Chronic Fatigue Syndrome

A Roadmap for Testing and Treatment

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

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

Chronic Fatigue Syndrome Diagnosis
There are currently no laboratory tests or biomarkers that can be singularly used to diagnose ME/CFS, 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:

Persistent fatigue not due to ongoing exertion, and not really relieved by rest. The fatigue is of a new onset, and greatly reduces activity levels, compared to before the onset. Cognitive dysfunction (also known as brain fog) which consists of: short-term memory and working memory deficits, problems recalling words or names, loss of focus and awareness, disorientation. Mood disorders which may include: emotional sensitivity, emotional lability (exaggerated emotion) and irritability. Anxiety, panic attacks, and depression are common comorbidities in ME/CFS. Post-exertional malaise: physical or mental exertion triggers a state of profoundly worsened symptoms. This appears right after the exertion, or hours or days later. This state then lasts for days or weeks.
Abdominal: gut pain, irritable bowel, diarrhea. Headaches of a type not previously experienced. Tinnitus, dizziness, balance problems, fainting. Irregular heartbeat. Unrefreshing sleep. Chronic sore throat or recurring sore throat (often from the pathogen that initiated the ME/CFS condition). Chronic cough, dry mouth, dry eyes, blurred vision. Chest pain. Sensitivities to sounds, light, chaotic or busy environments, heat or cold. Allergies or intolerances to foods, alcohol, odors, chemicals, pollen or medications may appear. Muscles: aches, weakness, or tingling sensations in muscles. Lymph nodes: enlarged or painful in the neck and armpits. Joint pain: moving from one joint to another, but without swelling or redness.

For the complete set of symptoms formally used for ME/CFS diagnosis, see the CDC 1994 CFS Criteria, the Canadian Consensus ME/CFS Criteria or the International Consensus ME/CFS Criteria.

Ruling Out Other Conditions
The inherent problem with diagnosing ME/CFS 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 ME/CFS can be given with reasonable certainty.

Tests and Results Interpretation
Lyme disease
Lyme disease is 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 through the bite of an infected tick, it often (but not always) causes a characteristic erythema migrans rash. Early symptoms of Lyme disease include: fever, headache, fatigue and depression.
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 has been shown to be nearly 100% reliable in diagnosing Lyme disease.1 Results are considered positive only when both the ELISA and Western blot are positive.1

More info on testing for Lyme disease: Lyme Testing

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. A chronically stiff neck is common in Lyme, but not common in ME/CFS. These differences in symptoms can act as a differential diagnosis, to help distinguish Lyme disease from ME/CFS.
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, causing damage to the small intestine and nutrient malabsorption. Celiac disease 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 (SLE)
SLE 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 systemic lupus erythematosus (SLE) will have a positive ANA result, but in ME/CFS patients a positive ANA is no more common than in the general population (around 3% to 15% of the general population have a positive ANA).1 Though note that ME/CFS patients who also have autoimmune conditions such as Sjögren's syndrome or 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 SLE from ME/CFS.

Up to 50% of SLE patients exhibit a red butterfly rash on the face, which is not found in ME/CFS.
Anemia is a decrease in the number of red blood cells, or a decrease in the amount of hemoglobin in those cells, either of which results in a reduced ability of the blood 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 on testing for anemia: 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 ME/CFS.
Hepatitis B virus can be caught from unprotected sex, including anal and oral sex, and also from sharing needles to inject street drugs. Hepatitis C virus is most commonly caught by sharing of needles to inject street drugs, and is sometimes caught from unprotected sex. Your doctor or a sexual health clinic can provide testing for hepatitis B and hepatitis C virus infections.

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

Causes and Treatments of ME/CFS
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, toxic exposures, 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 ME/CFS might choose to take. In this roadmap to ME/CFS testing and treatment, the tests suggested are grouped into various rounds, with the most important tests placed in the earlier rounds. After each round of testing, depending on the test results, advice on an appropriate course of action for treatment is given. 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 or cure their condition.

The suggested treatment plans are those generally employed by leading chronic fatigue syndrome doctors and researchers in the field, and which are back 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. These guidelines are an ongoing project which aims to be reasonably comprehensive; but they are not an exhaustive chart of ME/CFS treatments.

Research indicates that treatment-resistant ME/CFS of unproven etiology generally appears to be associated with viruses from the enterovirus genus (specifically: coxsackievirus B and echovirus) and/or to viruses from the herpes family (specifically: human herpes six virus, cytomegalovirus, Epstein-Barr virus). More treatable or curable forms of ME/CFS may be caused by parvovirus B19, Chlamydia pneumoniae, as well as other microbes. Non-microbial causes or contributory factors to ME/CFS include: mold toxin (mycotoxin) exposure and pesticide 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 ME/CFS-associated microbes are very commonly found in the general population: Epstein-Barr virus, for example, is found in 95% of adults. Microbes found in the body are generally acquired from infections earlier in life, but once the immune system has them under control, these infections become largely inactive and dormant; so microbes from past infections normally exist in the body in a latent state (though these pathogens can reactivate and become active if there is weakness in the immune system).

When a test is performed for a microbe, we want to know not only whether you have it in your body, but more importantly, whether it is active or not. In chronic infections, the level of activity of a microbe can be gauged to a certain extent by the amount of IgG antibodies your body produces in response to that microbe. High levels of IgG antibodies tend to suggest an active chronic infection.

Note that the activity of some microbes, notably enteroviruses, cannot be so accurately determined by antibody tests, due to the fact that these microbes can also live inside human cells, as an intracellular infection. The immune system does not readily make antibodies to microbes living inside human cells, so you may have a significant intracellular enterovirus infection, but show relatively low antibody levels when you take a test. Other means of pathogen testing may be employed in these situations. Alternative methods of testing for the presence of pathogens in the body include: PCR (polymerase chain reaction) and viral culture. Viral culture is usually the "gold standard" by which other viral detection methods are judged.

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. 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 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.

Causal Factor
Tests and Results Interpretation
Coxsackievirus B and echovirus (CVB & EV)
These viruses have been strongly linked to ME/CFS. 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

Intracellular infections: enteroviruses can exist in two distinct forms within the body: the normal lytic virus form, which lives in the blood and tissues; and the non-cytolytic virus form, which lives inside human cells, as an intracellular infection. An enterovirus infection begins with a lytic virus, but once in the body, some of these lytic viruses can convert into non-cytolytic viruses. Because non-cytolytic enteroviruses live inside human cells, they are hard to detect. Nevertheless, Dr John Chia and other researchers think non-cytolytic enteroviruses may be a major causal factor in ME/CFS.1 2

The prevalence of coxsackievirus B ranges from around 7% to 22% of the general population, according to a study in Greece.1
Coxsackievirus B and echovirus antibodies. Only ARUP Lab, in Utah, has an enterovirus antibody test sufficiently sensitive enough to detect the low-level "smoldering" chronic enterovirus infections of ME/CFS. These sensitive ARUP Lab tests are: Coxsackievirus B Antibodies, Echovirus Antibodies. Titers of 1:320 and higher in these tests are good indicators of an active infection. ARUP tests can be ordered directly, or ordered through Labcorp.

Stomach biopsy (immunohistochemistry). This test, which requires a sample of stomach tissue obtained by an endoscope, is the most reliable for detecting a chronic enteroviral infection. Dr Chia's lab can process the stomach tissue sample.

PCR testing is not sensitive for chronic enteroviral infections, as these viruses disappear from the blood after the acute phase of the infection is over (the acute phase of an enterovirus infection is a short window that starts just after initial exposure, and last for around 10 days).

Complement fixation test (CFT) is useless for testing 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: Testing for chronic enteroviral infections
Enterovirus-Associated ME/CFS Etiology
Human herpes virus six (HHV-6)
HHV-6 is found in over 90% 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 There are two main variants of HHV-6: variant A and variant B, often denoted as HHV-6A and HHV-6B. Tests for HHV-6 do not usually distinguish between the two variants.

The nasty HHV-6A variant: In the general population, most individuals with HHV-6 have the HHV-6B variant of this virus, but a minority of around 4% have the nasty HHV-6A variant. This nasty HHV-6A variant is more strongly linked to ME/CFS.1 2 So a positive test for HHV-6A may be quite significant if this virus is active.

Dr Kazuhiro Kondo has a theory that partial reactivation of HHV-6 may cause ME/CFS, as well as depression and bipolar disorder.1
HHV-6 antibodies In Professor Jose Montoya's study on ME/CFS patients, when the testing is performed by Focus Diagnostics (owned by Quest), he considers an HHV-6 IgG antibody titer of 1:320 or more to be high.1

Dr Jose Montoya believes that IgG antibody levels are a better guide to the HHV-6 activity in the central nervous system than viral culture from the blood.

Nested PCR for HHV-6A. Regular tests do not distinguish between the HHV-6A and the HHV-6B variants of HHV-6; so if you tested positive for HHV-6, you could have either variant (or both). However, nested PCR tests can specifically determine whether you have the nasty HHV-6A.


Further info:
HHV-6 Foundation: Viral Testing
HHV-6 Foundation: Research Papers
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 is found as a sequelae in 9% of cases.1

New evidence indicates that some subtypes of ME/CFS may be due to partial reactivation of Epstein-Barr virus.1 2
Epstein-Barr virus antibodies In Professor Jose Montoya's study on ME/CFS patients, when the testing is performed by Focus Diagnostics (owned by Quest), he considers an EBV-EA of 1:160 or more and an EBV-VCA 1:640 or more to be high.1

Dr A Martin Lerner says that a positive diagnosis of Epstein-Barr virus infection requires a positive EBV-EA diffuse test and/or a positive EBV-VCA IgM test.1

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

Epstein-Barr virus PCR.

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
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.
Cytomegalovirus IgG antibodies. Dr A Martin Lerner says that a diagnosis of cytomegalovirus infection is made by examining the CMV IgG antibody titer. (Lerner says the IgM titer for CMV is inaccurate and insensitive.) The higher the CMV IgG titer, the greater the viral load.1

Cytomegalovirus PCR.
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 antibodies.

Note that ME/CFS may arise after an acute parvovirus B19 infection; however, attributing a particular case of ME/CFS to parvovirus may be extremely 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 a known cause of 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 Dr Chia has found that Chlamydia pneumoniae is the cause of ME/CFS as much as 10% of his ME/CFS patients.1

Further info:
Stanford University: Chlamydia Pneumoniae
Accurate Chlamydia pneumoniae testing poses significant difficulties and uncertainties. As a result, if you have a negative blood test for Chlamydia pneumoniae, this does not preclude you from having a Chlamydia pneumoniae infection.

More info on Chlamydia pneumoniae testing:
Diagnosis Issues |
Mold toxin exposure
Mold can synthesize toxic substances (mycotoxins) that can damage the central nervous system, intestines and kidneys. These toxins 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

Mold growth can be visible, or it may be hidden behind walls and domestic appliances. People can become ill from hidden mold growths without knowing the cause (though a moldy, musty smell in the environment provides a warning to the possible presence of mold). Usually several species of mold can be found in a mold infestation. Mold species that have very potent mycotoxins include: Stachybotrys, Memnoniella and Acremonium. These three species depend on damp cellulose material (wood, paper, cotton) for nutrition, and thus typically thrive in water damaged-buildings that contain plenty of wood, wallpaper, etc.

Dr Joseph Brewer et al have recently hypothesized that mold may be harbored within the body, and continue to release and/or produce mycotoxins which contribute to ongoing chronic illness. Brewer suggests that sinuses are the most likely candidate as a site for the mold and mycotoxin production.1

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

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.
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

Pyrethroid pesticides have been linked to ME/CFS as well.1

Organochlorine pesticides such as DDT and dieldrin have also been linked to ME/CFS,1 2 3 4 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.
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

1st Round Treatments
In the light of the results of the first round of tests:

Coxsackievirus B and echovirus infection. 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 that around 25% of people will noticeably improve with a herbal immunomodulator called oxymatrine (although Dr Chia suggests that patients with autoimmune tendencies should not take oxymatrine).1 Dr Chia has formulated his own brand of oxymatrine called Equilibrant. More info on oxymatrine: Dr Chia: Oxymatrine, Oxymatrine, Autoimmunity, ME/CFS and FM, Quixotic: Equilibrant. Dr Chia also often adds the antiviral lamivudine (Epivir) to patients' medications.1

Dr Chia has also used interferon therapy for ME/CFS patients with enterovirus infections; many patients went into full remission after this therapy, but unfortunately tended to relapse within around six months, so this is not a permanent cure, but perhaps an encouraging result.1 More info: Chia's Interferon Therapy.
Herpesvirus infection. If your tests indicate you have an active infection with one or more of the three herpesviruses: HHV-6, cytomegalovirus and Epstein-Barr virus, then Dr A. Martin Lerner has recently shown that an anti-herpesvirus treatment comprising the antivirals valganciclovir (Valcyte) and/or valacyclovir (Valtrex) can return ME/CFS patients to a near-normal to normal life, provided you have no active co-infections with pathogens other than these three herpesviruses.1 Professor Jose Montoya also found Valcyte effective when there is an 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 (Valganciclovir) for CFS.

Those who experience side effects from valacyclovir can substitute with famciclovir (Famvir), an antiviral which is usually much better tolerated. Unfortunately, if you have active co-infections with pathogens other than these three herpesviruses, this antiviral treatment on its own has proved ineffectual, according to Dr Lerner. However, it is possible that this anti-herpesvirus treatment, when combined with treatments for the other pathogens, may get results.

The antiviral Nexavir (formerly Kutapressin) displays potent in vitro activity against HHV-6,1 and this well-tolerated drug is used to treat ME/CFS.

The antimalarial drug artesunate has 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 CMV. Cidofovir is potent antiviral drug with potentially serious side effects, and should only be taken under medical supervision. More Info: Peterson Reports Cidofovir Effective in Treating Herpesvirus Infected ME/CFS Patients.

The HIV antiviral drug raltegravir (Isentress) may be effective against the whole family of herpesviruses.1
Epstein-Barr virus infection. If your tests indicate you have an active infection with EBV, this may be causing or contributing to your ME/CFS symptoms. Dr A. Martin Lerner has recently shown that the antiviral drugs valacyclovir (Valtrex) and/or valganciclovir (Valcyte) can be very beneficial in these cases.1 Professor Jose Montoya also found Valcyte effective when there is an active EBV infection.1 Generally, you would first try the safe antivirals Valtrex or Famvir for EBV before you try Valcyte, as Valcyte can have serious side effects and thus patients taking it must be medically monitored.

The antiviral Nexavir (formerly Kutapressin) may have some activity against Epstein-Barr virus.1
Cytomegalovirus infection. The antimalarial drug artesunate has efficacy against cytomegalovirus.1 Cidofovir (Vistide) is effective against cytomegalovirus.
Parvovirus B19 infection. 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, since parvovirus B19 infection is one of the few curable forms of ME/CFS.1 2 More info: IVIG (Immunoglobulins).
Chlamydia pneumoniae infection. If you have Chlamydia pneumoniae and no other infections, then antibiotic treatment with azithromycin or rifampin may clear this bacterium, and may cure fully your ME/CFS. Chlamydia pneumoniae infection is an uncommon but treatable cause of chronic fatigue.1 More info: Dr Stratton's CFS protocol, Chlamydia pneumoniae Treatment Protocols.
Toxic mold exposure. 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: A Brief Guide to Mold, Moisture, and Your Home | EPA. However, if the mold growth is greater than 10 square feet, and/or there has been a lot of water damage, the EPA advise you follow these mold remediation guidelines. Cholestyramine can be used to help detoxify certain mold toxins (such as ochratoxin A, fumonisins and zearalenone) from the body.1 2
Organophosphate, pyrethroid or organochlorine pesticide exposure. 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

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, you should run it by a good ME/CFS doctor first.

More info: Antivirals and Antibiotics for ME/CFS.

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:

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
Nexavir EBV HHV-6
Foscavir (foscarnet) HHV-6 CMV HSV-1 HSV-2
Oxymatrine CVB EV

For treating ME/CFS associated with herpes family viruses, Valcyte is stronger, has a broader antiviral spectrum, and is generally much more efficacious than Valtrex or Famvir.

Notes: Valtrex (valacyclovir) is the prodrug of Zovirax (acyclovir); Famvir (famciclovir) is the prodrug of Denavir (penciclovir); Valcyte (valganciclovir) is the prodrug of Cytovene (ganciclovir). Valganciclovir, cidofovir and foscarnet can sometimes cause serious side effects, so their use must always be monitored by a medical professional. References: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.

Adjunct 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:

Immunomodulators. These are drugs and supplements that modulate the immune system. Many immunomodulators used in ME/CFS shift the immune response from the Th2 mode to the Th1 mode. There is evidence that ME/CFS patients are stuck in the Th2 mode, whereas they should really be in the Th1 mode, because it is the Th1 immune response that fights the viruses and intracellular bacteria linked to ME/CFS.1 These Th2 to Th1 shifting immunomodulator drugs and supplements include: low-dose naltrexone, Imunovir, oxymatrine, Nexavir (formerly Kutapressin), pine cone extract, heparin, and transfer factor.1 2

Note that Th2 to Th1 shifting immunomodulators can make you feel worse for the first few months, but benefits accrue after that initial period. Note also that Dr Paul Cheney believes immunomodulators lose their effect if you do not take regular breaks from them. Regular breaks means an on/off regimen, such as: taking them for 5 days, then stopping for 2 days; and/or taking them for 3 weeks, then stopping for 1 week.

Other immunomodulators used in ME/CFS include: artesunate (often used by Dr Cheney; it inhibits the effects of TNF-alpha 1), azithromycin (an antibiotic that can lessen ME/CFS symptoms 1), etanercept (inhibits the effects of TNF-alpha), Ampligen (a powerful but very expensive immunomodulator drug that modulates interferon and RNase L).

Low-intensity exercises 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
Low-dose naltrexone (LDN). A low-dose naltrexone regimen (3 to 4.5 mg daily, taken before bed) can help halt the progression of various autoimmune and neurodegenerative diseases, including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's, Parkinson's, Crohn's. Many ME/CFS and fibromyalgia patients find LDN beneficial.1 LDN acts as an immunomodulator that stimulates the desired Th1 immune response, and LDN is believed to increase natural killer cell function (NK function is often low in ME/CFS patients). More info: LDN for ME/CFS, LDN Overview.
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, adenosylcobalamin, and hydroxocobalamin. Injectable vitamin B12 doses are around 1000 mcg three times a week; sublingual doses are 5000 mcg taken 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 ME/CFS, 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). A poll found that around 25% of ME/CFS patients achieved major improvements from methylation.

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"). More info about methylation: Glutathione and the Methylation Cycle.
Nexavir injections. The injectable drug Nexavir (formerly Kutapressin) is an antiviral, an anti-inflammatory, and an immunomodulator that has demonstrated overall benefits for ME/CFS, and this drug is often employed by 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 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

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 ME/CFS patients.1
Other drugs and supplements. 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 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 Undenatured whey protein may help ME/CFS by boosting intracellular glutathione.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 miti-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

More info on various ME/CFS therapies: Dr Jay Goldstein's ME/CFS drug treatments, ME/CFS Immune System Treatments at Phoenix Rising, Dr Jacob Teitelbaum's 30 Top Tips for Treating CFS, Dr MyHill Fatigue Treatments, ME/CFS Medications Database, Maija Haavisto's free ebook "Reviving the Broken Marionette" (lists ME/CFS drugs).

2nd Round Tests: Common Comorbid Diseases and Conditions 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 ME/CFS 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 (prostatitis), endometriosis, Raynaud’s disease, multiple chemical sensitivity (increased allergies), 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

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 ME/CFS patients).

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.
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
Leaky gut test (lactulose/mannitol test). The lactulose/mannitol test can detect if you have a leaky gut.

More info: Fixing Leaky Gut Helps ME/CFS.
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
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
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).

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
Labs that offer hydrogen breath tests.
Interstitial cystitis (bladder pain syndrome) and overactive bladder
These two conditions involve an excessive urgency to urinate, and increased frequency of urination. Bladder pain is involved in interstitial cystitis.1 Interstitial cystitis and overactive bladder are common comorbid conditions in fibromyalgia and ME/CFS.1 2 3 Research on cats with interstitial cystitis shows that they may have mild primary adrenal insufficiency.1
Interstitial cystitis (IC) cannot be diagnosed with a simple test. IC is initially diagnosed by exclusion, by ruling out other conditions with similar symptoms, such as infection, bladder stones, bladder cancer, kidney disease, multiple sclerosis, endometriosis, and sexually transmitted diseases. To confirm the initial diagnosis of IC, a fiber-optic tube and camera (cystoscope) is inserted through the urethra and into the bladder (under general anesthetic), to examine the bladder lining. A common sign of IC is numerous red pinpoint spots of blood (glomerulations) on the bladder wall lining.

More info on testing for IC:
Diagnosing and treating interstitial cystitis

Overactive bladder is also initially diagnosed by exclusion, by ruling out other conditions with similar symptoms, such as infection. The diagnosis is confirmed by a procedure called flow cystometry, which involves the insertion of a catheter into the urethra in order to measure the fluid pressure pulses generated by bladder contractions.
Allergies or food intolerances
Allergies and/or 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.
Postural orthostatic tachycardia syndrome
There is a high prevalence postural orthostatic tachycardia syndrome (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.

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 symptoms are similar to those of ME/CFS. Prof Julia Newton believes that a third of all ME/CFS diagnoses could be wrong, because the patient may in fact only have POTS rather than ME/CFS.1 POTS is a treatable condition, so everyone with ME/CFS should investigate whether they have POTS.
POTS is medically diagnosed using the tilt table test. However, you can yourself easily check if you have POTS using a simple home method sometimes called the "poor man's tilt table test," which involves measuring the increase in your heart rate that occurs when you stand up from a lying down position. To perform this "poor man's tilt table 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 professional tilt table, the threshold for diagnosis of POTS is an increase in heart rate of 30 beats per minute or more; but Dr Satish Raj says that for the "poor man's tilt table test," the threshold for diagnosis should be set to 27 or more. Dr Raj also 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:
Orthostatic Intolerance in CFS II – POTS Symptoms – POTS Diagnosis – POTS Treatment – Diagnosis
POTSgrrl – Treatments
Orthostatic hypotension (OH), and
Neurally mediated hypotension (NMH)

OH and NMH 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 OH or NMH 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

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
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.1 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.

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

Intestinal dysbiosis. 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.
Irritable bowel syndrome. If you have been diagnosed with irritable bowel syndrome (IBS), note that IBS can be caused by the intestinal protozoan parasites Giardia lamblia, Blastocystis hominis and Dientamoeba fragilis, 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 antiprotozoal drug tinidazole is an effective treatment.1 For Blastocystis hominis and Dientamoeba fragilis treatment: see the triple drug cocktail (comprising secnidazole, diloxanide furoate and bactrim DS) at the Badbugs website. 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 for three months.1 Fecal transplant (bacteriotherapy) may be worth considering: it has a 58% response rate for treating ME/CFS patients with IBS.1
Small intestine bacterial overgrowth. If you have been diagnosed with small intestine bacterial overgrowth (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.
Leaky gut syndrome. If you find you have a leaky gut (intestinal hyperpermeability), this means that the potent endotoxins such as lipopolysaccharide (LPS) made by bacteria in your gut can escape into your bloodstream. LPS leaking into the bloodstream can create significant system-wide inflammation. LPS also reduces the antiviral Th1 immune response, making it harder for your body to fight off viruses.1 A leaky gut diet can help resolve leaky gut problems. fixing leaky gut in ME/CFS can lead to clinical improvement in symptoms.1 Sometimes, complete remission from ME/CFS can be obtained by normalizing a leaky gut.1
Postural orthostatic tachycardia syndrome (POTS). 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 (DDAVP); 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), drinking more water (up to 2 liters a day), and licorice root. More info on POTS treatments: POTS - What Helps
Neurally mediated hypotension (NMH). If you are diagnosed with NMH, it can be treated by: increased salt intake, increased water intake (2 liters each day), vasoconstrictors (see POTS section above), beta blockers, 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 ME/CFS.

Causal Factor
Tests and Results Interpretation
Giardia lamblia
Giardia lamblia is a protozoan parasite that colonizes and replicates in the small intestine, causing giardiasis. Prior infection with Giardia lamblia predisposes you to acquiring ME/CFS.1 2 3
Giardia lamblia antigen test.
Toxoplasma gondii
This intracellular protozoan parasite, which can be caught from undercooked meat and cat feces, can cause toxoplasmosis, a mild condition that usually clears up on its own. However, Toxoplasma gondii can sometimes cause or contribute to ME/CFS. Toxoplasma gondii does not spread from person to person.

The prevalence of Toxoplasma gondii in humans varies from country to country. It is found in around 11% of people the US, 22% in the UK, and in around 88% in France.
Toxoplasma gondii antibodies.
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

It has been speculated that Mycoplasma species may contribute to ME/CFS symptoms.
Mycoplasma pneumoniae IgM and IgG antibodies. Dr A Martin Lerner only considers a ME/CFS patient to have a persistent Mycoplasma pneumoniae infection if their titer is 1:600 or more (Lerner uses LabCorp for testing).1

Mycoplasma PCR.
Coxiella burnetii
This rare bacterium causes a disease named Q fever, which has ME/CFS-like symptoms. Direct, person-to-person infection occurs rarely, if ever. It can be treated with antibiotics. The incubation period of Coxiella burnetii is 2 to 3 weeks. 1 2
Coxiella burnetii antibodies.
Brucella bacteria can cause ME/CFS-like symptoms. This bacterium can be treated with antibiotics. Brucella’s incubation period is 1 to 3 weeks.
Brucella antibodies.
Human T-lymphotropic virus I & II (HTLV)
Infection with HTLV I or II is a remote possibility to explain a ME/CFS-like condition, though the symptoms of these viruses take decades to appear (it has a very long incubation period), and most people who have these viruses in their body remain healthy, and never manifest any of the diseases HTLV can cause.
HTLV I and II antibody test.

Note that HTLV is a rare infection in the US and Europe. In the UK for example, only 1 person in 3000 carries HTLV I, and the prevalence of HTLV II is even lower. However, in HTLV I endemic areas such as Florida USA, Japan, the Caribbean and South America, the prevalence can be as high as 1 in 100. In the US and Europe HTLV II infection is highest among injecting drug users.

More info: What is HTLV-I, What is HTLV-II.
Ross River virus
This mosquito-borne virus is only found in parts of Australia (and some other countries). This virus has been associated with ME/CFS, though most infections of Ross River virus do not produce clinical symptoms and go unnoticed.
Ross River virus antibodies.
Herpes simplex virus 1 & 2 (HSV)
HSV 1 is found in 58% and HSV 2 is found in 16% of the adult population. It has been suggested that HSV 1 & 2 may play a role in ME/CFS.1
HSV 1 & 2 antibodies.
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 Enterovirus infections in their first two months have been shown to cause immunosuppression due to CD8 depletion which can reactivate VZV.1
VZV antibodies.

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

Giardia lamblia infection. If you tested positive for an Giardia lamblia infection, then either a week course of metronidazole, or a single dose of tinidazole or ornidazole is curative in 90% of cases.1
Mycoplasma infection. 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 weeks treatment is required; longer treatment is usually needed in chronic illness 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
Varicella zoster virus infection. 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
Herpes simplex virus infection. 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 supplement L-lysine (1000 mg twice daily) is also beneficial.1 2

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

Causal Factor
Tests and Results Interpretation
Jaw bone infection
Cases of ME/CFS have occasionally been caused by bone infections (osteomyelitis) inside the jaw bone. Such infections can develop inside jaw bone cavitations (the hollow pockets in the jaw bone left after a tooth extraction).

Further info:
CFS due to osteonecrosis of the jaw
My recovery story
I think I put the puzzle together
Jaw bone infections can be very hard to detect, as they often cause only very minimal local symptoms. Yet a local infection in the jaw bone can cause symptoms identical to ME/CFS.

A simple test for jaw bone infection is applying pressure to jaw bone with a finger; if any area feels painful, this indicates a possible bone infection.

Jaw bone infections will usually not show up on X-rays. However an MRI can detect jaw bone infections. Ultrasound and thermal imaging cameras can also be used to help detect a jaw bone infection. A handheld device called the Cavitat scanner can detect infections hidden within the jaw bone.

Jaw bone 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.

Dr Graeme Munro-Hall and Dr Lilian Munro-Hall are UK dentists that specialize in testing for and treating jaw bone infections.
Sinusitis (sinus infection)
Sinusitis can cause chronic fatigue, and so conceivably sinus infections may worsen ME/CFS.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
Sinusitis is usually diagnosed from its symptoms (blocked nose or runny nose, and facial pain).

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.1

Further info:
Perrin Technique
Testing for lymph flow obstruction. Raymond Perrin found that his ME/CFS patients have a sore and tender spot just under the third rib on their left side. To Perrin, the presence of this soreness indicates a lymph flow stagnation. To test this spot in yourself, press your fingers into a point around 2 cm above and 2 cm to the left of your left nipple; if there is soreness or tenderness at this point, this indicates to Perrin that there is a lymph flow blockage.

Physical trauma (eg: car accident)
Physical trauma such as a road accident or a fall can precipitate fibromyalgia and ME/CFS, particularly if a head or neck injury is sustained (such as whiplash or concussion).
Fibromyalgia and 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, 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 can be treated surgically.
Temporomandibular joint dysfunction (jaw misalignment)
Temporomandibular joint dysfunction (TMJD) is an inflammation and misalignment of the temporomandibular joint (the joint which connects the jaw bone to the skull). TMJD can cause symptoms similar to fibromyalgia and ME/CFS.

More info:
Recovery from CFS using oral orthotics
Temporomandibular joint dysfunction can be diagnosed by dental professionals.

One theory on how jaw misalignment precipitates fibromyalgia-like symptoms relates to a compound called substance P. Substance P is normally raised in fibromyalgia patients (but not in ME/CFS patients) and some believe it may play causal role in fibromyalgia. Now, higher levels of substance P are also found in TMJD patients. Substance P is released into the cerebrospinal fluid when the trigeminal nerve (which runs through the lower jaw) is stimulated. So substance P, originating from TMJD, offers a possible explanation of how TMJD might trigger fibromyalgia-like symptoms, and may explain how treating TMJD can lead to remission from fibromyalgia.
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).

More info on silicone illness here.
Silicone breast implant leakage symptoms can include: pain, swelling, redness and sometimes tingling of the breasts.
In some cases, ME/CFS is triggered by 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

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.1

Ciguatoxin exposure causes ciguatera, which can later sometimes lead to chronic fatigue syndrome.1 2 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.

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.
Ionizing radiation
This can cause ME/CFS-like symptoms (post-radiation syndrome).1
Radiotherapy or chemotherapy
When undertaken as a cancer treatment, either can lead to ME/CFS soon afterwards.1
Food poisoning
Very occasionally, cases of food poisoning can precipitate ME/CFS.
An episode of meningitis can afterwards lead to ME/CFS.1
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.
If corticosteroids (immunosuppressants) are given during the acute phase of a significant respiratory infection, this has been found to sometimes precipitate ME/CFS a few weeks or months later. ME/CFS specialist Dr John Chia discovered this acute infection + corticosteroids = ME/CFS etiology by taking detailed medical histories of all his ME/CFS patients.1

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

Jaw bone infection. If you suspect you may have a focal infection within the jaw bone, you need to seek help from a knowledgeable dentist, but these are hard to find. More info here. Dr Graeme Munro-Hall and Dr Lilian Munro-Hall are UK dentists that specialize in testing for and treating jaw bone infections.
Lymph flow obstruction. 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).
Physical trauma. If you think your ME/CFS or fibromyalgia may be due to a physical trauma, such as a car accident that involved a head or neck injury, physical therapy spinal manipulation such as cranial osteopathy or chiropractic may perhaps yield benefits.
Temporomandibular joint dysfunction. If you have fibromyalgia-like symptoms, and you have been diagnosed with temporomandibular joint dysfunction (jaw misalignment), consider treating this, because it may help improve your fibromyalgia-like symptoms too.
Silicone breast implant leakage. Symptoms caused by leakage of silicone from breast implants usually improve on removal of the breast implants.1
Ciguatoxin poisoning. The anti-inflammatory effects of herb Vitex trifolia are useful for treating ciguatera poisoning.1

Testing Laboratories
Testing laboratories (pathology labs) where the tests recommended in this document can be obtained are listed below.

UK / Europe
ARUP Laboratories
Focus Diagnostics (owned by Quest)
Quest Diagnostics
Medical Diagnostic Laboratories
Genova Diagnostics
Life Extension Tests (via LabCorp)
NeuroScience, Inc
Great Plains Laboratory
Metametrix Clinical Laboratory
Advanced Laboratory Services
Genova Diagnostics
Great Plains Laboratory
Biolab Medical Unit
Neuro Lab
Nutrition Geeks
The Doctors Laboratory (TDL)
TDL Manchester
YorkTest Laboratories
MELISA Diagnostics Ltd
Dr MyHill's Test Portfolio
Pure Health Clinic
Medichecks (sends samples to TDL)
Blue Horizon Medicals (sends to TDL)
Home Blood Testing (sends to Biolab)
Home Blood Test (finger prick tests)
Blood Tests London (uses TDL service) (Nuffield hospitals) (Spire hospitals)

Red Labs (Belgium)
UZ Brussels (Belgium)
InfectoLab (Germany)
European Laboratory of Nutrients (Netherlands)
New Zealand
Diagnostic Insight
Centre for Digestive Diseases
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ME/CFS Doctors and Clinics
Some of the world's leading ME/CFS doctors and clinics are listed in the table below. More info on ME/CFS doctors and clinics here: Co-Cure ME/CFS & fibromyalgia Good Doctor List, Phoenix Rising Forum ME/CFS Doctors, Chronic Fatigue Syndrome Doctors and Clinics.

Dr John Chia (Torrance, California) Article on Dr Chia
Dr Chia is an infectious disease specialist with special interest in enteroviruses (which include coxsackievirus B and echoviruses), and is the leading researcher in enterovirus-associated ME/CFS. He uses the immunomodulator oxymatrine to treat ME/CFS patients.

Dr A Martin Lerner (Oakland, Michigan) Article on Dr Lerner
Dr Lerner is 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.

Professor Jose Montoya (Stanford University, California) Article on Prof Montoya
Dr Montoya is a leading researcher in ME/CFS associated with herpesvirus such as HHV-6, EBV, cytomegalovirus, and uses the powerful antiviral drug Valcyte to treat these herpesviruses where appropriate.

Dr Daniel Peterson (Sierra Internal Medicine, Nevada) Article on Dr Peterson
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 Paul Cheney (Asheville, North Carolina) Article on Dr Cheney
Dr Cheney is an innovative doctor and researcher using leading edge medicine to treat ME/CFS.

Dr Nancy Klimas (Miami, Florida) Article on Dr Klimas
Dr Klimas is a ME/CFS doctor and researcher who runs a ME/CFS clinic. She has significant experience in using immune modulators for treating ME/CFS.

Dr Charles W. Lapp (Charlotte, North Carolina) Article on Dr Lapp
Dr Lapp runs clinical trials for drugs for ME/CFS and fibromyalgia, and has been using the immunomodulator drug Ampligen for ME/CFS.

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

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

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

Dr Andreas M. Kogelnik (Mountain View, California)
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 or a subset of ME/CFS patients.

Dr David Kaufman (Irvine, California)
Dr Kaufman is a HIV/AIDS researcher with clinical experience in HIV and Lyme disease. He is principal director at the Open Medicine Clinic.

Dr Daniel Dantini (Ormond Beach, Florida) Article on Dr Dantini
Dr Dantini uses the antiviral drugs Valtrex (valacyclovir) and Famvir (famciclovir) for herpesviruses in his treatment of ME/CFS where appropriate.

Dr Kent Holtorf (Torrance, California). Hortof Medical Group: Foster City CA, Atlanta, Philadelphia, Salt Lake City
Dr Holtorf's 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 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 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)
Dr Shoemaker specializes in mold-triggered illnesses. He has retired from seeing patients, but is still available for phone consultations.

Dr. Joseph H. Brewer (Kansas City, Missouri)
Dr Brewer is an infectious disease doctor who specializes in ME/CFS, Lyme disease and AIDS.
UK / Europe
Dr Kenny De Meirleir (Himmunitas, near Brussels, Belgium)
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)
Dr Nigel 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)
Dr Myhill is GP with significant experience of CFS, and has a website from which various lab tests can be ordered and interpreted by Dr Myhill.

Breakspear Medical Group (Hertfordshire, UK)
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.
Dr Byron Hyde (Ottawa)
Dr Hyde uses SPECT scans to demonstrate dysfunction in the brain in ME/CFS patients.

Dr Alison Bested (Toronto, Ontario)
Dr Bested is a hematological pathologist specializing in ME/CFS.
Australian ME/CFS Good Doctor List

New Zealand
Dr Rosamund Vallings (Howick, Auckland) Article on Dr Vallings
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 ME/CFS 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. You can search here for online pharmacies that sell the drugs you need.

The law in most 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. The information detailed here may help locate a reliable overseas pharmacy.

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 vitamin, herbal and amino acid supplements can be obtained at substantial discounts —€” around 80% to 90% less than the regular price —€” if you buy these supplements in bulk powder form, rather than tablet or capsule form. Supplements in powder form can taken by swallowing the powder with a little water. It is a good idea to buy a cheap digital weighing scales that weighs down to 1 milligram in order to accurately measure the power dosage (such scales can be obtained for as little as $10).

Some bulk powder supplement suppliers include: