Chronic Fatigue Syndrome

A Roadmap for Testing and Treatment





Introduction
Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME) and usually abbreviated to ME/CFS, is an immunological and neurological disease characterized by fatigue, post-exertional malaise, cognitive dysfunction, mood disorders, and an array of other symptoms.

The following guidelines will help you determine: (1) whether you have chronic fatigue syndrome (ME/CFS), and if so: (2) which laboratory tests can be performed to identify the infections and other factors that may underpin your ME/CFS, and: (3) what therapies you can follow to address these infections and factors, and treat the symptoms that arise from your ME/CFS.

This roadmap is quite a lengthy document. If you would prefer to begin with a much briefer and simpler overview of the range of tests and treatments provided in this roadmap document, please see the mini roadmap.



Chronic Fatigue Syndrome Diagnosis
There are currently no laboratory tests or biomarkers that can be singularly used to diagnose chronic fatigue syndrome, so diagnosis is performed on symptoms alone. ME/CFS manifests a whole array of clinical symptoms, both physical and mental/cognitive, which typically include the following (patients may not have every symptom):

SYMPTOMS OF CHRONIC FATIGUE SYNDROME
Persistent fatigue not due to ongoing exertion, and not relieved by rest. Fatigue is of a new onset, and greatly reduces activities. Unrefreshing sleep, going to sleep or remaining asleep is hard; altered circadian rhythm (eg awake at night, sleeping during the day). Post-exertional malaise (PEM): physical or mental exertion triggers a state of profoundly worse symptom severity. PEM appears right after the exertion, or hours or days later. This PEM state then lasts for days or even weeks. Cognitive dysfunction (also known as brain fog) which consists of: short-term memory deficits, difficulties in processing information, problems recalling words or names, loss of focus and awareness, confusion and disorientation. Neuropsychological: emotional sensitivity, more susceptible to emotional stress, blunted emotions, emotional lability (emotions are unstable or exaggerated), personality change. Anxiety, panic attacks and depression can appear in chronic fatigue syndrome.
Abdominal: gut pain, irritable bowel, diarrhea. Headaches of a new type. Chronic cough. Chest pain. Irregular heartbeat. Chronic sore throat or recurring sore throat. Tinnitus, dizziness, balance problems. Sensitivities to ordinary sounds, to light, to chaotic or busy environments, to heat or cold. Intolerances to foods, alcohol, odors, chemicals, pollen or drug medications may appear. Blurred vision, dry eyes, dry mouth. Muscles: aches, pains, weakness or tingling. Lymph nodes: enlarged or tender in the neck and armpits. Joint pain: moving from one joint to another, without swelling or redness. Sweating or feverishness episodes. Cold hand and feet. Orthostatic intolerance: an upright posture (standing up) creates symptoms such as fatigue, dizziness, nausea, greatly increased heart rate, sweating, lightheadedness, blood pressure drop, and sometimes passing out.

For the complete set of symptoms formally used for chronic fatigue syndrome diagnosis, see the CDC Fukuda 1994 CFS Criteria, the Canadian Consensus ME/CFS Criteria or the nice and simple IOM Criteria.



Ruling Out Other Conditions With Similar Symptoms to ME/CFS
The inherent problem with diagnosing chronic fatigue syndrome by its symptoms is that many of the same symptoms manifest in other diseases and conditions such as: Lyme disease, hypothyroidism, celiac disease, lupus, anemia, hepatitis B or C, and many others. Thus if you have symptoms resembling chronic fatigue syndrome, you and your doctor first need to rule out diseases and conditions with very similar symptoms before a diagnosis of chronic fatigue syndrome can be given with reasonable certainty.

RULING OUT CONDITIONS SIMILAR TO ME/CFS
Condition
Tests and Results Interpretation
Chronic Lyme disease
Chronic Lyme disease is believed by many researchers to be caused by a chronic infection with certain species of Borrelia bacteria. These bacteria are contracted through the bite of infected Ixodes ticks. When Borrelia is first contracted, it often causes a characteristic erythema migrans rash at the bite location. Early symptoms of Lyme disease include: fever, headache, fatigue and depression.

There is contention about whether Borrelia are present in chronic Lyme disease, but a primate study found Borrelia can form a chronic antibiotic-resistant infection.1 And a human study further corroborated this.1

In the US, it is only Borrelia burgdorferi that causes Lyme disease; in Europe and Asia, three Borrelia species are responsible for Lyme: Borrelia burgdorferi, Borrelia garinii and Borrelia afzelii.1
Borrelia ELISA + western Blot: Dr A Martin Lerner uses western blot and ELISA to test for Borrelia burgdorferi IgM and IgG antibodies.1

This combination of ELISA followed by a western blot (also called immunoblot) is the CDC recommended method for diagnosing Lyme disease. Results are considered positive only when both the ELISA and western blot are positive.1

Lyme and ME/CFS differences in symptoms: in Lyme there is often pain and swelling in the large joints, most often the knees; by contrast in ME/CFS there can sometimes be pain in the joints, but this occurs without swelling. Facial palsy can occur in Lyme, but this does not occur in ME/CFS. These differences in symptoms can act as a differential diagnosis, to help distinguish Lyme disease from ME/CFS. Living or working in a Lyme risk area increases the likelihood you may have Lyme. This chart shows the incidence (and thus the risk) of Lyme across US states. This map shows the tick threat in the UK.

Note: although here we are trying to differentiate Lyme disease from ME/CFS, sometimes Lyme disease leads to ME/CFS. So Borrelia is a pathogen that it is thought may sometimes cause ME/CFS.
Hypothyroidism
Hypothyroidism occurs when your thyroid gland does not produce enough of the thyroid hormone thyroxine.
The symptoms of hypothyroidism are quite similar to those of ME/CFS. Hypothyroidism is diagnosed by a blood test which measures the levels of various thyroid hormones.
Celiac disease
Celiac disease is an autoimmune reaction triggered by gluten, damaging the small intestine causing nutrient malabsorption. Celiac symptoms vary widely between patients, but can resemble those of ME/CFS. Info: Celiac Disease Symptoms.
Transglutaminase antibody blood test and an upper endoscopy with biopsy of the duodenum are used to diagnose celiac disease.

Since celiac symptoms greatly improve after removing ALL gluten from the diet, if you feel much better going gluten-free, it hints you might have celiac disease (though gluten sensitive people without celiac disease will also feel better going gluten-free).
Systemic lupus erythematosus
Lupus is an autoimmune diseases that can cause various symptoms such as joint pains, muscle pains, skin rashes, fatigue and brain fog.
Antinuclear antibody test (ANA). Nearly all patients with lupus will have a positive ANA result; but in ME/CFS patients, a positive ANA is no more common than in the general population (3% to 15% of the general population have a positive ANA).1 Though ME/CFS patients who also have autoimmune conditions such as Hashimoto’s thyroiditis are more likely to have a positive ANA. So while not perfect, the ANA test can be a useful tool to help distinguish lupus from ME/CFS.

Up to 50% of SLE patients exhibit a red butterfly rash on the face, which is not found in chronic fatigue syndrome.
Anemia
Anemia is a decrease in the number of red blood cells, or a decrease in the amount of hemoglobin in those cells, resulting in a reduced ability to carry oxygen.
The symptoms of anemia are similar to those of ME/CFS. Anemia can be diagnosed by a full blood count.

More info: How Anemia Is Diagnosed and Treated.
Hepatitis B or C virus infection
Chronic hepatitis B and hepatitis C viral infections can produce symptoms that resemble those of chronic fatigue syndrome.
Hepatitis B virus can be caught from unprotected sex, including anal and oral sex, and from sharing needles to inject drugs. Hepatitis C virus is most commonly caught by sharing of needles to inject drugs, and is sometimes caught from unprotected sex. A doctor or a sexual health clinic can provide testing for hepatitis B and hepatitis C virus.

For more info on diseases that have similar symptoms to ME/CFS, see: AAFP ME/CFS Differential Diagnosis, Dr Myhill's ME/CFS Differential Diagnosis, Diseases similar to ME/CFS and ME Ireland Illnesses very similar to ME.



Causes and Treatments of Chronic Fatigue Syndrome
Once you have ruled out common diseases with similar symptoms, and have settled on a diagnosis of ME/CFS, then next stage is to try to identify the underlying factors (infections, co-infections, toxic exposures, comorbid illnesses such as orthostatic intolerance, allergies, intestinal dysbiosis, leaky gut, etc) that may be causing or contributing to your ME/CFS. ME/CFS patients may have several factors contributing to their symptoms, and in order best treat ME/CFS, these factors need to be identified and addressed. This is ideally performed with the help of a doctor specializing in chronic fatigue syndrome laboratory testing and treatment.

There are many laboratory tests that people with chronic fatigue syndrome might choose to take. In this roadmap to ME/CFS testing and treatment, the suggested tests are grouped into various rounds, with the most important tests placed in the earlier rounds. Tests for causal factors that have a corresponding treatment or cure are prioritized, since the main goal of this roadmap is to guide people with ME/CFS to treatments that may improve their condition and level of health.

After each round of testing, depending on the test results, advice on an appropriate course of action for treatment is given. The suggested treatment plans are those generally employed by leading chronic fatigue syndrome doctors and researchers in the field, and those which are backed up by published studies. There are no hard and fast rules for chronic fatigue syndrome treatment, and you may wish to follow different courses of action to those given here.

ME/CFS is usually triggered by and linked to certain chronic enterovirus infections (coxsackievirus B and echovirus) and certain chronic herpesvirus infections (Epstein-Barr virus, HHV-6 and cytomegalovirus). In the case of antiviral treatment, this depends on which of these viruses you may have as an active infection in your body. ME/CFS is also linked to parvovirus B19, Chlamydia pneumoniae, as well as other microbes. Non-microbial potential causes or contributory factors to ME/CFS include mold toxin (mycotoxin) exposure. The first round of testing detailed below suggests you consider or get tested for all these microbes and contributory factors.



Notes on Pathogen Testing
Most microbes associated with chronic fatigue syndrome are also commonly found in the general population: Epstein-Barr virus, for example, is found in 95% of adults. Most microbes in the body are acquired from infections earlier in life, but once the immune system has them under control, infections become largely inactive, and are then classified as past or latent infections (these can reactivate though during any temporary weakness in the immune system).

ME/CFS patients often have chronic active infections, as indicated by high IgG antibody titers, and these infections may remain chronically active for years or decades. Regular infection disease specialists will often ignore these high IgG titers, which is why going to see an infection disease doctor is usually of little help. Whereas ME/CFS specialists will interpret these high titers as evidence of a chronic active infection, and will then treat with antivirals.

The chronic active viral infections in ME/CFS are likely not the same as regular active viral infections: evidence suggests ME/CFS patients have non-cytolytic intracellular infections in their muscles and intestinal tissues (and also abortive infections according to one theory). These are unusual infections that do not produce new viral particles, and this likely explains why you do not find much virus in the blood in ME/CFS. So these infections cannot be easily tested for by methods which directly detect viral particles in the blood, such as PCR blood tests.

But if you instead test ME/CFS patients for viral infection using antibody tests, these will often produce strong positive results, suggesting the presence of an active infection somewhere in the body tissues. Antibody tests measure the immune response to a virus, rather than detecting the virus itself.

Thus if antibody testing shows you have a chronic active infection with a virus or bacterium that is known to be linked to ME/CFS, then this suggests infection may be the cause or a contributory factor to your ME/CFS. Whereas if the infection is in an inactive state, then it probably is not playing a causal role.

Empirical testing. While it is always better to test for pathogens or health conditions before using treatments, because some tests are expensive, not available in all countries, or might not always be reliable or sensitive enough to detect certain pathogens, you may choose to bypass the test and go straight to treatment (if the treatment well tolerated and safe). This is known as empirical testing: using a treatment itself as a test for a pathogen or health condition. Empirical testing makes the assumption that if you get better on the treatment, you may well have the pathogen or the health condition that the treatment targets.



1st Round Tests: Common Microbial Infections in ME/CFS
The first set of ME/CFS possible causal factors to consider and/or test for is shown in the table below. The various microbial (and other) causal factors are listed in the left hand column, and recommended tests for these causal factors (plus some basic guidance on interpreting the test result) are given in the right hand column of the table.

FIRST ROUND TESTS
Possible Causal Factor
Tests and Results Interpretation
Coxsackievirus B and echovirus (CVB & EV)
These viruses are strongly linked to ME/CFS in many studies.1 There are 6 coxsackievirus B serotypes and 32 different echovirus serotypes. All are part of the enterovirus genus. If you have an active infection with coxsackievirus B or echovirus, this may be causing your ME/CFS.1 2 3 4

Testing for enterovirus presents some difficulties, as in the chronic enterovirus infections found in ME/CFS, there are hardly any viruses in the blood; the virus is found in the tissues, as a non-cytolytic intracellular infection (non-cytolytic enterovirus is thought may be a major causal factor in ME/CFS).1 2

More info on non-cytolytic enterovirus infection in ME/CFS here.

Thus PCR blood tests are insensitive for chronic enterovirus, because very little virus is found in the blood. You need to use antibody tests, which do not try to detect the virus directly, but instead measure the immune system's antibody response to the virus. So even if the virus is in the tissues, an antibody blood test can detect it. But not all antibody tests have the same sensitivity. Dr Chia found the antibody blood test by neutralization to be the most sensitive for chronic enterovirus. Whereas antibody tests by ELISA and IFA are less sensitive, and antibody tests by CFT are insensitive

The prevalence of IgG antibodies to coxsackievirus B ranges from around 7% to 22% of the general population, according to a study in Greece.1

See CVB & EV treatments
Coxsackievirus B and echovirus antibody neutralization test. Dr John Chia found that the only blood test sensitive enough to reliably detect the chronic enterovirus infections in ME/CFS patients is the neutralization antibody test (plaque reduction neutralization test or the similar microneutralization assay). ARUP Lab in Utah, USA offers such microneutralization antibody tests for coxsackievirus B (LabCorp code 816869) and echovirus (LabCorp code ???) which cost around $440 each. These can be ordered through LabCorp.

Antibody titers of 1:320 and higher in the ARUP tests are good indicators of chronic active infection in the tissues, Dr Chia found.1 In the specific case of coxsackievirus B4, Dr Chia uses titers of 1:640 and higher as the diagnostic threshold for active infection.

If you have such an active infection, that could be the cause of your ME/CFS, and you may want to treat it with the appropriate immunomodulators and antivirals (see the 1st Round Treatments section).

As well as the ARUP tests, Dr Chia also uses the echovirus neutralizing antibody test offered by Cambridge Biomedical (LabCorp code 823361) which costs around $390, and is similar to the ARUP echovirus test. ARUP accepts blood serum samples from abroad if arranged by the patient's doctor. Cambridge Biomedical accept samples from abroad.

The Hellenic Pasteur Institute in Greece provide a coxsackievirus B antibody neutralization test for 68 euros, though this test has not been validated by Dr Chia.

Stomach biopsy (immunohistochemistry). This test, which requires a sample of stomach tissue obtained by an endoscope, is the most sensitive for detecting a chronic enteroviral infection, although it will not indicate which particular CVB and EV serotypes you have. You send your stomach tissue sample to Dr Chia's lab which then tests it for enterovirus. The cost is $250 (excluding the endoscopy fees).

PCR blood tests are not very sensitive for chronic enteroviral infections, as enterovirus mostly disappears from the blood after the acute phase is over (the acute phase of an enterovirus infection is a short window that starts just after initial exposure, and lasts for around 10 days). Dr Chia finds blood PCR may detect about 30% of chronic enterovirus infections in ME/CFS patients.

ELISA and IFA (immunofluorescence assay) type antibody blood tests tend not to be sensitive enough to reliably detect chronic enterovirus.

Complement fixation (CFT) type antibody blood tests are useless for detecting enteroviral activity in chronic infections. The CFT is only of value within the acute phase (first 10 days) of an enterovirus infection.

Further info:
Enterovirus Foundation: Tests for Chronic Enteroviral Infections
Epstein-Barr virus (EBV)
There is a high 95% prevalence of Epstein-Barr virus in the adult population, so most people will have this virus in their system, but usually in a latent inactive state. However, if you have an active EBV infection, it is possible this may be contributing to or causing your ME/CFS symptoms.

After mononucleosis (glandular fever), which is mostly caused by EBV, ME/CFS was found as a sequelae in 9% of cases.1 Another study found that at 6, 12 and 24 months after mononucleosis, 13%, 7% and 4% of patients respectively met the criteria for CFS, indicating that post-mononucleosis CFS can clear up over time, to an extent.1

Evidence indicates that some subtypes of ME/CFS may be due to partial reactivation of Epstein-Barr virus.1 2

See EBV treatments
Epstein-Barr virus antibodies. Dr Martin Lerner says ME/CFS patients have an active EBV infection if there are elevated antibody titers in the EBV IgM VCA and/or EBV EA diffuse tests by ELISA.1 2

Prof Jose Montoya says a Quest EBV IgG VCA titer of 1:640 or higher and a Quest EBV IgG EA titer of 1:160 or higher indicates an active EBV infection in ME/CFS.1 Note: the ranges and notation used in these Quest tests have been changed by the Quest, so the given titer figures in bold are now out of date. However, as a rough guide, high titers in these tests are indicative of a chronic active infection in the context of ME/CFS.

Dr Dantini diagnoses active infection in ME/CFS when IgG titers are at least 4 times the average titers healthy people get on the same test.1

Note that:
EA = early antigen
VCA = virus capsid antigen (also denoted by CA)
EBNA = Epstein-Barr nuclear antigen

If you have an active EBV infection, that could be the cause of your chronic fatigue syndrome, and you may want to treat it with the appropriate antivirals (see the 1st Round Treatments section).

Lymphocyte subset panel. If this test shows elevated CD8 T-cells, this can indicate an ongoing viral infection with EBV or cytomegalovirus, which both raise CD8 T-cells.1
Human herpes virus six (HHV-6)
HHV-6 is found in nearly 100% of adults, usually in a latent inactive state. If you have an active HHV-6 infection, this may be contributing to or causing your symptoms, as active HHV-6 is linked to ME/CFS.1 2 3 4 There are two variants of HHV-6: variant A and variant B, often denoted as HHV-6A and HHV-6B. The A variant is more neurotropic (attacks the nervous system). In healthy blood donors seropositive by PCR for HHV-6B, 62% were also seropositive for HHV-6A.1 So both are common. Tests for HHV-6 do not usually distinguish between the two variants.

Dr Daniel Peterson found that 15% of ME/CFS patients have a HHV-6A infection in their cerebrospinal-fluid.1

Dr Kazuhiro Kondo has a theory that partial reactivation of HHV-6 may cause ME/CFS, as well as depression and bipolar disorder.1

See HHV-6 treatments
HHV-6 antibodies. Dr Martin Lerner says titers of 1:160 or higher in both the LabCorp HHV-6 IgM test and the LabCorp HHV-6 IgG indicate an active HHV-6 infection in ME/CFS.1 2

Prof Jose Montoya uses antibody titers of 1:320 or higher in the Quest HHV-6 IgG IFA test to indicate an active HHV-6 infection in ME/CFS.1

Note: the ranges and notation used in some of these LabCorp and Quest tests have been changed by the labs, so the given titer figures in bold are now out of date. However, as a rough guide, high titers in these tests are indicative of a chronic active infection in the context of ME/CFS.

Dr Dantini diagnoses active infection in ME/CFS when IgG titers are at least 4 times the average titers healthy people get on the same test.1

If you have an active HHV-6 infection, that could be the cause of your ME/CFS, and you may want to treat it with the appropriate antivirals (see the 1st Round Treatments section).

Further info:
HHV-6 Foundation: Viral Testing


Cytomegalovirus (CMV)
Cytomegalovirus is found in 50% of adults, usually in a latent inactive state. If you have an active CMV infection, this may be contributing to or causing your ME/CFS symptoms.

See CMV treatments
Cytomegalovirus IgG antibodies. Dr Martin Lerner says that a diagnosis of cytomegalovirus infection is made by examining the CMV IgG antibody titer. Dr Lerner says the IgM titer for CMV is inaccurate and insensitive.1

Dr Dantini diagnoses active infection in ME/CFS when IgG titers are at least 4 times the average titers healthy people get on the same test.1

Antibody IgG tests:
Quest CMV IgG, LabCorp CMV IgG.
Parvovirus B19 (PB19)
Parvovirus B19 is found in 50% of adults, usually in a latent inactive state. If you have an active parvovirus B19 infection, this may be contributing to or causing your symptoms.1 2 3

Parvovirus B19-induced ME/CFS is quite unique, in that you find an active viral infection in the blood (viremia), which you do not find with enterovirus or herpesvirus-associated ME/CFS (where the infection is in the tissues).

See Parvovirus B19 treatments
Parvovirus B19 PCR and IgM antibodies. Dr John Chia diagnoses active infection when the PCR test is positive, or when there are elevated IgM antibodies.1

Prof Montoya uses PCR to diagnose chronic active parvovirus in ME/CFS.1

PCR tests: Quest PCR, LabCorp PCR.
Antibody tests: Quest IgG/IgM, LabCorp IgG/IgM.

Note that chronic fatigue syndrome may arise after an acute parvovirus B19 infection; however, attributing a particular case of ME/CFS to parvovirus may be difficult without a positive parvovirus blood test taken at the onset of fatigue, when the parvovirus infection was still in its acute phase.1
Chlamydia pneumoniae
Chlamydia pneumoniae, an intracellular bacterium (that lives inside human cells), is linked to ME/CFS. 1 This bacterium is found in a latent state in 74% of the adult population, and about 10% of the population have a persistent active infection with this bacterium, according to a study conducted in Israel.1

See Chlamydia pneumoniae treatments
Chlamydia pneumoniae antibodies.

Antibody tests: Quest IgG/IgA/IgM, LabCorp IgG/IgA/IgM.

Dr Dantini diagnoses active infection in ME/CFS when IgG titers at least 4 times the average titers healthy people get on the same test.1
Toxic mold exposure
Molds synthesize toxic substances called mycotoxins, and some mycotoxins can damage the central nervous system, intestines and kidneys. Molds, which are a type of fungus, can grow on many surfaces provided moisture and oxygen are present.

In the home, molds may typically grow where there is high humidity, such as in a bathroom, kitchen or basement. Molds may also grow where there is moisture from slow water leaks, such as from a leaky roof or leaky dishwasher; or where there is condensation, such as around windows. Previously water damaged areas of buildings are also common places to find mold.

Mycotoxins from mold have been linked to the triggering of ME/CFS. A study by Dr Joseph Brewer found the following mycotoxins in ME/CFS patients: ochratoxin A in 83% of patients, macrocyclic trichothecenes in 44%, and aflatoxins in 12% of patients. None of these mycotoxins were found in healthy controls.1

Other biotoxins such as toxic cyanobacteria might be involved in triggering ME/CFS. In the Lake Tahoe 1984 ME/CFS outbreak, a virus brought down hundreds of people with ME/CFS; but the outbreak never really spread further than the Lake Tahoe area, even though the virus itself would almost certainly have spread beyond this locale. A logical explanation is that there was a second factor present at Lake Tahoe, that when combined with the virus, triggered ME/CFS. It just so happens that Lake Tahoe was covered with a toxic cyanobacteria called Microcystis at the time of the outbreak — so that biotoxin may well have been the second causal factor in the outbreak.

See toxic mold exposure treatments
Mycotoxin urine tests: GPL-MycoTOX, RealTime Lab.

Visual contrast sensitivity test (VCS) can be used to diagnose mold illness. This visual test utilizes your eye's ability to detect shades of contrast as a means to gauge exposure to mold toxins.

A free online version of the VCS test, developed by Dr Ritchie Shoemaker and Dr H. Kenneth Hudnell, which takes just a few minutes to complete, can be found here. If your VCS test comes out positive, it suggests you may be exposed to mold toxins (or other biotoxins or neurotoxins such as ciguatoxin), and have a mold-induced illness.

Note that a positive VCS test result may also occur in Lyme disease, Babesia, diabetes, Parkinson's and Alzheimer's. Furthermore, the VCS test may sometimes come out negative even when there is mold exposure.

Examine your home or workplace for mold. Mycotoxins released from mold growths in the home or workplace float in the air, and may be inhaled, leading to ill health or mold-induced illness. Mold growths can be visible, or may be hidden behind walls and domestic appliances. People can become ill from concealed mold growths without knowing the cause (though a moldy, musty smell warns of the presence of mold). Mold growths are often found in water damaged-buildings containing lots of cellulose material like wood, wallpaper, etc.

Dr Joseph Brewer has hypothesized that a mold infection may also be harbored within the body, continually releasing mycotoxins into the body which contribute to ongoing chronic illness. Brewer suggests that the nasal cavities and sinuses are the most likely sites for harboring mold infections,1 and Dr Brewer has had good success in treating patients with antifungal nasal sprays to kill the sinus and nasal mold.1

Chronic inflammatory response syndrome (CIRS) testing. CIRS is the name given by Dr Shoemaker to the chronic illness induced by mycotoxins and other biotoxins, an illness for which he has developed a treatment protocol. Shoemaker has found that 24% of the population have a genotype that make them susceptible to developing CIRS after exposure to biotoxins, because they cannot properly detoxify biotoxins from their body. The HLA DR blood test can determine if you are one of the susceptible 24% who cannot detoxify biotoxins; having such a genetic susceptibility is one of the criteria required for a CIRS diagnosis, with the other required criteria for CIRS detailed on page 4 of this document.

Also useful: Four Ways to Know if You Have Mold Problems



1st Round Treatments
In the light of the results of the first round of tests, the following treatments can be employed. These 1st round treatments are often capable of moving a patient up by one level on the ME/CFS severity scale of severe, moderate, mild and remission. So for example, a severe patient may move up one level to moderate as a result of treatment, which is a valuable improvement. These treatments can sometimes even lead to full remission, but that is rare. More realistically, a one-level improvement is obtained. Typically up to around one third of patients trying these treatments will achieve such a one-level improvement. Unfortunately others may not benefit at all. However, there are many treatments to try in this roadmap, and although one may not work, another might.

Coxsackievirus B and echovirus treatments. If your tests indicate you have an active infection with one or more enteroviruses of the coxsackievirus B or echovirus species, then Dr John Chia has found (via his informal study) that around 30% of people will make major improvements with a Th1/Th2 immunomodulator called oxymatrine.1 Though Dr Chia suggests that patients with autoimmune tendencies should not take oxymatrine, as there is a risk oxymatrine may trigger rheumatoid arthritis — more info here. Oxymatrine is probably best avoided in young children and during pregnancy.1

Dr Chia has formulated his own brand of oxymatrine called Equilibrant, but there is also White Tiger oxymatrine, and Alternative Medicine Solutions oxymatrine, which work with similar efficacy. These are all Chinese herbal supplements that can be bought online without prescription. Oxymatrine treatment begins by taking half a tablet for the first week or two, then slowly increasing up to 2 or 3 tablets twice daily (so 4 or 6 tablets in total daily). See this video interview with Dr Chia at timecode 4:24. No escalation of dose should be done if there is significant increase in symptoms.1

Responders to oxymatrine should see signs of improvement by 4 to 6 weeks, but a few may take more than 3 months.1 Once the full benefits of oxymatrine have manifested, Dr Chia says men can stop taking it after 3 to 6 months (though here he says to take it for 12 months); but women usually have to continue taking oxymatrine, otherwise they relapse and get worse again. Dr Chia says inosine can be taken with oxymatrine in order to augment the effects.1 Dr Chia sometimes adds rifampin (also called rifampicin) 300 mg twice daily for 7 days to further boost the immunomodulatory action of oxymatrine.1 2

More info on oxymatrine:
Dr Chia: Oxymatrine, Oxymatrine, Autoimmunity, ME/CFS and FM, Quixotic: Equilibrant, Invest in ME 2010 conference transcript, oxymatrine effects, immunomodulators info.

Dr Chia often adds the antiviral lamivudine (Epivir) 150 mg twice daily to patients' medications.1 Dr Chia says this well-tolerated drug has anti-enterovirus effects. But note that Chia finds Epivir has no effect against echoviruses EV6 and EV7.1 Dr Chia says 1 in 3 ME/CFS patients respond well to Epivir.1

Dr Chia uses the antiviral tenofovir (Viread) for ME/CFS, but finds that less than one third of his patients respond to this drug (although when it works for a patient, the benefits are significant).1 2 Dr Willian Weir has also had success in treating ME/CFS with tenofovir. Dr Weir found some patients got worse on this drug though.

Dr Chia has also used intravenous interferon alpha therapy for ME/CFS patients with enterovirus infections (cost $18,000); some patients returned to work after this therapy, but unfortunately tended to relapse after around 4 to 14 months,1 although a few patients had remission of symptoms for as long as 2 to 3 years.1 Dr Chia rarely uses interferon now, because he says people cannot tolerate it (see this Dr Chia video at timecode 3:51). More info: Chia's Interferon Therapy. Note that Dr Chia found interferon alpha does not work for ME/CFS linked to coxsackievirus B4.1 Dr Chia says that the positive effects of interferon beta only last for 3 to 6 months.1
Epstein-Barr virus treatments. If your tests indicate you have an active infection with EBV, this may be causing or contributing to your ME/CFS symptoms. Dr Martin Lerner has shown that the antiviral drug valacyclovir (Valtrex) at a dose of 1,000 mg four times daily often improves ME/CFS symptoms, though usually the benefits only begin to become noticeable after around 3.5 months of treatment.

In Dr Lerner's placebo-controlled study on 27 chronic fatigue syndrome patients with EBV infection, the average improvement in ME/CFS symptoms was a 3-point increase on the Energy Index Point Score scale (for example, as a result of antiviral treatment, an average patient may go from level 4 to level 7 on this scale). Most of the improvement occurs within the first year on Valtrex.1 2 3

In non-responders to Valtrex, Dr Lerner would sometimes add cimetidine (500 mg twice daily) or probenecid (500 mg twice daily), which potentiate blood concentrations of this antiviral drug.1

Valacyclovir can cause decreased kidney function or kidney failure, so it is advisable to test kidney function and also advisable to drink lots of water while on this drug. Those who experience side effects from valacyclovir can substitute with famciclovir (Famvir) at the same dosage, as Famvir is usually much better tolerated. Professor Jose Montoya also uses Valtrex for EBV, but finds slightly lower doses are just as effective, and have lower risk of side effects.

More info on Lerner and Montoya's antiviral treatment for ME/CFS given in this post. Dr Lerner theorized that herpesvirus infections in ME/CFS patients are not regular infections, but chronic abortive infections.

Professor Jose Montoya has found valganciclovir (Valcyte) 450 mg twice daily effective when there is an active EBV infection. This drug needs to be taken for 6 month in order to see improvements.1 Valcyte can have serious side effects and thus patients taking it must be medically monitored.

Nexavir (formerly Kutapressin) may have some immunomodulatory activity against EBV.
Human herpesvirus 6 treatments. If your tests indicate you have an active infection with HHV-6, Dr Martin Lerner has shown that the antiviral valganciclovir (Valcyte) 450 mg three times daily is often beneficial.1

In Dr Lerner's study on 142 chronic fatigue syndrome patients with various herpesvirus infections, 75% of patients responded to the appropriate antiviral treatment (Valtrex or Famvir for EBV, and Valcyte for HHV-6 and cytomegalovirus); the average improvement in ME/CFS symptoms was a 2-point increase on the Energy Index Point Score scale (for example, as a result of antiviral treatment, an average patient may go from level 4 to level 6 on this scale). Much of the improvement occurs within the first year on Valcyte, but it takes two years or so for the full benefits to manifest.1 2

Prof Jose Montoya's placebo-controlled trial found valganciclovir (Valcyte) 450 mg twice daily effective when there is active HHV-6 infection.1 Note that Valcyte is potent antiviral drug with potentially serious side effects, and should only be taken under medical supervision. More info: Valcyte for CFS. Valcyte is expensive: the cheapest price is around $7 for one generic 450 mg tablet. Professor Montoya also prescribes the anti-inflammatory colchicine and hydroxychloroquine which treats autoimmunity.

More info on Dr Lerner and Prof Montoya's antiviral treatment in this post. Dr Lerner posits that the herpesvirus infections found in ME/CFS patients are not regular infections, but chronic abortive infections.

Nexavir (formerly Kutapressin) may have some immunomodulatory activity against HHV-6, and this well-tolerated drug is used to treat chronic fatigue syndrome.

The antimalarial drug artesunate may have efficacy against HHV-6.1

Dr Dan Peterson has had success using the antiviral cidofovir (Vistide) for ME/CFS patients with infections from the herpes family viruses HHV-6 and cytomegalovirus. Cidofovir is potent antiviral drug with potentially serious side effects, and should only be taken under medical supervision.1
Cytomegalovirus treatments. If your tests indicate you have an active infection with cytomegalovirus, Dr Martin Lerner has shown that the antiviral valganciclovir (Valcyte) 450 mg three times daily is often beneficial.1 More info in this post. Dr Lerner posits that the herpesvirus infections found in ME/CFS patients are not regular infections, but chronic abortive infections.

Cidofovir (Vistide) is a potent antiviral for cytomegalovirus, and Dr Dan Peterson uses cidofovir for patients with cytomegalovirus or HHV-6 infections.1 The antimalarial drug artesunate may have efficacy against cytomegalovirus.1

Letermovir (Prevymis) is a potent new antiviral for cytomegalovirus, but expensive at around $195 for each 480 mg daily tablet.

Some studies suggest that high dose valacyclovir (Valtrex) or high dose famciclovir (Famvir) are effective for cytomegalovirus, with 2000 mg of Valtrex or Famvir being equivalent to 450 mg of Valcyte in its efficacy against this virus.1
Parvovirus B19 treatments. If your tests indicate your ME/CFS is likely caused by parvovirus B19 and nothing else, then intravenous immunoglobulin (IVIG) treatment may fully cure you.1 2 3 4
More info: IVIG (Immunoglobulins).
Chlamydia pneumoniae treatments. If you have Chlamydia pneumoniae and no other infections, then antibiotic treatment with azithromycin or rifampin may clear this bacterium. Chlamydia pneumoniae may be a treatable cause of chronic fatigue.1 More info: Dr Stratton's CFS protocol, Chlamydia pneumoniae Treatment Protocols.
Toxic mold exposure treatments. If you have been exposed to high amounts of toxic mold in your home or other building, ensure you prevent further exposure. If the mold growth area in your home is less than around 10 square feet, the EPA suggest that in most case you can perform the cleanup yourself, using the guidelines given in this document: Mold Cleanup in Your Home. However, if the mold growth is greater than 10 square feet, and/or there has been a lot of water damage, you may need to employ a mold remediation contractor.

An air purifier can be employed to remove mold spores and mycotoxins from the indoor air (a purifier with a HEPA filter will remove the mold spores; a purifier with an activated carbon filter is required to remove the mycotoxins).

Dr Ritchie C. Shoemaker is an expert in treating mold-induced illness. The illness precipitated by mold from water-damaged buildings Dr Shoemaker calls chronic inflammatory response syndrome (CIRS), and he has developed an 11 step protocol to treat CIRS. The first step removes the source of toxic mold, the next step involves using cholestyramine to detoxify mycotoxins from the body, and the third step uses a BEG nasal spray to eliminate MARCoNS from the nasal and sinus mucous membranes (if tests show MARCoNS are present). In later steps, a no amylose diet may be employed in patients with elevated MMP-9. A clear and easy to read overview of CIRS and its treatment is found here. A list of doctors trained in the Shoemaker protocol is found here.

CIRS induced by mold can be considered a distinct disease from chronic fatigue syndrome, and although the symptoms of these two diseases are similar, CIRS has its own treatment. Thus it is important for you and your doctor to consider whether you may have CIRS rather than ME/CFS, otherwise you may receive the wrong treatment. Some patients may have a combination of CIRS and ME/CFS: CIRS usually involves mold (or other biotoxin) triggers, whereas ME/CFS usually involves viral triggers, but some patients may be exposed to both mold and viruses.

Dr Joseph Brewer hypothesizes that chronic fatigue syndrome patients may harbor chronic mold infections in their sinus cavities, constantly creating mycotoxins. Dr Brewer has developed some anti-fungal nasal spray protocols to treat these sinus mold infections. One nasal spray he uses contains amphotericin B, and another equally effective nasal spray he uses contains itraconazole. Dr Brewer's 2015 paper showed that approximately 60% of his patients with chronic illnesses make a substantial improvement on this nasal spray protocol.1 More info here.

The BEG nasal spray used in the Shoemaker mold protocol, and the anti-fungal nasal spray used by the Brewer mold protocol, can be purchased at Woodland Hills Pharmacy.

Note: some cases of ME/CFS may be due to a combination of the above pathogenic infections (as well as other causal factors). In which case, conceivably, it may be possible to combine the above treatments in order to tackle the various individual infections.

Before undertaking any treatment, however, you should first become familiar with any risks of taking that treatment, and if unsure, run it by a good ME/CFS doctor first.

More info: Antivirals and Antibiotics for Chronic Fatigue Syndrome.



Antiviral Drugs Summary
The following table summarizes the antiviral and immunomodulator drugs detailed above, and the particular viruses that each drug has useful efficacy against in ME/CFS patients:

Antiviral
Viruses Targeted
Valtrex (valacyclovir) EBV VZV HSV-1 HSV-2
Famvir (famciclovir) EBV VZV HSV-1 HSV-2
Valcyte (valganciclovir) EBV HHV-6 CMV VZV HSV-1 HSV-2
Vistide (cidofovir) EBV HHV-6 CMV VZV HSV-1 HSV-2
Falcigo (artesunate) EBV HHV-6 CMV HSV-1
Foscavir (foscarnet) HHV-6 CMV HSV-1 HSV-2
Prevymis (letermovir) CMV
Zostex (brivudine) VZV HSV-1
IVIG PB19
Oxymatrine CVB EV

References: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.

Herpesviruses linked to ME/CFS: Epstein-Barr virus (EBV), human herpes 6 virus (HHV-6), cytomegalovirus (CMV), varicella zoster virus (VZV), herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2).

Enteroviruses linked to ME/CFS: coxsackievirus B (CVB) and echovirus (EV).

Note: although the Merck Manual states acyclovir and its prodrug Valtrex have "minimal activity against CMV," a study suggests high-dose Valtrex does have efficacy against cytomegalovirus (the study found Valtrex 2000 mg x 4 daily has similar efficacy to Valcyte 900 mg x 2 daily for cytomegalovirus; though the study had some limitations).1 And high-dose Famvir has been used to prevent cytomegalovirus infection in organ transplant recipients.1 However, Dr Lerner's study found that although ME/CFS patients with EBV only improved on Valtrex, those with EBV and cytomegalovirus did not (Lerner found such patients require Valcyte).1

A prodrug is a drug that is converted in the body into an active compound. Valtrex (valacyclovir) is the prodrug of Zovirax (acyclovir), meaning that Valtrex converts into acyclovir in the body. Likewise, Famvir (famciclovir) is the prodrug of Denavir (penciclovir), and Valcyte (valganciclovir) is the prodrug of Cytovene (ganciclovir).

Valcyte, cidofovir and foscarnet can sometimes cause serious side effects, so their use must always be monitored by a medical professional.



General Therapies for ME/CFS
As well as specific pathogen-targeted therapies, there are many additional therapies that can be helpful in chronic fatigue syndrome. These include:

Antiviral immunomodulators. These are drugs and supplements which modulate (modify) the functioning of immune system. The immune system has two modes: the Th1 mode (which fights viruses and intracellular bacteria) and the Th2 mode (which fights extracellular bacteria). These two modes are to some extent mutually exclusive, so that if Th2 is active it will suppress Th1, and vice versa, in a seesaw-like way. To fight the viral and intracellular bacterial pathogens linked to ME/CFS requires the Th1 mode.

There is evidence ME/CFS patients may be swung out towards the Th2 mode,1 which will then result in an undesirable suppression of the antiviral Th1 mode. This is the rationale for using immunomodulators such as oxymatrine and inosine, which shift the immune response away from Th2 and back to Th1.

Oxymatrine is a Th2-to-Th1 immunomodulator used to treat enterovirus-associated ME/CFS, and is detailed in the above "Coxsackievirus B and echovirus infection" section.

Inosine is another Th2-to-Th1 immunomodulator (there is also a drug version of inosine called Imunovir, but ME/CFS doctors say Imunovir is no more effective than the supplement inosine, which is much cheaper and available without prescription).1 Dr John Chia thinks inosine works by modifying the RNA nucleotide encoding of enteroviruses such that the immune system can better identify and fight them. He says some patients taking inosine experience a fever followed by significant improvement because of this. Dr Chia says inosine is best taken in combination with oxymatrine.1 

Low-intensity exercise like walking, tai chi and yoga help shift towards the desirable Th1 mode, whereas higher intensity exercise and longer workout durations shift towards the undesirable Th2 mode.1 ME/CFS patients however must be very careful with exercise, as going past your limit will trigger an episode of post-exertional malaise (PEM).

Rintatolimod (Ampligen) is an immunomodulator drug whose use for ME/CFS was pioneered by Dr Dan Peterson. Anecdotally it has got some ME/CFS patients back to work, and the drug has been shown efficacious in phase III clinical trials.1 It is licensed as an ME/CFS treatment in Argentina, but not at present in the US or Europe. Ampligen is an interferon inducer which works by stimulating the intracellular immune system to fight viral infections located inside human cells. Ampligen is administered by intravenous infusion twice a week. Ampligen is expensive, costing around $15,000 a year (excluding the medical costs of the infusions). More info: Ampligen - MEpedia.

Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) has had mixed results, but can bring benefits (cost is around $25,000 for a course of treatment). Dr Chia finds 20% or so of his ME/CFS patients respond to IVIG.1 He says for ME/CFS patients with severe pain, the pain will go away within 24 hours of an IVIG infusion (see this video at timecode 3:33). Dr Chia says low-dose IVIG is often more effective than high-dose.1 A study found ME/CFS patients with low CD4 counts before treatment are more likely to do well on IVIG.1 2 More info: IVIG - MEpedia, IVIG and ME/CFS.

Azithromycin is an antibiotic that acts as an immunomodulator and can lessen ME/CFS symptoms.1 Azithromycin augments virus-induced interferon beta via its effects on MDA5.1

More info about the immunomodulators used in chronic fatigue syndrome is found here.
Rituximab (Rituxan) is an anti-autoimmunity drug which depletes B-cells in the blood, thereby reducing the autoantibodies that are made by B-cells and which can attack crucial structures in the body. Two phase II clinical trials of rituximab for ME/CFS showed that around two-thirds of patients derived benefit.1 2 Unfortunately a larger phase III clinical trial found rituximab has no benefit for ME/CFS, which now casts doubt on rituximab as an ME/CFS treatment (except perhaps in certain subsets).1 2

Rituximab treatment for chronic fatigue syndrome patients is available at the Open Medicine Institute, California ($50,000) and Kolibri Medical, Stavanger, Norway ($15,000). More info about Kolibri here. Kolibri report that rituximab treatment cures ⅓ of ME/CFS patients, makes an improvement in another ⅓ of patients, and has no effect in the final ⅓ of patients.1

More info: Rituximab - MEpedia.
Low-dose naltrexone (LDN). The drug naltrexone at a low dose of 3 to 4.5 mg daily, taken before bed, can have positive effects for ME/CFS as well as various autoimmune and neurodegenerative diseases. Dr Chia finds LDN helps 10% to 20% of ME/CFS patients, but for those it helps, he says it does so very significantly.1 2 LDN seems to help most fibromyalgia patients.1 LDN is cheap, costing $6 per month.

LDN has mutiple effects in the body: it blocks the mu-, delta- and kappa-opioid receptors briefly (which is thought to up-regulate endorphins), it increases levels of met-enkephalin and its receptor, blocks TLR-4 on microglia, and LDN is believed to increase natural killer cell function (NK function is often low in ME/CFS patients). Note: it is possible that vitamin D3 may be essential for LDN to work properly, so it may be good idea to take vitamin D3 5,000 to 10,000 IU with LDN — see here.

More info on LDN: LDN for Chronic Fatigue Syndrome, LDN Overview, Low dose naltrexone - MEpedia.
Vitamin B12 injections or B12 sublingual tablets. Many ME/CFS patients find that high dose vitamin B12 substantially reduces their cognitive dysfunction (brain fog) symptoms. The recommended forms of vitamin B12 are: methylcobalamin or hydroxocobalamin. One study found that ME/CFS patients taking methylcobalamin responded better than those taking hydroxocobalamin.1 Injectable vitamin B12 doses are around 1000 mcg three times a week; if taken sublingually instead, the dose is 5000 mcg daily. Improvements in symptoms usually appear after a few weeks of taking B12. Further reading: Rationale for using vitamin B12 in CFS, Methylation, B12, Glutathione, Chelation.
Methylation protocol. Dr Rich Van Konynenburg believed that insufficient methylation is a factor behind chronic fatigue syndrome, and recommends boosting methylation using a supplement regimen based on the treatment program developed by Dr Amy Yasko for autism.

The methylation protocol involves taking the following supplements daily: vitamin B12 hydroxocobalamin 2000 mcg sublingual, L-5-MTHF 200 mcg, folinic acid 200 mcg, lecithin 1200 mg, and a multivitamin/multimineral tablet. Full details here: Revised Simplified Methylation Protocol (this is the last revision Rich made to his protocol before his untimely death in 2012).

Rich's study on 30 ME/CFS patients found that 27% of them achieved major improvements from methylation after three months.1 Patients found it took an average of 5 to 6 weeks before the protocol started to work. Some patients find this protocol does not work until they switch to the methylcobalamin form of vitamin B12 rather than using the hydroxocobalamin form.

Prof Carl-Gerhard Gottfries observed that an injection of 1,000 mcg of vitamin B12 given every 4 days plus folic acid 7,000 mcg daily helps ME/CFS.1 Gottfries found B12 methylcobalamin injections give better results than B12 hydroxocobalamin. The Open Medicine Institute are currently running a three-year placebo-controlled, double-blinded study on the efficacy of vitamin B12 plus folate for treating ME/CFS.1

The Health Diagnostics and Research Institute in New Jersey provide a test for methylation status, as do the European Laboratory of Nutrients (see their "amino acids analysis"). However it is not clear whether these tests can predict in advance whether the methylation protocol will work for you or not; so it may be best to forego testing, and just try out the protocol for a few months, and see if you feel better. More info about methylation: Glutathione and the Methylation Cycle, Methylation cycle hypothesis - MEpedia.
Nexavir injections. The injectable drug Nexavir (formerly Kutapressin) is assumed to have anti-inflammatory and immunomodulatory effects, and has demonstrated benefits for ME/CFS. This drug is employed by some ME/CFS doctors, including Dr Cheney, Dr Enlander and Dr De Meirleir. Nexavir treatment protocols vary, but in one study, ME/CFS patients were given one subcutaneous 2 ml injection of Nexavir daily for the first 25 days of treatment; thereafter one injection every two days, for the next 50 days; and thereafter one injection three times a week for the next 105 days. This study reported a 42% remission rate in these patients at the end of this course of Nexavir treatment.1 Each injection costs around $10. A low preservative version of Nexavir called 4ME is used by Dr Kenny De Meirleir. 4ME is available at Kalida (email them for info).

Dr De Meirleir reports that around 70% of his ME/CFS patients experience at least a 20 point increase on the Karnofsky scale as a consequence of taking Nexavir.1 Dr Enlander says that Nexavir helps about 30% of his ME/CFS patients, and when combined with other compounds including vitamin B12 and glutathione injections, Dr Enlander reports Nexavir helps 67% of his chronic fatigue syndrome patients.1
Supplements beneficial for ME/CFS. Acetyl-L-carnitine improves mental fatigue in ME/CFS.1 L-carnitine helps ME/CFS.1 Omega 3 with omega 6 fatty acids (fish oil plus evening primrose oil) improve ME/CFS symptoms.1 VegEPA (EPA-rich essential fatty acids) produces ME/CFS symptom remission and structural brain changes.1 2 Magnesium (either applied transdermally on the skin, or given by injection) can be of benefit in ME/CFS.1 DHEA improves pain, fatigue, anxiety, memory and sexual problems in ME/CFS patients.1 NADH helps ME/CFS.1 Co-enzyme Q10 may increase energy in ME/CFS,1 and 150 mg of Q10 daily has been shown in a clinical trial to improve cognitive function and autonomic dysfunction in ME/CFS.1 Undenatured whey protein may help ME/CFS by boosting intracellular glutathione.1 High cocoa polyphenol rich chocolate may improve ME/CFS symptoms.1

Malic acid taken with magnesium can increase energy in ME/CFS and reduce pain in fibromyalgia.1 2 Pharmaton capsules (which comprise Panax ginseng and B vitamins) significantly improve fatigue in ME/CFS.1 Multi-vitamin and multi-mineral supplements may improve fatigue, sleep disorders, autonomic nervous system symptoms and headaches in ME/CFS.1 Vitamin D supplementation can result in a marked reduction in pain in fibromyalgia.1 Probiotics improve ME/CFS symptoms,1 and reduce anxiety symptoms in ME/CFS.1 D-ribose can significantly improve ME/CFS and fibromyalgia symptoms.1 Melatonin before bed improves fatigue, concentration and motivation in ME/CFS.1 Folinic acid reduces fatigue and pain in ME/CFS.1
Pharmaceuticals beneficial for ME/CFS. Low-dose hydrocortisone (5 to 20 mg daily) reduces fatigue.1 Moclobemide improves brain fog.1 Very low dose amisulpride 50 mg daily reduces fatigue and somatic symptoms, and is well tolerated.1 Methylphenidate (Ritalin) 10 mg twice daily reduces fatigue and improves concetration.1 Several ME/CFS doctors say clonazepam (Klonopin) helps reduce the unpleasant sensory overload problems of ME/CFS, improves sleep and treats anxiety;1 however 32% of patients had severe side effects when trying to stop this drug, although 36% experienced no negative effects when stopping.1

Several ME/CFS doctors find the anticonvulsant drug gabapentin (Neurontin), which is a GABA analog, helps reduce pain, reduces oversensitivity to stimuli, and enhances deep sleep; but on discontinuation this drug can cause significant withdrawal symptoms that can last for months.1 Dr David Bell found amantadine 25 mg to 50 mg twice daily helps ME/CFS, but says higher doses can exacerbate symptoms.1 Several ME/CFS doctors find the stimulant drug modafinil helpful for some ME/CFS patients, to improve improved cognition.1 The drug piracetam (which can also be bought without prescription as a supplement) can treat brain fog symptoms and also improves blood microcirculation and mitochondrial functioning; doses are 800 mg daily or higher.1

More info on various ME/CFS therapies: Maija Haavisto's free abridged ebook "Reviving the Broken Marionette" which lists ME/CFS drugs (full version here), Erica Verrillo and Lauren Gellman's book "CFS Treatment Guide" (1st edition available for free online), Chronic Fatigue Syndrome Treatment – Wikipedia, MEpedia, Treatments for ME/CFS (Cfssufferer's blog), Dr Jacob Teitelbaum's 30 Top Tips for Treating CFS, ME/CFS Medications Database, Dr Jay Goldstein's ME/CFS drug treatments.

Lists of ME/CFS treatments user-rated for effectiveness can be found here, here and here (see page 9).



2nd Round Tests: Common Comorbid Diseases of ME/CFS
This second round of tests and possible causal factors focuses on a few of the comorbid diseases and conditions that are frequently found in ME/CFS patients —€” in many cases, prior to the triggering factor that precipitated the ME/CFS condition (triggering factors such as an enteroviruses, herpesviruses, mold exposure, etc).

Comorbid conditions that are statistically more prevalent in chronic fatigue syndrome or fibromyalgia patients (either prior to ME/CFS onset, or subsequent to onset) include: irritable bowel syndrome, interstitial cystitis and overactive bladder (irritable bladder), chronic pelvic pain syndrome, endometriosis, Raynaud’s disease, atopy (predisposition to allergies), increased allergies, multiple chemical sensitivity, temporomandibular joint disorder, myofascial pain syndrome, attention deficit hyperactivity disorder, depression, generalized anxiety disorder, eating disorders, Hashimoto’s thyroiditis, prolapsed mitral valve, Sjögren's syndrome (sicca syndrome), postural orthostatic tachycardia syndrome (POTS), and neurally mediated hypotension.1 2 3 4

Some of these common comorbid conditions likely play a causal role in the development of ME/CFS (though there is no direct proof of this; all we know at present is that these comorbid conditions are statistically more prevalent in chronic fatigue syndrome patients).

SECOND ROUND TESTS
Possible Causal Factor
Tests and Results Interpretation
Intestinal dysbiosis
Intestinal dysbiosis is where the populations of harmful bacteria or fungi in the large intestine outweigh the populations of beneficial bacteria. People with ME/CFS often have intestinal dysbiosis, and their bowels may harbor some pathogenic microbial species.1 These conditions may be contributing to your ME/CFS symptoms.

See intestinal dysbiosis treatments
Full digestive stool analysis. A stool analysis test will determine whether you have bacterial or fungal overgrowth in your intestines, and will determine whether there are any pathogenic or potentially pathogenic microbes present (potentially pathogenic microbes are those that only cause problems if their populations in the gut become too large).


More info on gut dysbiosis: Fermentation in the gut and CFS
Leaky gut (intestinal permeability)
Leaky gut is an intestinal dysfunction that can allow toxic contents of the small intestine to enter the bloodstream. Leaky gut arises from a dysfunction of the tight junctions in the intestinal wall. Tight junctions are an intelligent barrier that normally precisely controls which substances can pass through the intestinal wall.

Fixing leaky gut improves ME/CFS, and sometimes achieves full remission from ME/CFS. 1 2

Note: 39% of those with diarrhea predominant IBS were found to have leaky gut.1

See leaky gut treatments
The lactulose/mannitol test can detect if you have a leaky gut (intestinal permeability), but this focuses only on the small intestine, and does not test the colon for leakiness.

The polyethylene glycol (PEG) test for leaky gut checks your intestines as a whole for leakiness (the small intestine and the colon).

More info on treating leaky gut in this post.

Irritable bowel syndrome (IBS)
IBS symptoms may include: abdominal pain and bloating; bouts of diarrhoea and/or constipation.

Irritable bowel syndrome is a very common comorbid condition in ME/CFS and fibromyalgia.1 2 One study found 92% of ME/CFS patients, and 77% of fibromyalgia patients had IBS in their lifetime (compared to 18% for healthy controls).1

Note: 39% of those with diarrhea-predominant IBS were found to have leaky gut.1

See IBS treatments
IBS is generally diagnosed by its symptoms; there are no specific tests for IBS. The diagnosis of IBS is performed using either a set of rules called the Manning criteria, or a set of rules called the Rome criteria.

More info: The Manning and Rome Criteria for Irritable Bowel Syndrome.
Small intestine bacterial overgrowth (SIBO)

SIBO is a condition in which abnormally large numbers of bacteria grow in the small intestine. SIBO symptoms are very similar to those of IBS, and include nausea, bloating, vomiting, diarrhea, nutrient malabsorption (thus consequently malnutrition), and weight loss. SIBO is found in 84% of IBS patients, and some hypothesize that SIBO may be the cause of IBS in these cases.1

Eradication of SIBO (if present) has been shown to improve the symptoms of chronic fatigue syndrome.1

See SIBO treatments
Hydrogen breath test. SIBO can be detected using a hydrogen breath test, which involves drinking some lactulose sugar, and measuring the hydrogen or methane gas produced by bacteria in the small intestine as they metabolize this sugar. (These gases enter the bloodstream and are expelled by the lungs, where they are detected in the breath).

A hydrogen breath test can be used as a differential diagnosis to determine whether a patient with IBS-like symptoms actually has IBS or SIBO; these two conditions cannot be distinguished by symptoms alone. 1

D-xylose test. Malabsorption due to SIBO can be detected by the D-xylose test, which involves drinking D-xylose, and measuring levels in the urine and blood; if no D-xylose is found in the urine and blood, it suggests that the small bowel is not absorbing properly.

More info:
Testing for SIBO (a very informative website by Dr Allison Siebecker).
Labs that offer hydrogen breath tests.
Allergies, food intolerance and MCAS
Allergies and food intolerances are commonly found in ME/CFS.1 2 Allergies or food intolerances, especially to gluten or dairy products, may exacerbate ME/CFS symptoms.

Mast cell activation syndrome (MCAS) may also be a contributor to ME/CFS symptoms.1

See Allergy, food intolerance and MCAS treatments
Allergies can be diagnosed by skin prick testing and blood tests. Details here. Note that allergies cannot be diagnosed by hair analysis testing; the hair testing allergy tests sold on the Internet are a scam.

Food intolerances are diagnosed using an elimination diet (exclusion diet). There are no medical tests for food intolerances. Hair analysis tests on the Internet that claim to diagnose food intolerance are a scam. The only way to detect a food intolerance is through monitoring your symptoms while following an elimination diet, introducing suspect foods one by one.

MCAS is hard to diagnose, as its symptoms can vary from one person to the next. Proposed diagnostic criteria for MCAS are detailed here. A list of MCAS symptoms can be found here.
Postural orthostatic tachycardia syndrome (POTS)
There is a high prevalence of POTS in ME/CFS.1 The symptoms of POTS include: postural tachycardia (increased heart rate on standing), headache, abdominal discomfort, dizziness, feeling faint, nausea, fatigue, lightheadedness, sweating, tremor, anxiety, palpitations, exercise intolerance.

POTS is a type of orthostatic intolerance (OI). IO is where an upright posture (standing up) will trigger symptoms.

Note that as well as being a common condition in ME/CFS patients, POTS can also occur on its own without ME/CFS, and in these cases, POTS can sometimes be misdiagnosed as ME/CFS, since POTS even on its own can produce symptoms similar to those of ME/CFS.

POTS is a treatable condition to an extent, so everyone with ME/CFS would be advised to investigate whether they have POTS, as POTS could be contributing to your symptoms.


See POTS treatments
POTS is diagnosed using the tilt table test, or the active standing test, and these have been shown to be comparable in accuracy.1

The active standing test is sometimes called the "poor man's tilt table test", and can easily be performed at home. The active standing test involves measuring the increase in your heart rate that occurs when you stand up from a relaxed lying down position. To perform the active standing test, you simply lie down horizontally and relax for 10 minutes, and at the end of this 10 minute period, measure your heart rate. Then stand up, and after two minutes standing, measure you heart rate again. After 5 minutes standing, measure your heart rate a third time, and after 10 minutes standing, measure it a fourth and final time. If any of your heart rate measurements taken on standing are faster by 27 beats per minute or more than your heart rate while lying down, then you have POTS.

Note that when using a tilt table, the threshold for diagnosis of POTS is an increase in heart rate of 30 beats per minute or more; but Streeten says that for the active standing test, the threshold for diagnosis is best set at 27 beats per minute or more.

Dr Raj suggests that for maximum sensitivity, testing for POTS should be performed in the morning, because POTS symptoms are worse in the morning.1 Note that those aged 12 to 19 years old must have an increase of at least 40 beats per minute in order to be diagnosed with POTS.

Further info on POTS:
dinet.org
www.potsuk.org
www.potsuk.org – Diagnosis
POTSgrrl
POTSgrrl – Treatments
Neurally mediated hypotension (NMH) and orthostatic hypotension (OH)
NMH and OH are conditions in which your blood pressure drops upon standing. In OH the pressure drop is immediate; in NMH the drop occurs after a long period of time standing, or also sometimes after having an unpleasant or upsetting experience.

Symptoms of NMH or OH include: dizziness or light-headedness, feeling that you are going to faint, blurred vision, confusion, weakness, fatigue, nausea. These symptoms appear within a few seconds or minutes of standing up after you've been sitting or lying down, and will disappear if you sit or lie down for a few minutes.1

NMH and OH are types of orthostatic intolerance, where an upright posture (standing up) will trigger symptoms.

Patients with ME/CFS have a high prevalence of neurally mediated hypotension (NMH),1 which is due to a dysfunction of the autonomic nervous system. In some cases ME/CFS patients can experience almost complete resolution of their ME/CFS symptoms once their NMH is treated.1

NMH is also called:
• Neurally mediated syncope
• Neurocardiogenic syncope

OH is also called:
• Postural hypotension

See NMH and OH treatments
Orthostatic hypotension is diagnosed when, on standing from a sitting or lying position, there is a fall in systolic blood pressure of 20 mm Hg or more, and/or a fall in diastolic blood pressure of 10 mm Hg or more within 5 minutes from standing.1 In some people with OH, the drop in blood pressure can take up to 10 minutes to appear. If the occurrence of the blood pressure drop is delayed for more than 3 minutes after standing, this is called delayed orthostatic hypotension. In chronic fatigue syndrome it is the delayed variety of orthostatic hypotension that usually occurs.

These blood pressure measurements can be made with an ordinary home blood pressure meter. Note that a blood pressure reading is expressed as systolic / diastolic, for example: 120 / 80.


Neurally mediated hypotension is diagnosed using a tilt table test that keeps the patient in the upright position for 30 to 45 minutes, to observe whether syncope occurs (syncope is a temporary lost of consciousness due to a drop in blood pressure). More info on the diagnostic technique used for NMH is given here.


More info:
Orthostatic Hypotension
Neurally Mediated Hypotension and its Treatment




2nd Round Treatments
In the light of the results of the second round of tests:

Intestinal dysbiosis treatments. If your digestive stool analysis test indicates bacterial overgrowth and/or the substantial presence of potentially pathogenic gut bacteria such as Aeromonas, Bacillus cereus, Campylobacter jejuni, Citrobacter, Clostridium difficile, pathogenic strains of Escherichia coli, Klebsiella, Morganella morganii, Proteus, Pseudomonas, Salmonella, Shigella, Staphylococcus aureus, Vibrio and Yersinia, then a course of antibiotics, and/or probiotics may help reduce these bacterial populations. Note that some people ME/CFS, typically those who have had this disease for a decade or more, may find their gut is too sensitive to take probiotics.

Dr Sarah Myhill has a good article on gut health in ME/CFS: Fermentation in the gut and CFS.
Leaky gut treatments. If you find you have a leaky gut (intestinal hyperpermeability), this means that potent endotoxins such as lipopolysaccharide (LPS) made by bacteria in your gut may theoretically be escaping into your bloodstream, which may increase inflammation in the body. LPS also reduces the antiviral Th1 immune response, potentially making it harder for your body to fight off viruses.1

Dr Michael Maes demonstrated that anti-inflammatory and antioxidant supplements such as glutamine, N-acetyl-cysteine and zinc, along with a leaky gut diet, can help fix intestinal hyperpermeability, which in turn can lead to clinical improvements in ME/CFS symptoms (though these improvements may take many months to appear).1 Sometimes, complete remission from chronic fatigue syndrome can be obtained by normalizing a leaky gut.1 A comprehensive list of supplements which studies have shown can reduce intestinal permeability are given here.
Irritable bowel syndrome treatments. If you have been diagnosed with irritable bowel syndrome (IBS), note that IBS can be caused by the intestinal protozoan parasites Giardia lamblia and Blastocystis hominis, all of which are treatable. There is also evidence of bacterial infection in IBS (in that the antibiotic rifaximin can put IBS into remission for three months).

For Giardia lamblia, a single dose of the antiprotozoal drug tinidazole is an effective treatment.1 For Blastocystis hominis, a triple drug protocol comprising secnidazole 400 mg x 3 daily, furazolidone 100 mg x 3 daily and nitazoxanide 500 mg x 2 daily, all taken for 10 days, achieves an 82% eradication rate.1 More Blastocystis hominis eradication protocols are detailed here. A two week course of rifaximin, a unique antibiotic which is not absorbed in the intestines (and so remains in the bowels), improves IBS symptoms, and this improvement then lasts for three months.1

For symptomatic relief of IBS, peppermint oil capsules, probiotics, and for IBS with diarhea (IBS-D) the over-the-counter drug loperamide can all help. And the low FODMAPs deit can be effective.

Fecal transplant (bacteriotherapy) may be worth considering: it has a good response rate for treating ME/CFS patients with IBS. According to a study by Dr Thomas Borody in Australia, 58% of ME/CFS patients with IBS given a fecal transplant achieved resolution from their ME/CFS symptoms (of sleep deprivation, lethargy/fatigue). And this resolution in symptoms has been sustained for two decades to date, according to the study. Cost of a fecal transplant is up to $10,000.1 2 3

A new product called Openbiome FMT Capsules G3, which is bacteriotherapy in a convenient and cheap pill form, has been made available (costs just $635). More info here.
Small intestine bacterial overgrowth (SIBO) treatments. If you have been diagnosed with SIBO, there are a number of treatment options, including: the antibiotics rifaximin, neomycin and metronidazole; an elemental diet (to starve the bacteria); and dietary treatments that reduce food sources for the bacteria. See: Treatments Strategy for SIBO. Once the bacterial overgrowth in the small intestine is brought under control by these treatments, it is then necessary to adopt a prevention strategy (such as an ongoing dietary treatment) to stop SIBO from reappearing. Without adopting a prevention strategy, recurrence of SIBO is common.
Allergy and food intolerance treatments. Symptoms resulting from allergies and food intolerances are best controlled by avoiding exposure to the allergens and foods which you have discovered you are sensitive to. Antihistamines can be used to help prevent and treat the symptoms of allergy. For severe allergies, immunotherapy treatment may help desensitize the reaction to the allergens that trigger allergy symptoms.

MCAS treatments. MCAS can be treated to a degree with a combination of H1 and H2 antihistamines, and mast cell stabilizers to reduce mast cell activation:
H1 antihistamines: hydroxyzine, cetirizine
H2 antihistamines: ranitidine, famotidine
Mast cell stabilizers: NasalCrom, GastroCrom, ketotifen
Postural orthostatic tachycardia syndrome (POTS) treatments. If you are diagnosed with POTS, drugs for treating POTS include: beta blockers such as propranolol (most useful in those with elevated norepinephrine), clonidine (Catepres), desmopressin, erythropoietin, fludrocortisone (Florinef), ivabradine (Procoralan), labetalol (Trandate), methyldopa (Aldomet), pyridostigmine (Mestinon), ibuprofen, intravenous saline, SSRI drugs such as escitalopram (Lexapro), SNRI drugs such as venlafaxine (Efexor), bupropion (Wellbutrin), vasoconstrictors such as ergotamine, midodrine, octreotide, ephedrine, pseudoephedrine, yohimbine, theophylline and methylphenidate (Ritalin).

Non-pharmaceutical approaches to treating POTS include: increasing salt or sodium intake (different doctors have recommended anything between 3 and 15 grams of salt daily), along with drinking more water (at least 2 liters a day). Licorice root can be helpful for POTS.

More info on POTS treatments: POTS - What Helps
Neurally mediated hypotension (NMH) and orthostatic hypotension (OH) treatments. If you are diagnosed with NMH or OH, it can be treated by increased salt intake along with increased water intake (at least 2 liters each day); the salt treatment will not be effective unless it is accompanied by the increased water intake,1 vasoconstrictors (see POTS section above for a list), beta blockers such as propranolol, fludrocortisone (Florinef), and licorice root.



3rd Round Tests: Less Common Microbial Infections in ME/CFS
This third round of tests focuses on rarer microbial causes and contributory factors of chronic fatigue syndrome.

THIRD ROUND TESTS
Possible Causal Factor
Tests and Results Interpretation
Varicella zoster virus (VZV)
VZV is the virus which causes chickenpox. Having VZV has been linked to ME/CFS.1 It has been hypothesized that some cases of ME/CFS may be caused by the reactivation of VZV in peripheral nerve ganglia.1

Dr John Chia finds that in a small minority (about 1.5%) of ME/CFS patients, their illness is due to varicella zoster virus, and this form of ME/CFS can easily be treated with antiviral drugs like acyclovir.

See VZV treatments
VZV antibodies.

When varicella zoster virus reactivates, it can cause a shingles rash on the skin. Thus if you have shingles blisters on your skin, it may indicate you have varicella zoster virus reactivation.

Enterovirus infections in their first two months have been shown to cause immunosuppression due to CD8 depletion which can temporarily reactivate VZV.1

So if you develop shingles in the first two months after contracting an enterovirus (enterovirus may initially cause a gastrointestinal or flu-like illness, or herpangina sore throat), the singles may just be due to this immune weakening.
Herpes simplex virus 1 & 2 (HSV)
HSV-1 is found in 58% and HSV-2 is found in 16% of the adult population.

Dr William Pridgen theorizes that fibromyalgia and ME/CFS may be caused by HSV-1 infection in the dorsal root ganglia of the spine (and/or in other nerve ganglia), and treats such infections with a special antiviral protocol which has been validated in clinical trials.

One study found HSV 1 & 2 antibodies more common in chronic fatigue syndrome compared to healthy controls.1

See HSV treatments
HSV 1 & 2 antibodies.
Human herpes virus seven (HHV-7)
HHV-7 is found in 98% of adults, usually in a latent inactive state. HHV-7 has been linked to ME/CFS in several studies, with one study finding active in 53% of ME/CFS patients (either as single infection, or in combination with other active viruses like HHV-6), whereas only 11% of the healthy controls were found to have active HHV-7.1

See HHV-7 treatments
HHV-7 antibodies. Quest provide an IgM and IgG antibody test for HHV-7. Elevated levels of IgG antibodies in this test suggests active infection.
Coxiella burnetii
Coxiella burnetii bacteria cause Q fever, a disease which may be acute or chronic. Most people with acute Q fever recover, but an ME/CFS-like post-Q fever fatigue syndrome occurs in 10% to 25% of acute cases. Note: post-Q fever fatigue syndrome is not the same as chronic Q fever; the latter involves ongoing infection, typically endocarditis heart infection.1

Coxiella burnetii can be treated with antibiotics. The incubation period of Coxiella burnetii is 2 to 3 weeks.1 2 3

See Coxiella burnetii treatments
PCR. During the acute phase of Q fever, PCR can determine if a patient has Q fever (PCR is most sensitive in the first week of illness). However a negative PCR result does not rule out the possibility of having Q fever.

Indirect immunofluorescence assay (IFA) is the gold standard test for acute Q fever.

More about Coxiella burnetii testing here.
Giardia lamblia
Giardia lamblia (also called Giardia intestinalis) is a protozoan parasite that colonizes and replicates in the small intestine, causing giardiasis. One study found that after giardiasis, at least 5% of patients developed ME/CFS symptoms.1

Another study found that giardiasis can trigger ME/CFS which can then last as long as five years; the study also noted that improvements in these ME/CFS symptoms often appear after three years.1

Giardia lamblia also predisposes you to acquiring IBS.1

See Giardia lamblia treatments
Giardia lamblia antigen test.
Mycoplasma species bacteria
60% of ME/CFS patients are found to have blood infections with one or more of the following: Mycoplasma pneumoniae, Mycoplasma fermentans, Mycoplasma hominis and Mycoplasma penetrans. By contrast, such infections are detected in the blood of only 10% of healthy adults. ME/CFS patients infected with more than one mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasmal infections with time.1 2

Mycoplasma is not a cause of ME/CFS, but is a co-infection that may contribute to chronic fatigue syndrome symptoms.

See Mycoplasma treatments
Mycoplasma pneumoniae IgM and IgG antibodies. Dr A Martin Lerner only considers a chronic fatigue syndrome patient to have a persistent Mycoplasma pneumoniae infection if their titer is 1:600 or more (Lerner uses LabCorp for testing).1

Mycoplasma PCR.
Bartonella
Bartonella bacteria can cause fatigue, brain fog and memory loss, and so can worsen your ME/CFS symptoms. Different species of Bartonella cause several diseases in humans: the most common is cat-scratch disease, caused by a Bartonella henselae infection picked up via a scratch or bite from a cat (this infection usually resolves without treatment). Bartonella can also be spread by biting insects.

Bartonella is not a cause of ME/CFS, but is a co-infection that may contribute to chronic fatigue syndrome symptoms.

See Bartonella treatments
Bartonella PCR.

Symptoms of chronic Bartonella infection (bartonellosis) include relapsing low grade fever, blurred vision, photophobia, eye irritation, malaise, decreased appetite, and aches. Bartonella sometimes triggers psychiatric manifestations, such as anger, agitation, panic disorder, and treatment-resistant depression.1 Bartonella's incubation period is usually 3 to 10 days, but can be as long as 20 days.

Bartonella testing has a high false negative rate, but one sign that you have Bartonella is the characteristic striated rash this bacterium can cause on the skin.
Babesia
Babesia is a malaria-like protozoan parasite that causes symptoms including fatigue, mood changes, flu-like symptoms, headache, muscle aches and joint pain. Babesia infects red blood cells causing a disease known as babesiosis. Babesia microti is the most common strain that infects humans. Babesia parasites are transmitted through tick bites.

Babesia is not a cause of ME/CFS, but is a co-infection that may contribute to chronic fatigue syndrome symptoms.

See Babesia treatments
Microscope examination of blood smears. Babesia can be diagnosed by examination under the microscope of stained blood smears, to identify these parasites in the blood.1 However, this microscope method is reliable only in the first two weeks of the infection.1

Babesia antibody test. Babesia can also be diagnosed by an antibody blood test.

Symptoms of Babesia infection (babesiosis) are similar to those of Lyme disease but babesiosis more often starts with a high fever, sweating and chills. However many people infected with Babesia microti feel fine and do not have any symptoms. Babesia's incubation period is 1 to 4 weeks.
Brucella
Brucella bacteria can cause fatigue and ME/CFS-like symptoms. Brucella is transmitted from animals to humans, and the most common route of transmission is from eating raw (unpasteurized) milk or cheese from infected cows, sheep and goats.

Brucella is not a cause of ME/CFS, but is a co-infection that may contribute to chronic fatigue syndrome symptoms.

See Brucella treatments
Brucella antibody test.

Acute symptoms of Brucella infection (brucellosis) include fever, chills, loss of appetite, sweats, weakness, fatigue, joint, muscle and back pain, and headache.

Symptoms of chronic infection include fatigue, recurrent fevers, arthritis, swelling of the heart (endocarditis), spondylitis (inflammation of the vertebrae of the spine, causing back and neck pain). Brucella’s incubation period is 1 to 3 weeks.
West Nile virus
This mosquito-borne virus is found in many countries throughout the world, including the US, Australia, parts of Canada, parts of Europe, but not the UK, Ireland or New Zealand.

Around 1% of the US population have been infected with West Nile virus. Most people experience no symptoms when catching the virus, but about 20% of people develop a fever, headache, vomiting or a rash, and less than 1% develop encephalitis or meningitis, which presents with neck stiffness, confusion or seizure symptoms.

31% of patients with a history of West Nile virus infection reported fatigue that affected their daily activities. Of those with fatigue, 64% met the CDC case definition for CFS.1

So that equates to around 20% of patients with a history of West Nile virus infection developing CFS.

See West Nile virus treatments
Ross River virus
This mosquito-borne virus is only found in parts of Australia, Papua New Guinea, and some South Pacific islands. This virus has been associated with ME/CFS, though most infections of Ross River virus do not produce clinical symptoms and go unnoticed.1 2

See Ross River virus treatments
Ross River virus antibodies.



3rd Round Treatments
In the light of the results of the third round of tests:

Varicella zoster virus treatment. If you have an active infection with varicella zoster virus, then treatment with one of the antiviral drugs acyclovir, valacyclovir or famciclovir may be beneficial.1 Dr John Chia has found that patients with VZV and shingles can dramatically improve within weeks on such antivirals (one bedbound ME/CFS patient who had just two little shingles blisters and returned to work after a few weeks on acyclovir is talked about at timecode 6:58 in this video interview with Dr Chia).

Brivudine
(Zostex) 125 mg once daily for 7 days is a very potent antiviral for varicella zoster virus, but this drug should not be used for longer than 7 days, otherwise there is a risk of liver inflammation (hepatitis).1 The H2 antihistamine cimetidine 200 mg three times daily daily plus 400 mg just before bed can be an effective off-label treatment for varicella zoster virus.1 2
Herpes simplex virus treatment. If you have an active infection with herpes simplex virus I or II, then treatment with one of the antiviral drugs acyclovir, valacyclovir or famciclovir may be beneficial.1 The H2 antihistamine cimetidine may be an effective off-label treatment for herpes simplex virus. 1

Dr William Pridgen's antiviral protocol for herpes simplex combines famciclovir with the COX-2 inhibitor drug celecoxib (which suppresses HSV reactivation 1); in clinical trials this combination proved effective in treating fibromyalgia.1 2 More info on the Pridgen protocol here.
HHV-7 treatment. If you tested positive for an active HHV-7 infection, then note that Valtrex, Famvir and Valcyte may not have any antiviral activity against this virus, whereas cidofovir and foscarnet are potent antivirals for HHV-7. More info here.
Coxiella burnetii treatment. If you have a Coxiella burnetii infection, doxycycline 100 mg daily for 3 months can lead to significant improvements in symptoms.1
Giardia lamblia treatment. If you tested positive for an Giardia lamblia infection (giardiasis), then either a week course of metronidazole, or a single dose of tinidazole or ornidazole, was found to cure the infection in 90% of cases.1 In those with Giardia lamblia infection and ME/CFS or chronic fatigue as their main symptom, treatment of this giardiasis resulted in a complete cure of fatigue in 27% of patients, and a marked improvement in 44% of patients.1
Mycoplasma treatment. If you have a Mycoplasma infection, macrolide and tetracycline classes of antibiotics (such as azithromycin and doxycycline) are effective treatments. For healthy people, two or three week's treatment is required; longer treatment is usually needed in chronic illnesses like ME/CFS.1

Dr A Martin Lerner treats Mycoplasma pneumoniae infection in his ME/CFS patients with intravenous doxycycline 150 mg for six weeks, followed by oral doxycycline 100 to 150 mg twice daily or moxifloxacin 400 mg once daily for three months.1
Bartonella treatment. If you have a Bartonella infection (bartonellosis), it can be treated with antibiotics such as azithromycin, but most cases of cat scratch disease (from Bartonella henselae) resolve without treatment.1
Babesia treatment. If you have a Babesia infection (babesiosis), it is typically treated with a combination of an anti-malarial drug like atovaquone and an antibiotic such as azithromycin for 10 days, but this treatment is extended to at least 6 weeks in people with relapsing disease.1 More info here.
Brucella treatment. If you have a Brucella infection (brucellosis), it can be treated with the antibiotic combination of doxycycline and rifampin for six weeks.1
West Nile virus treatment. There is no specific antiviral treatment for West Nile virus infection.
Ross River virus treatment. There is no specific antiviral treatment for Ross River virus infection.



4th Round Tests: Rarer Causes and Contributory Factors of ME/CFS
This fourth set includes rarer causes or contributory factors of chronic fatigue syndrome.

FOURTH ROUND TESTS
Possible Causal Factor
Tests and Results Interpretation
Pesticide exposure
Chronic exposure to significant amounts of organophosphate pesticides such as malathion have been linked to triggering ME/CFS.1 In one study, farmers using organophosphate-based "sheep dip" in Scotland were found to have rates of ME/CFS four times higher than the national average.1 So this study suggests major exposure to organophosphates increases the risk developing ME/CFS by 4 times.

Pyrethroid pesticides have been linked to chronic fatigue syndrome as well.1 2

Organochlorine pesticides such as DDT and dieldrin have also been linked to ME/CFS,1 2 3 but most organochlorines have been banned for several decades now, with some exceptions such as dicofol which is banned in Europe but still used on cotton and fruit crops in the US, and DDT which is still used for malaria control in Africa and parts of Asia.

See pesticide exposure treatments
Pesticides can enter the body through the mouth, skin, eyes or lungs. Sources of pesticide exposure include garden pesticide sprays used by you or your neighbor, which can be tracked into the house on shoes. Agricultural exposure may occur in rural areas through crop spraying. Pesticide exposure can also occur through treating wood with preservatives, and treating livestock with anti-parastitic preparations, such as sheep dip.

In most countries, pesticide residues on foodstuffs are generally very minimal, and are not of concern.

Organophosphate pesticides are detoxified from the body by an enzyme called paraoxonase; differences in the paraoxonase gene can increase an individual's susceptibility to organophosphates.1 2

Further info: Pesticide Routes of Exposure – PAN UK
Blood transfusion trigger
A study found that 4.5% of ME/CFS patients received a blood transfusion just days before developing a flu-like illness that appeared to trigger their ME/CFS.1

This development of ME/CFS immediately after a blood transfusion may well be caused by the patient acquiring an infection from the transfusion, as blood products may contain viruses such as enteroviruses which are linked to triggering ME/CFS.

Major surgery is also known to sometimes trigger ME/CFS,1 2 and as surgery often involves blood transfusion, this may explain why ME/CFS can appear after such major operations. Surgery also reduces the antiviral Th1 immune response,1 making it harder to combat any viruses caught during surgery.

See blood transfusion trigger treatments

Physical trauma (eg: car accident)
Physical trauma such as a road accident or a fall can precipitate fibromyalgia and ME/CFS,1 particularly if a head or neck injury is sustained (such as whiplash or concussion).

Fibromyalgia or ME/CFS can appear immediately after an accident, or begin to develop over the subsequent months.1 2 One study found fibromyalgia was 13 times more likely to occur following neck injury compared to lower extremity injury.1 However, another study of 264 whiplash patients found no evidence of a greater incidence of fibromyalgia.1

A concussion can precipitate a condition similar to ME/CFS called post-concussion syndrome (PCS). A concussion is a mild traumatic brain injury typically caused by a blow to the head, resulting in short-lived initial symptoms such as loss of consciousness or disturbances in vision (such as "seeing stars"). Most cases of PCS will resolve within six months, but 1 in 10 cases will persist for more than a year.

See physical trauma treatments
Note that hypopituitarism will occur in up to 30% of people who sustain a moderate or severe traumatic brain injury (TBI), and can sometimes occur even in mild TBI cases. Hypopituitarism can have symptoms very close to those of ME/CFS.1 Thus there is a real danger of misdiagnosing such symptoms ME/CFS when the true cause is hypopituitarism.

If a traumatic brain injury is involved, and ME/CFS-like symptoms ensue, testing for hypopituitarism would be advised. The short synacthen test (also called the ACTH stimulation test) is a standard test for hypopituitarism, but this test is not very accurate, and in fact misses 40% of hypopituitarism cases. A more accurate but more complex and risky test for hypopituitarism is the insulin tolerance test.

A trauma to the spine can sometimes cause a syringomyelia to later form in the spinal cord, which may result in ME/CFS-like symptoms. Syringomyelia is a fluid-filled cyst which appears within the spinal cord, and compresses the spinal nerves. Syringomyelia can be treated surgically.

Physical trauma to the spine (or just general wear and tear) can also cause a cervical spinal stenosis to appear, which can produce severe ME/CFS-like symptoms. A stenosis is a narrowing of the space within the spine, which can put pressure on the nerves. Surgical treatment of a stenosis can lead to resolution of ME/CFS symptoms.1

Chiari malformation can also cause ME/CFS-like symptoms. Chiari malformation will not show up on a standard brain MRI. You need an upright, flexion-extension MRI.1 Craniocervical instability and tethered cord can also cause ME/CFS-like symptoms.
Temporomandibular joint (TMJ) dysfunction / jaw misalignment
Temporomandibular joint dysfunction involves inflammation and misalignment of the temporomandibular joint (which connects the jaw bone to the skull). TMJ dysfunction can cause symptoms similar to fibromyalgia and ME/CFS.

Some recovery stories: Recovery from CFS using oral orthotics, Hannah's Story

See TMJ dysfunction treatments
Temporomandibular joint dysfunction can be diagnosed by dental professionals. If you have temporomandibular joint dysfunction (jaw misalignment), or have noticed changes in the shape or alignment of your jaw bone or face, this could be contributing to or underpinning ME/CFS-like or fibromyalgia-like symptoms.

One UK dentist who specializes in diagnosing and treating jaw misalignment causing ME/CFS-like symptoms is Dr M. Amir. Dr Amir says that when jaw misalignment is present, the lateral pterygoid muscle (the muscle on your cheek just in front of your ear) is very painful if you press it.1

One speculative theory of how jaw misalignment might create ME/CFS symptoms centers on the fact that inflammation around the trigeminal or vagus nerves can trigger what is known as the sickness behavior response, and this response has symptoms very similar to those of ME/CFS. Thus possibly, a squeezed trigeminal nerve due to jaw misalignment could conceivably create inflammation in the nerve, thereby triggering ME/CFS-like symptoms.

Another speculative theory of how jaw misalignment might play a role in precipitating fibromyalgia-like symptoms relates to a compound called substance P. Substance P is raised in fibromyalgia patients (but not in ME/CFS patients), and some researchers believe it may play a role in fibromyalgia. Now, raised levels of substance P are also found in TMJ dysfunction patients, with substance P being released into the cerebrospinal fluid when the trigeminal nerve (which runs through the face and jaw) is stimulated. Thus substance P originating from TMJ dysfunction offers a possible explanation of how jaw misalignment might trigger or worsen fibromyalgia symptoms, and may explain how treating TMJ dysfunction can lead to improvements in fibromyalgia.
Jaw bone cavitation infection
Cases of ME/CFS have occasionally been caused or worsened by infections located within the jaw bone (osteomyelitis). Such infections develop inside hollow pockets within the jaw bone called cavitations. Cavitations can be left in the jaw bone after a tooth extraction; and cavitations can be created as a result of osteonecrosis (the death of bone tissue due to poor blood flow to the bone).1

When these jaw bone cavitations also induce facial pain, they are called NICO lesions.

Jaw bone cavitations induce the inflammatory chemokine RANTES, as well as FGF-2, which are both linked to systemic disease.1 2 Increased RANTES has been found in jawbone samples and in the serum of ME/CFS patients, suggesting that RANTES from jaw bone cavitations may play a role in the pathogenesis of ME/CFS.1 More info here.

Here are some stories of ME/CFS improving after treatment of jaw bone cavitations:
My recovery story
Cavitations and root canals
Ian's CFS Website

See jaw bone cavitation infection treatments
Jaw bone infections can be hard to detect, as they often cause only very minimal local symptoms. Yet a local infection within the jaw bone can cause a condition symptomatically identical to ME/CFS.

Sometimes a jaw bone cavitation infection may cause chronic facial pain, but such facial pain is not always present. A simple test for a jaw bone infection is applying pressure with a finger on the gums to the jaw bone beneath; if any area feels painful, this indicates a possible bone infection. Jaw bone infections may cause a sour, bitter taste in the mouth causing bad breath or even gagging.

Panoramic dental X-rays can detect jaw bone cavitations, but are not very reliable, and they also require skilled interpretation by dentists experienced with detecting cavitations (very few dentists have this experience). Ordinary MRI scans or CT scans are not good at detecting jaw bone cavitations, but the MRI STIR scan is accurate and effective in detection. A handheld ultrasound device called the Cavitat scanner is the best and most effective way to detect jaw bone cavitations.

More info on the diagnosis and treatment of jaw bone cavitation infections is given here:
Symptoms and Location of Cavitations
The Appearance of NICO Lesions
Diagnosis and Treatment of Cavitational Lesions

Jaw bone cavitation infections come under the category of focal infections, which are defined as infections localized in a small region of the body. Focal infections within the tonsils may also lead to fatigue symptoms.

UK dental clinics which specialize in diagnosing and treating jaw bone cavitation infections include: Munro-Hall Clinic (Bedford), Tooth Fairy Holistic (Kent).
Sinusitis (sinus infection)
Sinusitis can cause chronic fatigue, and so conceivably sinus infections may worsen chronic fatigue syndrome.1

Patients suffering chronic fatigue (but not proper ME/CFS) due to obstructive sinusitis have reported significant improvements in fatigue after undergoing sinus surgery. The improvements are likely to derive from the easing of sinus inflammation after surgery.

Further info:
Sinus surgery can improve chronic fatigue

See sinusitis treatments
Sinusitis is usually diagnosed from its symptoms (blocked nose or runny nose, and facial pain).

In his studies, Dr Joseph Brewer discovered mycotoxins in ME/CFS patients, and he hypothesizes that these mycotoxins may come from chronic mold infections in this sinuses of ME/CFS patients. See the mold toxin exposure section earlier in this document for more information.

Vaccination trigger
In some cases, ME/CFS appears after vaccination. Dr John Chia has found that around 1.5% of his ME/CFS patients appeared to have their disease triggered by vaccination.1 Dr Charles Shepherd says that the vaccine most commonly linked to triggering ME/CFS is hepatitis B. To a much lesser extent, influenza, BCG, tetanus, meningitis, MMR, polio, hepatitis A and typhoid vaccines have also been anecdotally linked to triggering ME/CFS.1 2

The causal factor in vaccine-triggered disease may be the adjuvant in the vaccine, which Dr Yehuda Shoenfeld says can instigate a condition he has dubbed autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA).1 Adjuvants that can precipitate ASIA include: aluminum hydroxide, squalene and silicone.1 One study examining how ME/CFS or fibromyalgia can arise after hepatitis B vaccination indicated that these diseases can both arise as specific manifestations of ASIA.1

In 2013 the Federal US Court ruled that hepatitis B vaccine caused ME/CFS in one patient, and awarded the patient $1.1 million plus lifetime medical expenses.1

See vaccination trigger treatments

Silicone breast implant leakage
Silicone used for breast and other implants, as well as silicone injections, can in rare cases cause an ME/CFS like illness, as well as autoimmune conditions, if it leaks into the body.1 Silicone is known to affect the immune system (silicone is used as an immune stimulating adjuvant in vaccines for this reason).

See silicone breast implant leakage treatments
Silicone breast implant leakage symptoms can include: pain, swelling, redness and sometimes tingling of the breasts.

More info on silicone illness here.
Ciguatoxin exposure
Ciguatoxin exposure causes the disease of ciguatera, which can later sometimes lead to ME/CFS,1 2 although Dr Shoemaker says ciguatoxin causes CIRS rather than ME/CFS. CIRS is detailed in the mold section.

Ciguatoxin is found in some predatory fish which eat smaller fish that feed on ciguatoxin-producing algae. This toxin cannot be destroyed by cooking.

Ciguatoxin poisoning from fish occurs in tropical and subtropical areas, particularly in the Pacific Ocean, the Indian Ocean, and the Caribbean. All reef fish are capable of causing ciguatera poisoning, but in particular, the species: barracuda, grouper, red snapper, moray eel, amberjack, parrotfish, hogfish, sturgeon, kingfish, coral trout, and sea bass present a risk.

See ciguatoxin exposure treatments
Visual contrast sensitivity test (VCS). This visual test utilizes your eye's ability to detect shades of contrast as a means to gauge your exposure to neurotoxins, including ciguatoxin and mold toxins. A free version of the VCS test, which takes just a few minutes to complete, can be found online here.

Note that a positive VCS test result may also occur in Lyme disease, Babesia, diabetes, Parkinson's and Alzheimer's. Furthermore, the VCS test may sometimes come out negative even when there is exposure.
Radiotherapy or chemotherapy trigger
When undertaken as a cancer treatment, either can lead to chronic fatigue syndrome soon afterwards.1

See radiotherapy or chemotherapy trigger treatments
Ionizing radiation
This can cause ME/CFS-like symptoms (chronic radiation syndrome).1

See ionizing radiation treatments
More info: National CFIDS Foundation — Ionizing Radiation and CFIDS/ME
Corticosteroids in acute viral infection
If immunosuppressive corticosteroids such as prednisone are given during the acute phase of a viral infection, this has been found to precipitate ME/CFS.

Dr John Chia discovered this etiology of acute infection + corticosteroids = ME/CFS by taking detailed medical histories of all his ME/CFS patients. Dr Chia found hundreds of cases where ME/CFS was triggered after the patient had been given corticosteroid drugs inadvertently during acute viral infection.1

See corticosteroids during acute viral infection treatments
Tung oil
Dr Jay Goldstein has noted that many of his ME/CFS patients developed their illness after exposure to tung oil, a solvent used as a wood preservative.1 Dr Carol Jessop has also noted the association between tung oil exposure and ME/CFS.1 Tung oil, also known as China wood oil, is extracted from the seed of the tung tree (Vernicia fordii).

Tung oil is known to potently reactivate Epstein-Barr virus.1 The phorbol ester HHPA in tung oil reactivates EBV. Phorbol esters also inhibit dicer,1 an enzyme which destroys dsRNA, a component of the enterovirus non-cytolytic infections found in ME/CFS.

See tung oil trigger treatments
Meningitis
An episode of meningitis can afterwards lead to chronic fatigue syndrome.1

Viral and bacterial meningitis was found to cause pituitary dysfunction leading to growth hormone deficiency in 29% of cases.1 Low levels of growth hormone can cause symptoms very similar to those of ME/CFS.

See meningitis trigger treatments
It may be a good idea for ME/CFS patients who have had an episode of meningitis or encephalomeningitis to have their growth hormone levels checked. The symptoms of adult growth hormone deficiency are listed here.
Lymph fluid obstruction/stagnation
Osteopath Raymond Perrin has found that ME/CFS patients have improved, and some have even been cured, by a massage technique that he developed for treating ME/CFS, which is designed to circulate lymph fluid. Perrin theorizes that lymph stagnation prevents proper cerebrospinal fluid drainage, thus creating a toxic build-up in the central nervous system that underpins or contributes to ME/CFS.

Further info:
Overview of Perrin's theories here.
Raymond Perrin's website here.

See lymph fluid obstruction or stagnation treatments
Testing for lymph flow obstruction. Raymond Perrin found that most of his ME/CFS patients have a sore and tender spot ("Perrin's point") located 2–3 cm above and 2–3 cm to the left of the left nipple (just under the third rib). This soreness indicates to Perrin that there may be lymph flow stagnation and an irritation of the sympathetic nerves of the thoracic duct.

A study confirmed that 81% ME/CFS patients do indeed have sore and tender spot at Perrin's point (and none of the health controls had this tenderness).1

To test the Perrin point yourself, press your fingers into your skin a spot 2–3 cm above and 2–3 cm to the left of your left nipple; if there is soreness or tenderness at this point, this is a sign your have ME/CFS. More info about Perrin point testing here.



4th Round Treatments
In the light of the results of the fourth round of tests:

Organophosphate, pyrethroid or organochlorine pesticide exposure treatments. If you have been exposed to organophosphate, pyrethroid or organochlorine pesticides, ensure you prevent any further exposure.

Some ME/CFS patients with high blood levels of organochlorines achieved remission from their symptoms after a detoxification regimen comprising choline and ascorbic acid.1 2. Organochlorines are bioaccumulative (build up in the body), so detoxification can be helpful.

However, organophosphate and pyrethroid pesticides are not really bioaccumulative, so a detoxification protocol is not likley to help, except in severe acute exposure.
Blood transfusion-triggered ME/CFS treatments. There are no specific treatments for ME/CFS appearing just after a blood transfusion, but since the ME/CFS may have been caused by aquiring an ME/CFS-associated virus such as herpesvirus or enterovirus from the blood transfusion, it may be a good idea to undertake the viral testing detailed in the 1st round tests section, and address any active infections with the appropriate antiviral or immunomodulatory treatments.
Physical trauma-triggered ME/CFS treatments. If your ME/CFS or fibromyalgia appeared to be triggered by a physical trauma, such as a car accident that involved a head or neck injury, a physical therapy spinal manipulation such as cranial osteopathy or chiropractic may perhaps yield benefits. If the physical trauma led to hypopituitarism, then replacement pituitary hormones may need to be taken.
Temporomandibular joint dysfunction treatments. If you have ME/CFS-like symptoms and you have been diagnosed with temporomandibular joint dysfunction (jaw misalignment), or have noticed changes in the shape or alignment of your jaw or face, consider treating this, because it may help improve your symptoms. Dr M. Amir is a UK Dentist who specializes in diagnosing and treating ME/CFS-like symptoms that may be caused by jaw misalignment or facial asymmetries.
Jaw bone infection treatment. If you suspect you may have a jaw bone cavitation infection, you may want to seek help from a dentist or maxillofacial surgeon who specializes in diagnosis and treatment of jaw bone cavitations.
Sinusitis treatments. Antibiotics may help for bacterial sinusitis, otherwise corticosteroid nasal sprays can help reduce the sinus and nasal inflammation. Avoiding dairy products can improve sinusitis. Surgery to enlarge the sinus openings can be considered when all else fails.
Vaccinaton-triggered ME/CFS treatments. There are no specific treatments for ME/CFS triggered by vaccination, and this type of ME/CFS may respond to the same treatments that are effective for virally-triggered ME/CFS. In particular, even vaccination-triggered ME/CFS patients can have chronic active viral infections, so it may be a good idea to undertake the viral testing detailed in the 1st round tests section, and address any active infections with the appropriate antiviral or immunomodulatory treatments.
Silicone breast implant leakage treatments. Symptoms caused by leakage of silicone from breast implants usually improve on removal of the breast implants.1
Ciguatoxin poisoning treatments. The anti-inflammatory effects of herb Vitex trifolia are useful for treating ciguatera poisoning.1
Radiotherapy or chemotherapy-triggered ME/CFS treatments. Pronounced tiredness and exhaustion are common symptoms during cancer treatment, but in most cases this fatigue clears up one treatment is complete. However, up to 35% who have completed chemotherapy treatment, and who are without known cancer, will experience ongoing persistent tiredness resembling ME/CFS that may last for months or years.

A study found the supplement BioBran (MGN-3) helped ME/CFS due to chemotherapy. It is possible other ME/CFS treatments detailed in this roadmap may be helpful for post-chemotherapy fatigue.
Ionizing radiation-triggered ME/CFS treatments. One study suggests that the ME/CFS-like illness that can appear after ionizing radiation exposure may have share common underlying mechanisms with regular ME/CFS. Thus some of the standard ME/CFS treatments detailed in this roadmap may help.
Treatment of ME/CFS triggered by corticosteroids given during the acute viral infection. There is no specific treatment for ME/CFS triggered by corticosteroid drugs like prednisone inadvertently given during the acute phase of a viral infection. Viral testing detailed in the 1st round tests section can be considered, and any active infections addressed with the appropriate antiviral or immunomodulatory treatments.
Tung oil-triggered ME/CFS treatments. There is no specific treatment for ME/CFS which manifested after tung oil exposure. But since tung oil is known to promote Epstein-Barr virus reactivation, testing for active EBV infectoin in particular, as well as testing for the other viruses tailed in the 1st round tests section, can be considered.
Meningitis or encephalitis-triggered ME/CFS treatments. There is no specific treatment for ME/CFS which manifested after meningitis or encephalitis. Viral testing detailed in the 1st round tests section can be considered, and any active infections addressed with the appropriate antiviral or immunomodulatory treatments.
Lymph flow obstruction treatments. If you think you may have a lymph flow obstruction, you may wish to try the Perrin Technique, which improves lymphatic and cerebrospinal fluid drainage using osteopathic massage and manipulation. Patients also follow a massage and exercise routine at home, involving spinal twists (Perrin twists) which manually activate the thoracic duct (the body's main pump for lymph fluid).



Testing Laboratories
Testing laboratories (pathology labs) where the tests recommended in this document can be obtained are listed below. To search for a test at the labs listed below, click here.

TESTING LABORATORIES
USA
UK / Europe
Canada
LabCorp
Quest Diagnostics
Focus Diagnostics (owned by Quest)
Viracor
ARUP Laboratories

Medical Diagnostic Laboratories
Genova Diagnostics
Life Extension Tests (via LabCorp)
Great Plains Laboratory
Advanced Laboratory Services
DirectLabs

The Doctors Laboratory (TDL)
TDL Manchester
Biolab Medical Unit (Biolab tests can be ordered via Dr Myhill's website; Dr Myhill's interpretation fee must be paid)
Dr MyHill's Test Portfolio
Genova Diagnostics

Red Labs (Belgium)
European Laboratory of Nutrients (Netherlands)
IMD Laboratory (Germany)
MDI Laboratory (Germany)

Neuro Lab
Invivo Clinical
YorkTest Laboratories
MELISA Diagnostics Ltd
Pure Health Clinic

Medichecks (sends samples to TDL)
Blue Horizon Medicals (sends to TDL)
Home Blood Testing (sends to Biolab)
Blood Tests London (uses TDL)
Privatebloodtests.com (Nuffield hospitals)
Privatebloodtests.co.uk (Spire hospitals)
Blood Tests Canada
Australia
New Zealand
Ireland
Centre for Digestive Diseases
MedLab Pathology
Private Blood Tests Ireland



ME/CFS Doctors and Clinics
Some of the world's leading chronic fatigue syndrome doctors and clinics are listed in the table below.

World Map of ME/CFS and CIRS Specialists.

CIRS (mold and biotoxin illness) specialists using the Shoemaker protocol here and here. POTS specialists here, here and here. A US map of Lyme disease specialists here.

More ME/CFS doctors: MEpedia international list of ME/CFS doctors, Co-Cure ME/CFS & Fibromyalgia Good Doctor List (good for local doctors), Chronic Fatigue Syndrome Doctors and Clinics (good for local doctors).


ME/CFS DOCTORS AND CLINICS
USA
Dr John Chia (Torrance, California)Article on Dr ChiaVideo InterviewMEpedia
Dr Chia is an infectious disease specialist with major clinical and research interests in enteroviruses and ME/CFS. He treats enterovirus-associated ME/CFS with the immunomodulator oxymatrine, as well as with antivirals such as Epivir; in some patients he may employ interferon therapy or IVIG. Dr Chia also uses low-dose naltrexone.

Dr Martin Lerner (Oakland, Michigan)Article on Dr LernerMEpedia
Dr Lerner was a leading researcher in ME/CFS associated with herpesvirus and uses antivirals (Valtrex and Valcyte) to treat these infections. He also has particular interest in the cardiac problems and cardiac insufficiency often found in ME/CFS. Dr Lerner died in 2015, after decades of work helping ME/CFS patients.

Professor Jose Montoya (Stanford University, California)Article on Prof MontoyaVideo InterviewMEpedia
Dr Montoya is a leading researcher in ME/CFS associated with herpesviruses HHV-6, EBV and cytomegalovirus. At the Stanford ME/CFS clinic, Dr Montoya and other physicians use the antiviral Valcyte to treat HHV-6 and cytomegalovirus. They also use low-dose naltrexone, colchicine or hydroxychloroquine for autoimmunity, and the immunomodulator rapamycin (sirolimus).1

Dr Daniel Peterson (Sierra Internal Medicine, Nevada)Article on Dr Peterson Video InterviewMEpedia
Dr Peterson is a very experienced ME/CFS doctor and researcher, and has a special interest in natural killer cell functioning in ME/CFS. Dr Peterson uses the antiviral Vistide (cidofovir) in patients with HHV6 and cytomegalovirus infections.

Dr Nancy Klimas (Miami, Florida)Article on Dr KlimasMEpedia
Dr Klimas is a ME/CFS doctor and researcher, and director of the Institute for Neuro Immune Medicine (INIM). Dr Irma Rey and Dr Maria Vera also work at INIM. Dr Klimas has significant experience in using immune modulators for treating ME/CFS.

Dr Andreas M. Kogelnik (Open Medicine Institute, Mountain View, California)Video InterviewMEpedia
Dr Kogelnik is an infectious disease doctor, and an ME/CFS specialist and researcher. He is the founder and director of the Open Medicine Institute. He uses Valcyte on a subset of ME/CFS patients.

Dr David Kaufman (Center for Complex Diseases, Mountain View, California)MEpedia
Dr Kaufman is an HIV/AIDS researcher with clinical experience in HIV and Lyme disease.

Dr Bela Chheda (Center for Complex Diseases, Mountain View, California)
Dr Chheda is an infectious disease specialist.

Dr Charles W. Lapp (Charlotte, North Carolina)Article on Dr LappMEpedia
Dr Lapp runs clinical trials for drugs for ME/CFS and fibromyalgia, and has been using the immunomodulator drug Ampligen for ME/CFS. Dr Lapp retired in January 2018, and Dr Vincent Hillman has taken over the running of this clinic.

Dr Lucinda Bateman (Salt Lake City, Utah)Article on Dr BatemanMEpedia
Dr Bateman is an internist specializing in the treatment of ME/CFS.

Dr Derek Enlander (New York)Video InterviewMEpedia
Dr Enlander uses immune modulators for treating ME/CFS, and the antiviral drug Valcyte.

Dr Daniel Dantini (Ormond Beach, Florida)Article on Dr DantiniDr Dantini's Book The New Fibromyalgia Remedy
Dr Dantini (who once had fibromyalgia himself) has been treating ME/CFS with antivirals since the 1980s. He prefers the antiviral drugs Valtrex (valacyclovir) and Famvir (famciclovir) for herpesvirus-associated ME/CFS, using Valcyte (valganciclovir) and Cytovene (ganciclovir) less, as some patients find these hard to tolerate.

Dr Kent Holtorf (Hortof Medical Group: Los Angeles; Foster City CA; Atlanta; Philadelphia)Old Website
Dr Holtorf focuses on the endocrine system, testing hormones (thyroid, growth hormone, testosterone) and prescribing hormone replacement therapy where necessary. He also addresses mitochondrial and infectious issues.

Dr Garth Nicolson (Huntington Beach, California)MEpedia
Dr Nicolson works with ME/CFS, autoimmune diseases, Gulf War illness, and the infectious causes of autism and neurodegenerative diseases.

Dr Paul Cheney (Asheville, North Carolina)Article on Dr CheneyMEpedia
Dr Cheney is an innovative doctor and researcher using leading edge medicine to treat ME/CFS. Dr Cheney is now semi-retired; he will still do some email and phone consultations.

Dr Alan Weiss (Annapolis, Maryland)
Dr Weiss is an internist who focuses on treatment with supplements, hormone replacement, diet.

Dr Jacob Teitelbaum (Kona, Hawaii)Dr Teitelbaum's BlogMEpedia
Dr Teitelbaum is an internist whose uses his SHINE protocol (Sleep, Hormones, Immunity, Nutrition and Exercise) to treat ME/CFS.

Dr Joseph Garabedian (King of Prussia, Pennsylvania)
Dr Garabedian runs the Garabedian Medical Center, and in his ME/CFS treatment focuses on the HPA axis, mitochondria, infections, neurotoxins, hormone replacement, neutraceuticals.

Dr Ritchie Shoemaker (Pocomoke City, Maryland)MEpedia
Dr Shoemaker specializes in mold- and biotoxin-triggered illnesses. He has retired from seeing patients, but is still available for phone consultations. There also many Shoemaker certified doctors who follow his protocol.

Dr Joseph H. Brewer (Kansas City, Missouri)MEpedia
Dr Brewer is an infectious disease doctor who specializes in ME/CFS, Lyme disease and AIDS. His researches and treats mold infections harbored in the sinuses of ME/CFS patients.

Dr Susan Levine (New, York, New York)Facebook PageMEpedia
Dr Levine employs various treatments including low-dose naltrexone, intravenous immunoglobulin and antivirals.

Dr William Pridgen (Tuscaloosa, Alabama)Article on Pridgen Protocol for Fibromyalgia and ME/CFS
Dr Pridgen is a surgeon with interests in fibromyalgia. He developed an antiviral protocol for fibromyalgia and ME/CFS targeting herpes simplex virus infections in the nerve ganglia, which has successfully completed phase II clinical trials.

Some other chronic fatigue syndrome doctors: Dr Ginevra Liptan (Lake Oswego, Oregon), Dr Benjamin Natelson (New York), Dr Alan Pocinki (Washington DC), Dr Peter Rowe (Baltimore, Maryland), Dr Mark Sivieri (Columbia, Maryland).
UK / Europe
Dr Kenny De Meirleir (Himmunitas, near Brussels, Belgium)Article on Dr MeirleirVideo InterviewMEpedia
Dr Meirleir is a leading ME/CFS doctor and researcher who runs a ME/CFS clinic in Brussels. Dr De Meirleir has a particular interest in the intestinal dysfunction and intestinal dysbiosis of ME/CFS.

Dr Nigel Speight (Durham, UK)MEpedia
Dr Speight is paediatric medical adviser to the ME Association. He treats ME/CFS using drugs like amitriptyline for sleep and pain, melatonin for sleep, methylphenidate (Ritalin) for brain fog.

Dr Sarah Myhill (Powys, Wales, UK)MEpedia
Dr Myhill is a GP with significant experience of ME/CFS, has published research on mitochondrial dysfunction in ME/CFS. On her website, lab tests can be ordered and interpreted. Dr Myhill treats ME/CFS with a Paleolithic diet, vitamin B12 injections, supplements such magnesium and Q10, low-dose amitriptyline for sleep.

Dr William Weir (10 Harley Street, London)MEpedia
Dr Weir is a retired consultant physician with a special interest in ME/CFS.

Dr Amolak Bansal (Epsom & St Helier University Hospitals, UK)MEpedia
Dr Bansal is a consultant immunologist with interests in allergy, autoimmunity, immunodeficiency and ME/CFS. He uses antivirals to treat ME/CFS.

Dr Vinod Patel (Nuneaton, Warwickshire, UK)
Dr Patel uses amitriptyline, gabapentin, melatonin, duloextine and testosterone replacement to treat ME/CFS.

Breakspear Medical Group (Hertfordshire, UK)MEpedia
Breakspear focuses on allergy and environmental illness. For ME/CFS treatment they use antivirals, gammaglobulins for parvovirus, and test and treat rickettsial and bacterial co-infections.

Professor Carmen Scheibenbogen (Charité University Hospital, Berlin, Germany)MEpedia
Professor Scheibenbogen specializes in the role of Epstein-Barr virus in ME/CFS.

Professor Carl-Gerhard Gottfries (Gottfries Clinic, Mölndal, Sweden)Video InterviewMEpedia
Professor Gottfries pioneered the use of the vaccine Staphypan to treat ME/CFS, which showed major benefits in two clinical trials (unfortunately the manufacturer withdrew Staphypan). The Gottfries Clinic uses vitamin B12 and folate to treat ME/CFS.
Canada
Dr Byron Hyde (Nightingale Research Foundation, Ottawa)MEpedia
Dr Hyde uses SPECT scans to demonstrate dysfunction in the brain in ME/CFS patients.

Dr Alison Bested (Toronto, Ontario)MEpedia
Dr Bested is a hematological pathologist specializing in ME/CFS.

Complex Chronic Diseases Program (Vancouver)
They use drugs such as Cymbalta, Fentanyl patch, modafinil; and supplements such D-ribose, Q10, L-carnitine. Also offer acupuncture.
Australia
Australian ME/CFS Good Doctor List

New Zealand
Dr Rosamund Vallings (Howick, Auckland)
Dr Vallings is one of New Zealand’s leading authorities on ME/CFS and has over three decades' experience in treating this disease. Dr Vallings uses the immunomodulator and antiviral Imunovir as one of her treatments for ME/CFS.



Sourcing Pharmaceutical Drugs
Good ME/CFS doctors who provide the appropriate drugs for chronic fatigue syndrome patients are few and far between, and the average primary care doctor is often reluctant to prescribe drugs for off-label or experimental use in ME/CFS. Thus it may be necessary to buy the drugs you need directly from a reliable online pharmacy.

The law in many counties allows 3 months worth of prescription drugs for personal use to be imported from abroad (though these drugs of course cannot be controlled substances). Courtesy of this law, it is possible to easily and legally obtain drugs from online overseas pharmacies, usually without needing to provide a prescription. There are many online overseas pharmacies to choose from, but it is important to find a good one that is trustworthy and reliable. Some reliable prescription-free online pharmacies are listed here.



Sourcing Cheap Supplements
ME/CFS patients often take a range of supplements to help combat the myriad symptoms of this problematic disease. To save on costs, note that there are supplement suppliers like iHerb, Vitacost in the US, and HealthMonthly in the UK, who are well-known for their very low prices. eBay also usually has excellent supplement prices.

Vitamin, herbal and amino acid supplements can be also obtained at very substantial discounts —€” around 5 times cheaper than the regular price —€” if you buy these in bulk powder form, rather than tablet or capsule form. Supplements in powder form can be taken in a smoothie-type drink, or take by swallowing a dose of powder with a little water. A digital weighing scales can be useful for measuring the power dosage (these can be bought for as little as $10).

Some bulk powder supplement suppliers include:

BULK POWDER SUPPLEMENT SUPPLIERS
USA / Canada
UK
Australia / NZ
purebulk.com www.bulksupplements.com www.nutraplanet.com
ca.myprotein.com
www.myprotein.com www.bulkpowders.co.uk
www.bulkpowders.com.au
www.bulkpowders.co.nz