
A 45-year-old man was referred to our hospital for evaluation of leukocytosis in January 1985. Three months previously, he had reported tarry stools.
A peptic ulcer was diagnosed and treated with intravenous cimetidine. At that time, leukocytosis, thrombocytosis, and anemia were detected. A bone marrow aspirate showed marked myeloid hyperplasia. Cytogenetic analysis revealed Ph-positive cells in the bone marrow, and a diagnosis of CML was made. During the next month the leukocyte count decreased to 14,400 per cubic millimeter, but it subsequently gradually increased to 31,800 per cubic millimeter before admission to our hospital.
Physical examination on admission revealed anemia and mild hepatosplenomegaly. A complete blood count again showed leukocytosis and thrombocytosis. The neutrophil alkaline phosphatase score was 94 (normal range, 170 to 335). Plasma histamine and prostaglandin E concentrations were within the normal range.
An endoscopic examination revealed an ulcer scar in the duodenal bulb.

Regular follow-up, without chemotherapy, was planned for the patient. In February 1985, the hepatosplenomegaly disappeared. The leukocyte count and platelet count returned to normal in April 1985. As of January 30, 1996, the patient had been well, without any signs of recurrence, for 11 years. Blood counts since June 30, 1994, have been normal.
...

In 1984 the 'infectious theory' of peptic ulcer was still a matter of debate (1).
Consequently the word helicobacter cannot be found through the whole text (but it's a 1997 paper!).
Intravenous cimetidine had been available for several years, and found quite useful for healing peptic ulcers, and probably making life difficult to H. pylori as well.
In the past, cimetidine had been reported to have also an immunomodulating activity.
Something surely happened in that patient during the following weeks and months, and chronic myeloid leukemia (confirmed by more sophisticated tests over the following years) pulled back gently.
Average survival rate for CML was about <5 years then, with 1/3chance to find a donor for BMT.
In 2000 STI571-Gleevec-Imatinib (2pills/day - no BMT) finally came and life became much easier for CML patients.  According to some distiguished scientists, this new drug actually represents, in oncology, the most important achievement in the last two decades.
Thanks to Dr. Brian Druker and his colleagues from Oregon.
In 2000 that japanese man just turned 60, hopefully healthy and CML free.

ikod   [^]




1)  click down here for "Helicobacter connection"

CML Treatment

Treatment options and outcome from treatment have improved significantly over the years.


Year          Treatment          Survival (months)
 
1920-1950     Splenic irradiation         28
 
1950-1960     Busulfan                   35-45
 
1960-1970     Hydroxyurea                48-67
 
1970-1980     1st Allogeneic Stem Cell Transplant for CML
                                    50-60% CURE
 
1980-1990     IFNa (Interferon alpha)    55-89
 
1990-2001     IFNa + Cytosine arabinoside (Ara-C)
                 Recent studies showing significant improvement over IFNa alone
 
1995-2001     STI-571                >90% 5yrs survival (2007)


Table 1. Treatment options and survival. (JAMA, August 22/29 p. 896)

from:  http://intmedweb.wfubmc.edu/grand_rounds/2001/myeloid.html