Chronic Fatigue Syndrome
A Roadmap for Testing and Treatment

Chronic fatigue syndrome is a disease marked by constant fatigue, post-exertional malaise (PEM) where your symptoms get worse after physical or mental exertion, brain fog (cognitive impairment), unrefreshing sleep, and other symptoms. This illness is also called myalgic encephalomyelitis, and is abbreviated to ME/CFS.

This roadmap will help you determine: (1) whether you have ME/CFS, and if so: (2) which laboratory tests you can take to identify the infections and other factors that may be underpinning your illness, and: (3) which therapies you can use to tackle these infections/factors to improve your overall health.

The ME/CFS therapies detailed in this roadmap can sometimes produce major improvements in health. If you would like to skip straight to those treatments: the general ME/CFS therapies are found here, and the antiviral treatments here.

A world map of top ME/CFS doctors is here.

Page Index

Chronic Fatigue Syndrome Diagnosis
There are no lab tests or biomarkers that can be used to diagnose chronic fatigue syndrome, so diagnosis is performed on symptoms alone, using a standard set of criteria. ME/CFS involves many symptoms, both physical and cognitive, which typically include the following (patients may not have every symptom):

Persistent fatigue not due to ongoing exertion, and not relieved by rest. The fatigue is of a new onset, and greatly reduces activities.
Unrefreshing sleep, hard to get to sleep or remain asleep; altered circadian rhythm, eg awake at night, sleeping during day.
Post-exertional malaise (PEM): physical or mental exertion triggers a state of profoundly worsened symptoms. PEM may hit right after the exertion, or hours or days later. This PEM state may then last for days or even weeks.
Lack of endurance during physical exertion.
Cognitive impairment (brain fog) consisting of: short-term memory problems, 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.
, panic attacks and depression can appear.
Abdominal: gut pain, irritable bowel, diarrhea.
Headaches of a new type, pattern, or severity.
Chronic sore throat
or recurring sore throat. Chronic cough.
, dizziness, balance problems. 
Sensitivities to sounds, to light, to chaotic or busy environments. .
Intolerances to foods, alcohol, odors, chemicals, pollen or drug medications may appear.
Heat or cold intolerance.
Blurred vision, dry eyes, dry mouth.
Muscles: aches, pains, weakness or tingling.
Lymph nodes: swollen and/or tender.
Joint pain
: moving from one joint to another, but no swelling or redness.
Sweating or feverish episodes.
Cold hand and feet.
Orthostatic intolerance: standing up in an upright posture creates symptoms such as: fatigue, dizziness, nausea, greatly increased heart rate, sweating, lightheadedness, blood pressure drop, and sometimes passing out.

Diagnosing ME/CFS by its symptoms is achieved using a set of diagnostic criteria, such as the simple IOM criteria and the CDC Fukuda criteria, or the more exacting Canadian consensus criteria (CCC) and international consensus criteria (ICC).

If your symptoms satisfy these criteria, then you are diagnosed with ME/CFS. You can check if your symptoms satisfy these ME/CFS criteria by using the symptoms questionnaire on this page.

Though before an ME/CFS diagnosis can be considered, other diseases with similar symptoms must be ruled out (see next section).

Note that ME/CFS can be mild (able to work), moderate (housebound), severe (bedbound most of the day) and very severe (completely bedbound). More details of this ME/CFS scale of severity here.   

Ruling Out Diseases With Similar Symptoms to ME/CFS
Diagnosing ME/CFS by symptoms alone has an inherent problem: similar symptoms are present in other diseases, including hypothyroidism, celiac disease, lupus, anemia, hepatitis B or C and Lyme disease.

Thus if you have symptoms resembling chronic fatigue syndrome, you and your doctor first need to rule out other symptomatically-similar diseases, before an ME/CFS diagnosis can be given with reasonable certainty. The table below details some common diseases with similar symptoms to ME/CFS, and how to test for them. Many of these similar diseases are much more treatable than ME/CFS, so it is important to look into them.

If you have already ruled out these similar diseases, you can skip to the next section, which is about ME/CFS causes and treatments.

An excellent online diagnostic tool to help determine which illness you may have is Symptoma. Just enter all your symptoms (separated by commas), and Symptoma uses AI to suggest diseases matching your symptoms.

Condition Tests and Results Interpretation

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.

Note that high-dose biotin (eg 5,000 mcg) can interfere with thyroid lab tests.
Thyroid hormones blood test. Hypothyroidism is diagnosed by a blood test which measures levels of thyroid hormones. The standard test measures two hormones: thyroid-stimulating hormone (TSH) and thyroxine (T4). High TSH and low T4 suggests an underactive thyroid.1

Note however that even if you are not clinically hypothyroid, around 16% of ME/CFS patients suffer from a subclinical hypothyroidism called low T3 syndrome, where triiodothyronine (T3) is low even though TSH is normal. See the low T3 syndrome section for details.
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 disease 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 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.
Chronic Inflammatory Response Syndrome

Chronic inflammatory response syndrome (CIRS) is the name given by Dr Ritchie Shoemaker to the chronic illness induced by mold toxins (mycotoxins) and other biotoxins.
Mold-induced illness (CIRS) has very similar symptoms to those of ME/CFS, but a different treatment (called the Shoemaker protocol). Patients with CIRS who are misdiagnosed with ME/CFS may thus get the wrong treatment. However, there is evidence that mold toxins may also play a role in ME/CFS. More info about CIRS diagnosis and treatment below.
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

Note that non-CDC-recommended labs such as ArminLabs and IGeneX are believed to have a high false positive rate (see this thread and this thread).

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.

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.

If you do have chronic Lyme, one new treatment is disulfiram. Though in a few patients, this seems to be causing neuropathy.1

Below are several comprehensive lists of diseases with similar symptoms to ME/CFS, for differential diagnosis purposes:

Standford University List of Diseases to Rule Out
ME Association differential diagnosis (from the ME Association's "Purple Book")
Open Medicine Foundation: Diagnosing and Treating ME/CFS (see page 3)
AAFP ME/CFS Differential Diagnosis (see table 1)

Overview of Possible ME/CFS Causes and Treatments
Once you have ruled out diseases with similar symptoms, and have settled on a diagnosis of ME/CFS, the next stage is to try to identify the underlying factors (infections, co-infections, toxic exposures, comorbid illnesses like orthostatic intolerance, allergies, intestinal dysbiosis, SIBO, etc) that may be causing or contributing to your chronic fatigue syndrome.

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 lab tests that people with chronic fatigue syndrome might choose to take. In this roadmap, the suggested tests are grouped into various rounds, with the most important tests placed in the earlier rounds. Here the focus is on tests which lead to a treatment, since this roadmap is treatment-oriented, and the goal is to introduce ME/CFS patients to therapies that may increase their level of health. The roadmap does not include tests which do not lead to a treatment, and whose results are just of academic interest.

After each round of testing, depending on the test results, indications for an appropriate treatment are given. The suggested treatment plans are those generally employed by leading ME/CFS doctors, and those which are backed up by published studies.

ME/CFS treatments which have a track record of helping (and can sometimes result in major improvements) include: Abilify, Valcyte, Valtrex, oxymatrine, vitamin B12 injections, tenofovir, GcMAF, IVIG, interferon, pyridostigmine and LDN. These treatments are detailed in later this document. See also: this list of ME/CFS recovery and improvement stories.

Furthermore, major improvements in health can be obtained by identifying and treating the various comorbid conditions that often accompany ME/CFS, which include: intestinal dysbiosis, SIBO, IBS, POTS, NMH, MCAS, allergies and low T3 syndrome. These conditions are explained in this roadmap document.

But there are no hard and fast rules for chronic fatigue syndrome treatment, and you may wish to follow different courses of action to those suggested here. Only you and your doctor can decide which treatments might be worth trying; nothing in this roadmap should be viewed as medical advice.

Bear in mind that the cause of ME/CFS remains unknown. Nevertheless, treating some of the underlying factors that doctors and researchers suspect play a role in ME/CFS often leads to improvements in symptoms.

Notes on Pathogen Testing
ME/CFS usually appears after an acute viral infection: typically a flu-like illness, a gastrointestinal upset, mononucleosis, or a sore throat. This sort of infectious onset occurs in up to 90% of ME/CFS patients.1 2 Furthermore, evidence of chronic active infection is found in ME/CFS, suggesting the acute infection which triggered the ME/CFS may have become persistent within the body.

Although there is controversy whether active infections cause ME/CFS, some patients improve from antivirals and immune boosters which target their chronic infections. ME/CFS specialists will often test patients for ME/CFS viruses, and if there is evidence of active infection, prescribe antiviral treatments or immune boosters.

ME/CFS-associated viruses and bacteria include: enteroviruses (specifically coxsackievirus B and echovirus), herpesviruses (specifically Epstein-Barr virus, HHV-6, cytomegalovirus and varicella zoster virus), parvovirus B19, SARS-CoV-2 coronavirus, and the intracellular bacterium Chlamydia pneumoniae.

In ME/CFS, evidence of chronic active infections with these pathogens is indicated by persistently high antibody levels, or by a positive PCR when infected tissues are tested. PCR blood tests are not often used, as not much virus can be found in the blood in ME/CFS.

Note that ME/CFS specialists interpret antibody tests in a different way to infectious disease doctors: the latter will usually ignore persistently high IgG antibodies if IgM is low; but ME/CFS specialists interpret persistently high IgG as evidence of a chronic active infection somewhere in the body. So to get properly tested, you are better off visiting an ME/CFS specialist (although these are few and far between).

In this roadmap, the intricacies of antibody testing in ME/CFS are detailed here.

If antibody testing suggests you have a chronic active infection with an ME/CFS-associated virus or bacterium, to an ME/CFS specialist, this means the 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, you may choose to bypass the test and go straight to treatment (if the treatment is safe and well tolerated). 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 for Viral Infections
The first round of ME/CFS potential causal factors to consider is shown in the table below. Various microbial and toxin causal factors are listed in the left hand column, and recommended tests for these causal factors (plus guidance on interpreting the test result) are given in the right hand column of the table.

The chronic viral infections frequently found in ME/CFS are: coxsackievirus B, echovirus, Epstein-Barr virus, HHV-6 and cytomegalovirus (and since the COVID pandemic, SARS-CoV-2 as well). ME/CFS doctors usually test for these. Most ME/CFS patients will have elevated antibody levels to one or more of these viruses.

But be aware that some ME/CFS doctors do not test for chronic coxsackievirus B or echovirus, or if they do test, they use blood tests which are not sufficiently sensitive enough to detect chronic infections. So ME/CFS can patients have these infections without knowing, if the wrong tests are used. The appropriate blood tests for chronic coxsackievirus B and echovirus are antibody tests using the neutralization method, detailed below.

If you would prefer a more concise overview of these viral infections, see the mini roadmap.

Possible Causal Factor Tests and Results Interpretation
Coxsackievirus B and Echovirus

These viruses have been strongly linked to ME/CFS in over 30 studies. There are 6 coxsackievirus B (CVB) serotypes and 32 echovirus (EV) 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. Rather the virus is mainly found as a chronic intracellular non-cytolytic infection in the tissues.1 2

PCR blood tests are not very sensitive for chronic enterovirus, because very little virus is found in the blood.

Whereas antibody tests, which do not detect the virus directly like PCR, but instead measure the immune antibody response to the virus, are more appropriate. Even if the virus is hidden in the tissues, an antibody blood test can provide evidence of this infection if the infection is extensive.

But not all antibody tests have the same sensitivity. Dr Chia found an antibody blood test using the neutralization method to be the most sensitive for chronic enterovirus. Neutralization is the gold standard in terms of test sensitivity.

Antibody tests by ELISA (EIA) and IFA are less sensitive, and antibody tests by CFT are insensitive in chronic infection. These methods are not reliable when testing for chronic enterovirus, Dr Chia found.

Dr John Chia observes that the CVB and echovirus serotypes most often found in ME/CFS are:1

• CVB3 and CVB4 first and foremost
• Then CVB2, EV6, EV7 and EV9
• And then much less EV11

► Go to CVB & EV treatments

Coxsackievirus B and echovirus antibody neutralization test. Dr John Chia says the only blood test sensitive enough to reliably detect chronic enterovirus infections in ME/CFS is an antibody test using the neutralization method (like micro-neutralization or plaque reduction neutralization).

Antibody tests employing the ELISA, IFA (immunofluorescence assay) or CFT (complement fixation test) methods he finds are not sensitive enough for detecting chronic enterovirus (these are only sensitive for acute enterovirus infections). PCR tests are also often not sensitive enough for detecting chronic enterovirus infections.

The following labs offer Dr Chia's recommended antibody test by the neutralization method:

ARUP Lab in Utah USA offer an antibody neutralization tests for coxsackievirus B and echovirus, costing around $200 each. These are the enterovirus lab tests Dr Chia uses himself.

You can order these tests directly from ARUP, or order via LabCorp or Quest. LabCorp order codes: 816869 for CVB, 823361 for EV. Quest have an ARUP Lab Miscellaneous Order code of 39651; this requires Quest to write on the order form the ARUP codes for the ARUP tests you want: 0060055 for CVB, 0060053 for EV.

Do check on your test results page that it says ARUP, because LabCorp and Quest often make errors, and perform these tests in-house using their own lab (which you do not want) rather than sending out to ARUP. See this thread which explains the issues.

You can order these ARUP tests more reliably (and without needing a doctor's order) through Any Lab Test Now.

Antibody titers of 1:160 to 1:320 and higher in the ARUP tests are good indicators of chronic active infection, Dr Chia found.1

Occasionally an ME/CFS patient may be infected with an enterovirus outside of the range tested for by ARUP. ARUP Lab only test for the 5 most common echoviruses, but there are over 30 echoviruses. This is when Dr Chia's stomach biopsy test is invaluable, as it can detect the presence of virtually all enteroviruses.

Cambridge Biomedical in Boston USA offer a antibody neutralization test for echovirus for $390, and is similar to the ARUP echovirus test. Cambridge Biomedical are now owned by BioAgilytix.

Hellenic Pasteur Institute in Greece provide a coxsackievirus B antibody neutralization test for €68. The lab director speaks English.

Institute of Clinical and Molecular Virology, Erlangen, Germany offer a coxsackievirus B1 to B6 antibody neutralization test. Patients abroad can contact their International Patient Office.
Institute of Medical Virology, University Hospital Frankfurt am Main in Germany provide individual antibody neutralization tests for coxsackievirus B1, B2, B3, B4 and B5, and echovirus 4, 6, 7, 9, 11, 25 and 30. These tests cost €34 for each serotype. Order form.

Torlak Institute of Virology in Serbia have a neutralization test for coxsackievirus B1 to B5 costing €200 (B6 is very rare, so a B6 test is not really needed).

Fleury Lab in Sao Paulo, Brazil offer a coxsackievirus B antibody neutralization test for $25. Fleury have clinics in major Brazilian cities where they take blood. It is not clear if they will accept blood serum samples from abroad.

Other than the above neutralization tests, another way used by Dr Chia to detect chronic enterovirus is via immunohistochemistry:

Stomach biopsy (immunohistochemistry). This test requires a sample of stomach tissue obtained by an endoscope. It is the most sensitive test for detecting a chronic enteroviral infection, although it will not indicate which particular CVB or EV serotypes you have.

You send your stomach tissue sample to Dr Chia's lab (also here) and he tests the tissue using immunohistochemistry. Cost is $250 (excluding endoscopy fees; you arrange the endoscopy yourself).

PCR blood tests are not very sensitive for chronic enteroviral infections, as enterovirus mostly disappears from the blood after the acute phase (the acute phase of an enterovirus infection starts just after initial exposure, and lasts for around 10 days). Dr Chia finds in whole blood samples, sensitive reverse transcription PCR blood tests will be positive about 30% of the time in patients with enterovirus ME/CFS (though severe patients test positive 70% of the time).1

Warning: do not get the ArminLabs coxsackievirus B test, as it is deceptive and a waste of money. This test only looks at CVB1, and does not test for coxsackievirus B2 to B6.

Some intricacies of viral testing in ME/CFS are explained here.

Further enterovirus testing info from Dr John Chia:
Enterovirus Foundation: Tests for Chronic Enteroviral Infections
Epstein-Barr Virus
EBV has been linked to ME/CFS.1 There is a high 95% prevalence of EBV in the general adult population, so most people will have this virus in their system, but usually in a latent (inactive) state. However, if you have active EBV, 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

Note: the active EBV infections thought to exist in ME/CFS are not the same as those found in the rare and often fatal illness chronic active Epstein-Barr virus (CAEBV). In CAEBV, high EBV viral loads are found in the blood by PCR, whereas in ME/CFS, blood PCR tests are usually negative for EBV (Dr Lerner proposed that in ME/CFS, EBV resides in the tissues, as an abortive infection).

► Go to EBV treatments
Epstein-Barr virus antibodies. Dr Martin Lerner says ME/CFS patients have an active EBV infection if there are high antibody levels in the VCA IgM and/or EA IgG diffuse tests.1 2

About 15% of EBV ME/CFS patients have positive VCA IgM, which indicates lytic replication, and is the signature of mononucleosis.1

Prof Jose Montoya has his own criteria based on high EBV VCA IgG and EBV EA IgG, but simultaneously required high HHV-6 IgG.1 2

What do we mean by high antibody levels? It is suggested that levels at least 16 times the lab reference for negative can be considered high. In the LabCorp EA IgG diffuse test, negative is <1:20, so the threshold for high antibody levels is calculated as 1:320 (since 16 x 20 = 320).

VCA IgM tests: LabCorp, Quest. UK/EU: Medichecks, ArminLabs.
EA IgG diffuse tests: LabCorp, Quest.

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

The EBV early antigen (EA) test can differentiate between active and latent EBV infection, because those early antigen antibodies disappear quickly after acute infection, so if you have them you know you are either active or have had a recent infection.1

Some intricacies of viral testing in ME/CFS are explained here.

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. 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

Dr Bhupesh Prusty has found that HHV-6 reactivation in cells causes mitochondrial dysfunction, and may cause this even in nearby cells which are not infected.1

► Go to HHV-6 treatments
HHV-6 IgM and IgG antibodies. Dr Martin Lerner says if you have both high IgM and high IgG antibody levels that indicates an active HHV-6 infection in ME/CFS.1 2

Prof Montoya has his own criteria based on high HHV-6 IgG, but also simultaneously requires high EBV VCA IgG & EBV EA IgG.1 2

What do we mean by high antibody levels? It is suggested that levels at least 16 times the lab reference for negative might be considered high. In the Quest IgG test, negative is <1:10, so the threshold for high antibody levels is calculated as 1:160 (since 16 x 1:10 = 1:160).

IgM and IgG tests together: Quest. UK/EU: ArminLabs.

The HHV-6 Foundation advise that ELISA IgG antibody tests are not appropriate for the chronic HHV-6 infections found in ME/CFS; they say IFA IgG antibody tests should be used instead. However for the HHV-6 IgM test, either ELISA or IFA are both fine.

Quest and ArminLabs offer IFA IgG antibody tests, linked to above.

LabCorp offer an HHV-6 IFA IgM & IgG antibody test via their test code ​821841 (LabCorp send out your sample to Eurofins Viracor).

Further info: HHV-6 Foundation: Viral Testing

The intricacies of viral testing in ME/CFS are explained here.
Cytomegalovirus (CMV) 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.

► Go to CMV treatments
Cytomegalovirus IgG antibodies. Dr Martin Lerner says high levels of IgG antibodies indicate an active infection in ME/CFS. Dr Lerner says testing CMV IgM levels has no relevance in ME/CFS.1

What do we mean by high antibody levels? It is suggested that levels at least 16 times the lab reference for negative might be considered high. In the LabCorp IgG test, negative is <0.60 so the threshold for high antibody levels is calculated as 10 (since 16 x 0.60 = 10).

IgG tests: LabCorp, Quest. UK/EU: Medichecks, ArminLabs.

Some intricacies of viral testing in ME/CFS are explained here.
SARS-CoV-2 Coronavirus
SARS-CoV-2 is a recent addition to the set of viruses which have been linked to triggering ME/CFS.

Little is known about the the ME/CFS form of long COVID, and there is no way of testing for it.

However, if one takes inspiration from other forms of ME/CFS linked to different viruses, it suggests that looking out for persistently elevated antibody levels may be a good indicator that coronavirus is involved.

SARS-CoV-2 presents a serious risk to existing ME/CFS patients. Two surveys (here and here) found that about one third of existing ME/CFS patients became permanently worse after COVID, and in many cases, greatly worse (some moved down 1 or 2 levels on the ME/CFS scale of: very severe, severe, moderate, mild, remission).

Catching SARS-CoV-2 more than once can also make long COVID patients much worse, according to this poll.

Though there are reports of existing ME/CFS becoming better after COVID (and even some rare stories of ME/CFS going into remission after catching SARS-CoV-2).

The medical name for long COVID is post-acute sequelae of COVID-19.

► Go to SARS-CoV-2 treatments
SARS-CoV-2 antibodies. SARS-CoV-2 antibody tests may help confirm that your ME/CFS symptoms are associated with the SARS-CoV-2 coronavirus.

No research has been published on antibody levels in the ME/CFS form of long COVID, but if an ME/CFS patient who suspects coronavirus involvement in their illness has persistent highly elevated antibody levels on a quantitative SARS-CoV-2 antibody test, by analogy to other ME/CFS viruses, this suggests SARS-CoV-2 may be behind your illness. This is because in ME/CFS patients with other viral infections, such chronically elevated antibody levels are also seen, and some ME/CFS doctors view elevated antibodies to a virus as evidence for that particular virus playing a role in the illness.

However, a confounding factor is coronavirus vaccination, which can also induce high antibody levels. So antibody tests which detect antibodies to SARS-CoV-2 spike protein will also be positive if you received a coronavirus vaccination.

But the existing types of COVID vaccination will not cause a positive result on antibody tests for SARS-CoV-2 nucleocapsid protein.1 So using nucleocapsid antibody tests, even if you have been vaccinated, you can still check to see whether you have previously caught coronavirus, and can test to see whether you have persistently high antibody levels.

Nucleocapsid antibody: LabCorp.

What do we mean by high antibody levels? It is suggested that levels at least 16 times the lab reference for negative might be considered high.

Confirmation that SARS-CoV-2 may be underpinning your ME/CFS symptoms could be useful for those who did not receive a coronavirus test during the acute phase of their viral infection, and so do not know for sure whether SARS-CoV-2 caused their illness.

Since the other viruses detailed in this roadmap can also trigger ME/CFS, unless you were tested during your acute infection to confirm SARS-CoV-2, you could have in fact caught a different ME/CFS-triggering virus, like enterovirus or EBV. But if you had a positive SARS-CoV-2 test (PCR or lateral flow) during the acute infection, this is good evidence that SARS-CoV-2 is behind your ME/CFS, and further viral testing may not be necessary.

Note that PCR blood tests may not be useful for long COVID ME/CFS once the acute infection is over, because in ME/CFS you typically find very little virus in the blood. In ME/CFS, the virus hides in the tissues rather than the blood, so PCR blood tests are often negative.1 

Some intricacies of viral testing in ME/CFS are explained here.
Parvovirus B19

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).

► Go to 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 high IgM antibodies.1

PCR tests: LabCorp, Quest. UK/EU: Medichecks.
IgM tests: LabCorp, Quest. UK/EU: Medichecks, ArminLabs.

Note: acute parvovirus B19 infection can create false positive IgM results when testing EBV, cytomegalovirus, HHV-6, herpes simplex and Borrelia burgdorferi sensu lato and others.1 2 This is due to parvovirus B19 IgM antibodies cross-reacting with the IgM antibodies of these other infections.
Varicella Zoster Virus
VZV causes chickenpox (varicella), and this virus can reactivate later in life to cause shingles (herpes zoster), a painful or itchy skin rash.

Dr John Chia finds about 2% of cases of ME/CFS are due to reactivated varicella zoster virus, and this form of ME/CFS can be treated remarkably easily with antiviral drugs such as acyclovir, which improve or cure the ME/CFS after around 3 weeks treatment.1

VZV ME/CFS thus differs markedly from the other forms of herpesvirus ME/CFS which are rarely curable, and require antiviral treatment for a year or two in order to obtain major improvements.

VZV is found in 63% to 100% of the population.1 Those who have an episode of shingles (VZV reactivation) have 1.3 times the risk of getting ME/CFS in the next 5 years.1

► Go to VZV treatments
The shingles rash caused by VZV is usually distinctive enough on its own to make an accurate diagnosis of VZV reactivation.1 Even just one or two shingles blisters can indicate varicella reactivation.

PCR testing of the shingles blister contents is the most reliable way to confirm VZV reactivation, if confirmation is required.

A shingles rash only appears on one side of the body, left or right, and will be confined to a strip or a small area. The most common locations for the shingles rash are shown here.

VZV normally lives in a latent state in the nerve ganglia (trigeminal and dorsal root ganglia), but when it reactivates it typically leads to shingles, and it has been hypothesized VZV reactivation in the nerve ganglia may sometimes cause ME/CFS.1

Note that enterovirus infections in their first two months have been shown to cause transient 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 shingles may just be due to this temporary immune weakening.

More info in this thread.
Chlamydia Pneumoniae
Chlamydia pneumoniae (Cpn) is an intracellular bacterium which Dr John Chia says an uncommon but treatable cause of ME/CFS.1

74% of the adult population have antibodies to Cpn, and about 10% of the adult population have a persistent active infection with this bacterium, according to a study conducted in Israel.1

► Go to Cpn treatments
Chlamydia pneumoniae IgG antibodies. Dr Chia notes that most ME/CFS patients with active Cpn infection will have high IgG antibody levels (but IgM is negative); however some with this infection will have low IgG levels.1 Thus low IgG level do not necessarily mean you do not have an active Cpn infection.

Cpn infection exists in two forms: in the initial phase, it is transmitted as an extracellular bacterium, and may cause flu-like attacks, separated by weeks of continual coughing, often resulting in chronic laryngitis. In the later stage Cpn changes to being an intracellular infection that persists for life, which may be asymptomatic, or may give rise to symptoms.1 One symptom of chronic Cpn may be a persistent cough.1

IgG tests: LabCorp, Quest. UK/EU: ArminLabs
Toxic Mold / Actinobacteria Exposure
Molds synthesize toxic substances called mycotoxins which can damage the immune system, 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.  Water damaged areas of buildings are also common places to find mold.

Mycotoxins from mold have been linked to ME/CFS. A study by Dr Joseph Brewer found several mycotoxins in ME/CFS patients were not found in healthy controls.1

Mold exposure can also trigger an illness that Dr Ritchie Shoemaker has called CIRS (chronic inflammatory response syndrome), a disease which can has similar symptoms to ME/CFS, and can be misdiagnosed as ME/CFS.

So mold exposure might be a causal factor in the development of your ME/CFS, or it may alternatively have triggered the ME/CFS-like illness of CIRS.

CIRS is not the same as mold allergy. Mold allergy is typically a mild condition in which mold causes hay fever-like allergic symptoms such as a runny nose and itchy eyes. Whereas CIRS is a serious chronic illness induced by biotoxins.

Mold is a biotoxin. Other biotoxins such as toxins from cyanobacteria (a toxic blue-green algae found on lakes) may also be involved in triggering ME/CFS and CIRS.

In the 1984 Lake Tahoe outbreak of ME/CFS, one dual-factor theory points to a toxic cyanobacteria present on the lake at the time of the outbreak.

Mycotoxins are not the only toxic substance produced by mold. Mold also creates mold VOCs (responsible for the musty smell of mold), which potentially may cause ill health effects (though research on this is still in its infancy).1

More recently, Actinobacteria have been implicated in CIRS. Actinobacteria grow in the same damp places as mold, and along with mold, may lead to CIRS.1

Dr Shoemaker's Actino Central explores Actinobacteria in CIRS.

► Go to toxic mold 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. 92% of people with biotoxin-induced CIRS illness have a positive VCS test.1

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. Dr 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. Typical CIRS symptoms are listed here. Shoemaker found 24% of the population have a haplotype that makes them susceptible to developing CIRS after exposure to biotoxins, as some haplotypes cannot properly detoxify biotoxins from their body. Dr Shoemaker says a HLA DR test can determine if you have a susceptible haplotype (this diagram shows the susceptible haplotypes). Having such genetic susceptibility is one of the criteria required for a CIRS diagnosis, with the other criteria detailed on page 4 of this document (but the utility of HLA DR testing to aid CIRS diagnosis has been questioned).

Nasal infections with MARCoNS are common in CIRS, and these can be tested at this lab.

Note: no independent researchers have confirmed CIRS exists as a clinical entity; thus Dr Shoemaker's CIRS illness still awaits confirmation by the wider scientific community.

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

1ST ROUND: Treatments for Viral Infections
In the light of the results of the first round of tests, the following treatments can be employed. These 1st round treatments are sometimes capable of moving a patient up by one or two levels 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. These treatments can occasionally even lead to full remission, but that is rare.

Do not forget that nothing in this roadmap should be construed as medical advice. Only you and your doctor can decide which treatments are appropriate for you.

Coxsackievirus B and echovirus treatments. If your tests indicate you have an active infection with coxsackievirus B3 or B4, Dr John Chia finds about 30% of ME/CFS patients make major improvements with an immunomodulator called oxymatrine.1 2 However oxymatrine does not work for echovirus.1

Dr Chia suggests patients with autoimmune tendencies should not take oxymatrine, as there is a risk it may trigger rheumatoid arthritis — see this thread post. Oxymatrine is best avoided in young children and during pregnancy.1

Oxymatrine supplements can be bought online without prescription. Dr Chia has formulated his own brand of oxymatrine called Equilibrant, but you can also buy White Tiger oxymatrine, which Dr Chia finds works with similar efficacy. Oxymatrine treatment begins by taking half an Equilibrant capsule for the first week or two, then slowly increasing up to 2 or 3 capsules twice daily (a total of 4 to 6 capsules daily). See this video interview with Dr Chia at 4:24. No escalation of dose should be made if there is a significant increase in symptoms (wait until the symptoms settle).1

The exact dose of oxymatrine in Equilibrant is not known, as this is a proprietary formulation. However, on the Alternative Medicine Solutions website it suggest an oxymatrine dose of 400 to 600 mg daily.1 Oxymatrine may best be taken in divided doses (eg morning and night).

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). Women however usually have to continue taking oxymatrine, otherwise they relapse.1 Dr Chia says inosine can be taken with oxymatrine in order to augment the effects.1 When taken with inosine, the oxymatrine dose can be reduced to 3 or 4 tablets a day. Dr Chia sometimes adds rifampin (also called rifampicin) 300 mg twice daily for 7 days to boost the immunomodulatory action of oxymatrine.1 2

More info on oxymatrine:
Dr Chia: Oxymatrine Treatment PresentationDr Chia: OxymatrineOxymatrine, Autoimmunity, ME/CFS and FMQuixotic: EquilibrantInvest in ME 2010 Conference video (at 31:30) • Invest in ME 2010 transcriptOxymatrine EffectsImmunomodulators 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 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 major).1 2 Dr William Weir has in the past treated a few ME/CFS patients with tenofovir with some success, but noted some patients got worse on this drug. Tenofovir may be effective against the low-level infections found in ME/CFS.1 Tenofovir is also effective against human endogenous retrovirus (HERV) infections,1 which may be active in ME/CFS.1 HERVs are naturally present in all humans, but are normally inactive; however enteroviruses and EBV can cause HERVs to activate.1 Note that tenofovir and Valcyte do not mix.1

Some ME/CFS patients find tenofovir hard to tolerate, and in these cases low doses can be used initially and the dose slowly built up. The full dose of tenofovir disoproxil fumarate is 300 mg daily, but patients may want to start on an eighth or a sixteenth of a 300 mg tablet.

Tenofovir can cause mitochondrial toxicity; supplements which might help counter this detailed in this thread post. Tenofovir can cause serious life-threatening side effects, including lactic acidosis, kidney problems and severe liver problems, see here. When taking tenofovir, regular kidney function blood tests are required.

Tenofovir alafenamide (TAF) may be safer than tenofovir disoproxil fumarate (TDF), as TAF appears to have less kidney and bone side effects. A dose of 25 mg of TAF is equivalent to 300 mg of TDF.1

Dr Chia has also tried interferon therapy for enterovirus-associated ME/CFS with some dramatic results (cost around $18,000 for a course lasting a few months). Around half the severe bedbound patients treated with interferon alpha plus delta returned to work after the therapy, but unfortunately tended to relapse after around 4 to 14 months later (typically after a heavy bout of exercise). In another experiment, two ME/CFS patients given interferon alpha plus gamma went into remission, with these improvements lasting for about 14 months before relapsed occurred.1 2 3 And a few patients had remission of symptoms for as long as 2 to 3 years.1

Interferon works for ME/CFS linked to CVB3 or CVB5, but Dr Chia found it does not work for CVB4.1 2 Dr Chia rarely uses interferon now, because he says patients cannot tolerate it (see this video at 3:51).

Dr Chia does employ interferon beta to treat severe bedbound hospitalized ME/CFS patients, as he finds after two weeks treatment, those patients "are up, walking around the hospital five times". But Dr Chia says that the positive effects of interferon beta only last for 3 to 6 months.1

More info on interferon therapy: Chia's Interferon Therapy, Interferon - MEpedia.

Some interesting "interviews" with Dr Chia, focusing on his treatments, in these five posts: 1 2 3 4 5 Many of Dr Chia's conference presentation and interview videos are listed here.

Two new antiviral drugs (code named Rega Compound A and Rega Compound 17) that are potent antivirals for coxsackievirus B are expected to become available in a few years (see this thread). These drugs were originally developed by the Rega Institute. Compound A targets CVB4, and completely eliminates CVB4 from the tissues and organs of mice. Compound 17 works against CVB3, CVB4, CVB5 and CVB6. It is possible these new drugs will substantially improve ME/CFS associated with coxsackievirus B.
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. A patient survey found that a massive 50% of ME/CFS patients taking Valcyte made a major improvement.

One study found spironolactone 25 mg daily resulted in 31% of EBV ME/CFS patients achieving full remission, and 69% observing improvements in their ME/CFS symptoms.1 More info in this thread.

Tenofovir has modest in vivo antiviral effects against EBV lytic DNA replication.1

Ritonavir has anti-EBV effects,1 and Dr Jonas Axelsson uses it to treat ME/CFS (recovery story here).
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 Some Valcyte success stories detailed in this thread.

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.

The antimalarial drug artesunate may have some 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 high-dose valacyclovir (Valtrex) or famciclovir (Famvir) are effective for CMV, with 2000 mg of Valtrex or Famvir equivalent to 450 mg of Valcyte.1 2 3 4 5 By contrast the Merck Manual says acyclovir/Valtrex has minimal activity against CMV, and Dr Lerner found ME/CFS patients with active EBV improved on Valtrex, those with both active EBV and CMV did not improve.1 So it is not clear if these will work for CMV ME/CFS. Of the two drugs, Famvir may be better, as its intracellular half-life is longer.1
SARS-CoV-2 coronavirus treatments. There are several  reports of long COVID patients getting rapid and substantial improvements from the supplement lactoferrin at doses of around 1500 mg daily. Though as with many anecdotes about LC treatments, it is not always clear whether these patients have the ME/CFS form of LC, or some other form of LC (such as POTS, or heart and lung damage).

A study observed that the H1 antihistamine loratadine 10 mg twice daily in combination with the H2 antihistamine famotidine 40 mg once daily led to improvements in 72% of long COVID patients.1 In a case report, famotidine improved LC neuropsychiatric symptoms.1

Several long COVID patients report major improvements within days from diphenhydramine (Benadryl) 25 mg before bed. Others get major improvements from hydroxyzine 25 mg before bed. See here

Some LC patients have reported improvements after a few weeks on the antiviral sofosbuvir.1
Some LC patients have experimented with the antiviral Paxlovid (nirmatrelvir + ritonavir), but success stories are not common with this drug. A study of 13 patients found Paxlovid can improve LC symptoms in some people, but not others; though not all the benefits are maintained after the drug is stopped.1

Studies show LC patients (not necessarily ME/CFS LC patients) improve after COVID vaccination.1 One study on LC patients however found that 62% improve and 19% get worse after a COVID vaccination.1

The monoclonal antibody drug REGEN-COV (containing casirivimab and imdevimab) has completely cured three long COVID patients.1 2
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).
Varicella zoster virus treatment. If you have a reactivated infection with varicella zoster virus (which will normally present as as a shingles rash), then treatment with one of the antiviral drugs acyclovir, valacyclovir (Valtrex) or famciclovir (Famvir) can quickly cure this form of ME/CFS.1 Dr John Chia has found that patients with reactivated VZV can dramatically improve within weeks on such antivirals.

One severe bedbound ME/CFS patient who had just two shingles blisters returned to work after 3 weeks on acyclovir — see timecode 6:58 in this video interview of Dr Chia. The normal Valtrex dose for shingles is 1,000 mg three times daily.1 More info on VZV ME/CFS in this thread.

Brivudine (Zostex) 125 mg once daily for 7 days is a very potent antiviral for varicella zoster virus (this drug should not be used for longer than 7 days).1 The H2 antihistamine cimetidine 200 mg three times daily plus 400 mg just before bed can be an effective off-label treatment for varicella zoster virus.1 2
Chlamydia pneumoniae treatments. If your tests indicate you have an active infection Chlamydia pneumoniae, then antibiotic treatment with azithromycin 250 mg daily for one or two months is effective. However relapse is common, requiring repeated treatment.1

A combination of azithromycin with rifampin or doxycycline is more likely to fully eradicate Cpn.1
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 a 12 step protocol to treat CIRS. The first step involves identifying and removing the source of toxic mold, the next step involves using cholestyramine to detoxify mycotoxins from the body, 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 list of doctors trained in the Shoemaker protocol give here and also in the Map of ME/CFS & CIRS Doctors.

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, and thus not get better. 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 antifungal 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 antifungal nasal spray used by the Brewer mold protocol, can be purchased at Woodland Hills Pharmacy.

Note that some cases of ME/CFS may involve a combination of the above infections, as well as other factors. In which case, it may be possible to combine the above treatments in order to tackle the infections.

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

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 Drug
Viruses Targeted
Valtrex (valacyclovir) EBV


Famvir (famciclovir) EBV


Valcyte (valganciclovir) EBV HHV6 CMV VZV HSV1 HSV2

Vistide (cidofovir) EBV HHV6 CMV VZV HSV1 HSV2

Falcigo (artesunate) EBV HHV6 CMV

Foscavir (foscarnet)

Prevymis (letermovir)


Zostex (brivudine)






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

Some studies suggest high-dose Valtrex or Famvir might possibly effective for CMV (see CMV treatments).

Valacyclovir is the prodrug of acyclovir, meaning valacyclovir converts into acyclovir in the body. Likewise, famciclovir is the prodrug of penciclovir, valganciclovir is the prodrug of ganciclovir. Valganciclovir, cidofovir and foscarnet can sometimes cause serious side effects, so their use must be monitored by a doctor.

General Therapies for ME/CFS
As well as the above therapies targeted at specific pathogens, there are many general therapies that can be helpful in chronic fatigue syndrome. These include:

Antiviral immunomodulators. Immunomodulators 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. To fight the viral and intracellular bacterial pathogens linked to ME/CFS requires the Th1 mode.

ME/CFS patients may be undesirably shifted towards the Th2 mode,1 which can then result in suppression of the antiviral Th1 mode. Immunomodulators such as oxymatrine and inosine can shift the immune response away from Th2 and back to Th1, helping to clear viral infections.

Oxymatrine is a Th2-to-Th1 immunomodulator used to treat coxsackievirus B-associated ME/CFS, and is detailed in the coxsackievirus B and echovirus treatments section.

Inosine is a Th2-to-Th1 immunomodulator (there is a drug version of inosine called Imunovir, which may be more effective, but is 10 times the price).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. 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 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 boosts virus-induced interferon beta.1

GcMAF is a protein which stimulates macrophages to fight pathogens in the body. ME/CFS patients have reported improvements from GcMAF, and case studies suggest it may be useful in ME/CFS.1 It is often found that one brand of GcMAF works well for a patient, whereas another brand has no effect. Unfortunately regulators have been closing down GcMAF manufacturers, so many brands are no longer available. Some sources for GcMAF in this post.

More info about the immunomodulators used in chronic fatigue syndrome given in this thread post.
Rituximab (Rituxan) is an anti-autoimmunity drug which depletes B-cells in the blood, thereby reducing the autoantibodies that are made by B-cells. Two phase II clinical trials of rituximab for ME/CFS showed 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 serious doubt on rituximab as an ME/CFS treatment (except perhaps in certain patients where autoimmunity is present).1 2

On the Phoenix Rising ME/CFS forum, out of over 30 ME/CFS patients with no comorbid autoimmune diseases who tried rituximab, only 1 benefited (moderately, but not cured). There have been at least two cases of ME/CFS patients being made permanently much worse after rituximab treatment,1 and one case of an ME/CFS patient (herself a doctor) who sadly died as a result of rituximab treatment.1

Rituximab treatment for ME/CFS patients is available at the Open Medicine Institute, California ($50,000) and Kolibri Medical, Stavanger, Norway ($15,000). More info about Kolibri here.

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 An ME/CFS patient survey found 57% experienced benefits from LDN. LDN seems to help fibromyalgia patients the most.1 A case study showed benefit.1 LDN is cheap, costing $6 per month.

LDN has multiple 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 this thread.

More info on LDN: LDN for Chronic Fatigue Syndrome, LDN Overview, Low-dose naltrexone - MEpedia.
Vitamin B12 injections. Many ME/CFS patients find that vitamin B12 injections, which provide high doses of B12, substantially reduce their brain fog and fatigue symptoms. The recommended forms of vitamin B12 are methylcobalamin, adenosylcobalamin or hydroxocobalamin (the first two are the active forms).

Injectable B12 doses are typically 1000 mcg three times a week. Improvements in symptoms usually appear after a few weeks of taking B12. One study found that ME/CFS patients taking methylcobalamin responded better than those taking hydroxocobalamin.1 A list of online B12 injection suppliers in this thread post.

High dose B12 can cause transient low blood potassium (hypokalemia) a few hours after injecting the B12, which may manifest as tiredness. This may be prevented by taking 300 mg of oral potassium.

An alternative to injection is Dr Greg Russell-Jones's B12 transdermal oil. This uses a new technology called micro-emulsion penetration enhancement to pull B12 through the skin. With this technology, estimated 80% is absorbed, allowing B12 oil to provide systemic doses comparable to injections. Greg recommends the methylcobalamin + adenosylcobalamin B12 oil for ME/CFS. More info in this thread.

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 the following daily supplements: vitamin B12 hydroxocobalamin 2000 mcg sublingual, methylfolate 200 mcg, folinic acid 200 mcg, lecithin 1200 mg, 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). Some patients find the methylation protocol does not work until they switch to the methylcobalamin form of vitamin B12 rather than using the hydroxocobalamin form.

Rich's informal study of 30 ME/CFS patients found that 27% of them achieved major improvements from methylation after 3 months.1 Patients found it took an average of 5 to 6 weeks before the protocol started to work. However, a patient survey found methylation was not hugely effective, with only 3% of patients experiencing a major improvement, though 28% reported a more minor improvement.

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

More info about methylation: Glutathione and the Methylation Cycle, Methylation cycle hypothesis - MEpedia.
High-dose thiamine. A survey found 66% of ME/CFS patients observed large improvements in their fatigue, post-exertional malaise and brain fog when taking high doses of thiamine (vitamin B1). The dosage used by these patients was from 200 mg daily, up to 1500 mg daily. A study also noted similar benefits for ME/CFS from high dose thiamine.
Low-dose Abilify. One preliminary study found that low doses of the drug Abilify (aripiprazole) from 0.2 to 2.0 mg daily can benefit ME/CFS.1 Several ME/CFS patients have reported that low-dose Abilify rapidly leads to major improvements in their symptoms, see here: 1 2 3 4 5 6 7 However, there are also reports of the benefits of Abilify fading after a few months.1

Abilify is a third-generation antipsychotic that can occasionally cause serious side effects. Although the fact that low doses of Abilify are used to treat ME/CFS may decrease the risk of these side effects.

Abilify for ME/CFS Facebook group here. A patient poll on the benefits they observed from Abilify here.
Nimodipine. The calcium channel blocker nimodipine which increases blood flow to the brain is prescribed by several ME/CFS specialists. Dr David Mason Brown says nimodipine helps 20% of ME/CFS patients very quickly, and another 20% over six months.

The Mason Brown protocol begins with a quarter of tablet (7.5 mg) of nimodipine per day with food. Then slowly increase the dosage by a quarter of a 30 mg tablet each week, up to a maximum dose of four tablets per day (taken in divided doses). It is important to drink 8 glasses of water each day. When headache, flushing, nausea or rapid heartbeat is brought on by a new dose, continue another week at the old dose before trying the increase again. If the symptoms re-occur, then the old dose is your maximum effective dose.1 Some patients find nimodipine lowers blood pressure, so have to cease taking it.1 Nimodipine has many drug interactions.

An alternative to nimodipine is the antihistamine and calcium channel blocker drug cinnarizine, which has anecdotally shown benefit in ME/CFS (see this report). Cinnarizine is available over the counter in the UK.

Prof Martin Pall suggests calcium channel blockers may be helpful for those with electrosensitivity (electromagnetic hypersensitivity).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 injections improve energy levels and emotional state, and results in less pain in ME/CFS (transdermal magnesium is an alternative to injections).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 High cocoa polyphenol rich chocolate may improve ME/CFS symptoms.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 (Panax ginseng plus B vitamins) improve fatigue in ME/CFS.1 Multivitamin and multimineral 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.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
Reducing fatigue and increasing energy. Fatigue and low energy are cardinal symptoms of ME/CFS. Some studies indicate there is a blockage in mitochondrial energy metabolism in ME/CFS.1

Methylphenidate (Ritalin) 10 mg twice daily substantially reduces fatigue and improves concentration, and works for around 1 in 3 patients.1 2 Ritalin may stimulate mitochondrial functioning.1 Agomelatine 50 mg daily improves fatigue in ME/CFS.1 Dr David Bell found amantadine 25 mg to 50 mg twice daily helps reduce fatigue ME/CFS, but says higher doses can exacerbate symptoms.1 Very low-dose amisulpride 25 mg twice daily reduces fatigue and somatic symptoms, and is well tolerated.1 Moclobemide 450 mg daily increases the sense of vigor and energy in ME/CFS.1

Dichloroacetate (DCA), which stimulates mitochondrial energy metabolism, improves fatigue, brain fog and pain in just over 1 in 3 ME/CFS patients (those with comorbid autoimmune conditions are less likely to respond).1 2 See these tips for avoiding the possible neuropathy side effects of DCA.

Low-dose hydrocortisone (5 to 20 mg daily) reduces fatigue and improves wellness, though it can suppress adrenal glucocorticoid responsiveness in some patients.1 2 Note that even low-dose corticosteroids such as hydrocortisone can increase the risk of psychiatric disorders.1
Treating brain fog. Brain fog (also called cognitive dysfunction and clouding of consciousness) involves short-term memory and working memory problems, difficulties in concentration, difficulties in multitasking, confusion, disorientation, and slowness or temporary inability to retrieve the right word from memory.

High-dose vitamin B12 injections often reduce brain fog quite noticeably (see B12 section). The drug piracetam 800 mg to 2,400 mg daily (can also be bought as a supplement) can treat brain fog symptoms and also improves blood microcirculation and mitochondrial functioning. Some report a bit of emotional flattening on piracetam, but this can be minimized by using the lowest dose.1 Several ME/CFS doctors find the stimulant drug modafinil helpful for some ME/CFS patients, to improve cognition.1 More info about modafinil this thread post.
Treating post-exertional malaise (PEM). When ME/CFS patients exert themselves physically or mentally, this often leads to PEM, which is a period of substantial worsening of ME/CFS symptoms (including worsened fatigue, brain fog and pain) as well as a feeling of malaise and sometimes flu-like symptoms. PEM typically begins the next day after exertion (although it can appear faster, or sometimes be delayed for a few days). Once PEM begins, it can last for several days, sometimes several weeks, before the patient recovers to their normal illness baseline.

Anecdotally, the following drugs and supplements are reported to help prevent PEM occurring after physical or cognitive exertion ("PEM shielders"), or speed up the recovery from PEM once it does occur ("PEM relievers").

PEM shielders: Some ME/CFS patients find pyridostigmine at around 45 mg x 3 times daily greatly reduces or stops PEM, and generally improves their ME/CFS. A one-off dose of prednisolone 20 mg taken 30 minutes before exertion may completely prevent PEM (but these doses of prednisolone should not be used daily, only occasionally, as the immunosuppressive effects of daily prednisolone may allow underlying viral infections to proliferate). The kitchen spice cumin (Cuminum cyminum) at one level teaspoon taken every few days is often a good PEM shielder. Cumin contains cuminaldehyde, which has known mitochondrial effects.

PEM relievers: D-ribose 5 grams three times daily works for some to speed up recovery from PEM.

More info on these PEM preventers in this comprehensive "PEM busters" thread.
Treatments sensory overload, the "wired" mental state, and sleep. ME/CFS often involves a "wired but tired" hyperaroused mental state, which may be due to elevated brain glutamate levels. And many ME/CFS patients also experience sensory overload, where the brain has difficulty in filtering out non-relevant sensory stimuli (a sensory gating issue).

For some patients, N-acetyl cysteine 600 mg taken three times daily reduces the wired symptoms of ME/CFS, probably by its ability to reduce brain glutamate.1

The benzodiazepine drug clonazepam (Klonopin) reduces 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 on stopping.1

The anticonvulsant gabapentin (Neurontin) helps reduce pain, reduces oversensitivity to stimuli, and enhances deep sleep; but on discontinuation this drug can cause withdrawal symptoms which can last for months.1 More sleep drugs for ME/CFS detailed here.

Dr Lapp finds melatonin useful for circadian rhythm-shifted patients who cannot get to sleep until very late at night.1

Dr Rodger Murphree finds 5-HTP 50 mg or more 30 minutes before bed helps sleep (see here).
Treating anxiety and depression. Around a third of ME/CFS patients also suffer depression, and another third suffer from an anxiety disorder such as generalized anxiety disorder (GAD) or panic disorder (PD).1 2

Standard treatment for anxiety involves SSRI drugs such as escitalopram or benzodiazepines such as clonazepam. But SSRIs often cause permanent sexual dysfunction and emotional flattening,1 and benzodiazepines often lead to nasty protracted withdrawal symptoms.1

As an alternative to these anti-anxiety drugs, a treatment for GAD that many ME/CFS patients report effective is the three supplement anti-anxiety protocol, and in particular the supplement N-acetyl-glucosamine (NAG) which has potent anti-anxiety effects.

One study found probiotics reduce anxiety symptoms in ME/CFS.1

Treatments for depression include SSRIs like fluoxetine (Prozac), TCAs like amitriptyline, and MAOIs like moclobemide (moclobemide has the lowest incidence of sexual side effects out of these antidepressants).1

Supplements which have potent antidepressant effects comparable to these drugs include Spanish saffron 100 mg twice daily (but be careful to avoid fake saffron)1 and curcumin which is an MAOI.1
Treatments for overstimulation. ME/CFS can sometimes involve an overstimulated mental state, which may be due to too much norepinephrine in the brain. Such overstimulation feels very similar to anxiety, though with overstimulation, there is none of the worry or mental tension that you get with anxiety, just a feeling like drinking too much coffee.

In the overstimulated state, you can be driven to be very productive, but it is not a pleasant state, as you are not relaxed. Overstimulation can occur spontaneously, or can be caused by overmethylation from taking too much methylfolate. A standard treatment for overstimulation is niacinamide 1000 mg.

Links to various other lists of ME/CFS treatments and therapies:
Erica Verrillo and Lauren Gellman's book "CFS Treatment Guide" (1st edition available for free online)
ME/CFS treatment recommendations, US ME/CFS Clinician Coalition
Chronic Fatigue Syndrome Treatment – Wikipedia
Treatments for ME/CFS (CFSsufferer's blog)
Dr Jacob Teitelbaum's 30 Top Tips for Treating CFS Part 1, Part 2 and Part 3
ME/CFS Medications Database
Dr Jay Goldstein's ME/CFS drug treatments
Chronic Fatigue Syndrome Treatments at Phoenix Rising

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

2ND ROUND: Tests for Comorbid Diseases
This second round focuses on some of the comorbid illnesses that are frequently found in ME/CFS patients.

Comorbid conditions that are statistically more prevalent in chronic fatigue syndrome or fibromyalgia patients 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, low T3 syndrome, Hashimoto's thyroiditis, prolapsed mitral valve, metabolic syndrome, Sjögren's syndrome (sicca syndrome), postural orthostatic tachycardia syndrome (POTS), neurally mediated hypotension, hypermobile Ehlers-Danlos syndrome, psoriasis and people who experienced abrupt early-onset OCD or pediatric acute-onset neuropsychiatric syndrome (PANS) as a child.1 2 3 4 5 6 7 8 9  

These comorbid conditions may exacerbate ME/CFS symptoms, and/or bring new symptoms of their own. Some of these comorbidities might play a causal role in the development of ME/CFS.

Possible Causal Factor Tests and Results Interpretation
Intestinal Dysbiosis
Intestinal dysbiosis is where the populations of harmful bacteria or fungi in the large intestine (colon) outweigh the populations of beneficial bacteria. People with ME/CFS often have intestinal dysbiosis, and their colon may harbor some pathogenic microbial species.1 2 These conditions may be contributing to your ME/CFS symptoms.

► Go to 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 precisely control which substances can pass through the intestinal wall.

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

One study found 39% of those with diarrhea predominant IBS (IBS-D) were found to have leaky gut.1

► Go to leaky gut treatments
Lactulose/mannitol test. This 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.1

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

Irritable Bowel Syndrome (IBS)
IBS symptoms may include: abdominal pain and bloating; bouts of diarrhea 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

► Go to 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. Normally the small intestine has very low levels of bacteria (it is almost sterile, in contrast to the large intestine, which has high numbers of bacteria).

The symptoms of SIBO are similar to those of IBS, and can include: abdominal pain, nausea, bloating, indigestion, an uncomfortable feeling of fullness after eating, loss of appetite, passing a lot of gas (flatulence), diarrhea or constipation, fatigue and weakness.1

One study found 77% of ME/CFS patients have SIBO, and found treatment of the SIBO led to improvements in ME/CFS symptoms.1

SIBO is common in IBS patients, and eradication of SIBO has been shown to improve the symptoms of IBS.1 2

► Go to SIBO treatments
Hydrogen/methane breath test. SIBO can be detected using a breath test, which involves drinking some lactulose or glucose 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). Genova Diagnostics provide a home SIBO test which involves drinking some lactulose and breathing into tubes. Other SIBO breath tests listed here.

The lactulose breath test detects SIBO located at the distal end of the small intestine (thought to be more common). The glucose breath test detects SIBO in the proximal part of the small intestine (the part next to the stomach).1

In some cases of SIBO, no hydrogen or methane gas is produced in the breath test, but hydrogen sulfide gas is produced. Until recently, no commercial test could detect hydrogen sulfide, but the Trio Smart SIBO breath test detects all three gases.

Methane SIBO tends to cause constipation (as methane gas slows intestinal transit time), whereas hydrogen SIBO (and hydrogen sulfide SIBO) tends to cause diarrhea.1

The methane in SIBO is not produced by bacteria, but by organisms such as Methanobrevibacter smithii which are classified as archaea. For this reason, methane SIBO now has its own name of intestinal methanogen overgrowth (IMO), since these methane-producing organisms are not bacteria.

Unfortunately the sensitivity and specificity of the SIBO breath tests are low: at 55% and 83% respectively for the glucose breath test.1 This leads to many false negatives, and some false positive results, as only 55% of people who actually have SIBO will receive a correct positive result on this glucose breath test (the other 45% will receive an incorrect negative result); and only 83% of people who do not actually have SIBO will get a correct negative result (17% will get an incorrect positive result). The sensitivity/specificity for the lactulose SIBO test are slightly worse.

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:
Small intestinal bacterial overgrowth — MEpedia
Testing for SIBO (informative website by Dr Allison Siebecker).
Labs that offer hydrogen/methane breath tests.
Bacterial Dysbiosis in the Kidneys

Dr Igor Markov in the Ukraine says ME/CFS is due to a chronic bacterial dysbiosis in the kidneys (not the same as a kidney infection).

Dr Markov says this kidney dysbiosis constantly leaks bacterial toxins into the bloodstream, and these toxins cause a condition he names the chronic bacterial intoxication syndrome (CBIS). This CBIS in turn he says causes ME/CFS. Dr Markov treats the kidney dysbiosis with autovaccines, and claims this treatment permanently cures 93% of ME/CFS patients.

► Go to Kidney dysbiosis treatments
Dr Markov's High Sensitivity Urine Test. To test for the presence of bacterial dysbiosis in the kidneys, which is the first step to obtain a CBIS diagnosis, Dr Markov uses a special high-sensitivity urine culture test. A regular urine bacterial culture test used for detecting kidney infections will not suffice, because in this kidney dysbiosis, the levels of bacteria in the urine are lower than you find in a regular kidney infection. So a high-sensitivity test is needed.

ME/CFS patients can perform this high-sensitivity urine test at home, by purchasing some urine dipslide products (not the same a urine dipstick) which are used to capture and grow the bacteria found in the urine.

Instructions for performing the high-sensitivity urine test at home can be found in this document, under the section "Performing a Home Urine Culture Test to Capture Bacteria".

An introduction to Dr Markov's CBIS theory of ME/CFS is found in the first post of this thread (the post also contains links to further information). See also this article on the CBIS theory. 
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

► Go to 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.1

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.
Low T3 Syndrome

Around 1 in 6 ME/CFS patients suffer from low T3 syndrome, in which levels of the thyroid hormone triiodothyronine (T3) are low, and levels of reverse T3 are high, even though levels of thyroid stimulating hormone (TSH) are normal.1 This represents a subclinical hypothyroidism, which may exacerbate ME/CFS symptoms, but may not be detected by regular thyroid hormone testing, which usually only checks TSH and thyroxine (T4).

► Go to low T3 syndrome treatments
Comprehensive thyroid hormone test. A comprehensive thyroid test which includes TSH, free T4, free T3 and ideally reverse T3 can detect low T3 syndrome.

In the UK, you may be able to get a comprehensive thyroid test through your GP; if not you can order a thyroid test privately.
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.

► Go to POTS treatments d
POTS is diagnosed by the tilt table test or the active standing test. These two approaches are comparable in accuracy.1

The active standing test can easily be performed at home by the patient. This test involves measuring the increase in your heart rate when you stand up from a relaxed lying down position.

To perform this active standing test, you lie down horizontally for 5 minutes or so and relax. When you feel completely relaxed, measure your heart rate in terms of beats per minute (bpm) while still lying down.

Then stand up, and monitor your heart rate over the next 10 minutes while standing, but without walking around or talking.

If your heart rate at any time in the next 10 minutes goes up by 30 bpm or more in a sustained manner, compared to your lying down heart rate, then you are diagnosed with POTS.

For those aged 12 to 19, the increase of heart rate on standing needs to be 40 bpm or more for a POTS diagnosis.1 2 3 4        

However the above POTS diagnosis is only valid if you do not have orthostatic hypotension, which is where your blood pressure substantially decreases on standing.

So in order to to perform the POTS diagnosis correctly, you really need to check for any change in blood pressure on standing with a blood pressure meter, and see if you have orthostatic hypotension. The next section describes how test for orthostatic hypotension.

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 for the active standing test, the threshold for diagnosis may be set at 27 bpm rather than 30.1

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

Further info on POTS: – Articles – Diagnosis – Treatments
Neurally Mediated Hypotension and Orthostatic Hypotension

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 lightheadedness, 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

► Go to 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.

OH is also called:
• Postural hypotension

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 loss of consciousness due to a drop in blood pressure). More info on the diagnostic technique used for NMH is given here.

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

More info:
Orthostatic Hypotension
Neurally Mediated Hypotension and its Treatment

2ND ROUND: Treatments for Comorbid Diseases
In the light of the results of the second round of tests, the following treatments may be useful:

Intestinal dysbiosis treatments. If your digestive stool analysis indicates bacterial overgrowth and/or the presence of some pathogenic gut bacteria, a course of antibiotics and/or probiotics may help. Dr Kenny De Meirleir uses the unique Escherichia coli probiotic Mutaflor to treat gut dysbiosis (Symbioflor is a Mutaflor alternative); he may also prescribe a cycled treatment taking the the antibiotic rifaximin for 15 days, then taking Mutaflor for the next 15 days, and repeating this each month.1 Though note that some ME/CFS patients 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, possibly making it harder for your body to fight 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 ME/CFS can be obtained by normalizing a leaky gut.1

A comprehensive list of supplements which studies have shown can reduce intestinal permeability is found in this thread.
Irritable bowel syndrome treatments. If you have been diagnosed with IBS, there is evidence that bacterial infection may play a causal role, because a 2 week course of the antibiotic rifaximin can put IBS into remission for 3 months.1 A rifaximin is a unique antibiotic that is not absorbed into the body, and so remains concentrated in the intestines.

Note that IBS can be caused by the intestinal protozoan parasites Giardia lamblia and Blastocystis hominis. For Giardia lamblia, a single dose of the antiprotozoal drug tinidazole is an effective treatment.1 Some Blastocystis hominis eradication protocols are detailed in this thread post.

For symptomatic relief of IBS, peppermint oil capsules, probiotics, and for IBS with diarrhea (IBS-D) the over-the-counter drug loperamide can help. The low FODMAPs diet can be effective.
Small intestine bacterial overgrowth (SIBO) treatments. For hydrogen-predominant SIBO, the antibiotic rifaximin 600 to 1600 mg daily for 10 days is effective (higher doses have greater success).1 Rifaximin is a unique antibiotic which remains in the intestines (it is not absorbed into the body). Rifaximin actually increases populations of friendly bacteria like Lactobacillus and Bifidobacterium in the colon,1 and does not lead to bacterial resistance.1

Methane-predominant SIBO is harder to treat, but rifaximin 400 mg three times daily plus metronidazole 400 mg three times daily for 10 days can be used.1 Metronidazole helps kill the methane-producing archaea. Alternatively rifaximin 400 mg three times daily plus neomycin 500 mg twice daily for 10 days is effective.1 Neomycin however can harm kidneys, ears (ototoxic), brain and nervous system, and can cause loss of muscle function.1 Having gastrointestinal inflammation may increase the risk of getting toxic effects from neomycin.1

One study found that a physician's elemental diet (to starve the bacteria) for two weeks was highly effective at eradicating SIBO.1 More info here. Homemade elemental diet recipe here.

Herbal treatment of SIBO was shown in one study to be just as effective as antibiotic treatment.1 Herbs used for SIBO include allicin, neem, berberine, oregano oil, cinnamon, cloves, olive leaf extract and red thyme essential oil. Often several herbs are taken together. A study found that the essential oils of cinnamon and winter savory were strongly effective against gut bacteria; aniseed, asafoetida, clove, oregano and thyme essential oils were also good.1

Allicin may be useful for methane-predominant SIBO, as it decreases populations of the archaea in the gut which produce the methane.1 Clove, garlic and oregano essential oils reduce methane production.1

Dietary treatments that reduce food sources for bacteria can bring SIBO under control. Such diets include: the specific carbohydrate diet, the GAPS diet, and the low FODMAP diet. See: Dietary Treatments.

Once the bacterial overgrowth in the small intestine is brought under control by treatment, it is usually necessary to adopt a prevention strategy to stop SIBO from reappearing. Without adopting a prevention strategy, recurrence of SIBO is common.

Prokinetics (these stimulate motility — the movement of food through the digestive tract) help prevent SIBO recurrence. Prokinetics for SIBO include: low-dose naltrexone at bedtime, 2.5 mg for diarrhea SIBO or 5 mg for constipation SIBO; low-dose erythromycin 50 mg at bedtime; prucalopride 0.5 to 1 mg at bedtime; or a natural option is ginger root 1 gram at bedtime.1
Chronic bacterial intoxication syndrome (CBIS) and kidney dysbiosis treatments. If your high-sensitivity urine test is positive for one or more species of bacteria, and if Dr Markov finds your symptoms are characteristic of CBIS, he may prescribe you his autovaccine treatment.

An autovaccine is a vaccine which is custom manufactured from the patient's own bacteria (in this case, the bacteria detected in the urine). These bacteria are inactivated (killed) and made into a vaccine. The autovaccine stimulates the immune system to fight the bacteria in the kidneys. Dr Markov's published study states that the autovaccine therapy provided by the Markov Clinic permanently cures 93% of ME/CFS patients; but it usually requires 2 to 3 years of autovaccine therapy to reach the cured state.1 
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
Low T3 syndrome treatments. If you have subclinically low T3, the study which first identified low T3 syndrome in ME/CFS patients suggests that taking supplemental T3 as the drug liothyronine as well as supplemental iodine might be helpful (though the authors state that their study first needs confirmation). Dr Kent Holtorf specializes in treating hormonal irregularities in ME/CFS, and has a theory on why T3 can be low in ME/CFS.
Postural orthostatic tachycardia syndrome (POTS) treatments. There are a number of drugs that can help treat POTS, but some drugs may work better for specific subtypes of POTS. There are two classification schemes for POTS subtypes, Dr Grubb's scheme and Dr Stewart's scheme:

Dr Blair Grubb divides POTS into 3 subtypes (according to their causes and characteristics):1
  • Neuropathic POTS — aka partial dysautonomic POTS. Caused by partial loss of autonomic nerves, often due to viral infection.
  • Hyperadrenergic POTS — due to high levels of norepinephrine in the blood. May cause anxiety, tremor and an urge to pass urine on standing. Hyperadrenergic POTS can be diagnosed if the Valsalva maneuver causes a high blood pressure spike and flushing when standing.1 There is also often an increase in systolic blood pressure on standing.1
  • Flushing POTS — involves upper torso and facial flushing for unknown causes.
Dr Julian Stewart divides POTS into 3 subtypes (based on clinical findings):1
  • High-flow (hyperkinetic) POTS — involves increased blood flow pumped through the heart in an attempt to compensate for the inability to constrict arteries resulting from low norepinephrine (a vasoconstrictor). High-flow POTS involves blood pooling in the legs. High-flow POTS closely corresponds to neuropathic POTS.
  • Low-flow (hypokinetic) POTS — involves reduced blood flow, low blood volume, and constricted arteries. Low-flow is characterized by general pallor and cool skin, and there may be acrocyanosis (a blue or purple coloring of hands and feet).1 Causes of the constricted blood vessels in low-flow POTS include:1 elevated angiotensin II, and norepinephrine transporter deficiency (the latter is similar to hyperadrenergic POTS).1
  • Normal-flow POTS — blood flow is normal.
Dr Stewart found losartan (an angiotensin II receptor blocker) treats low-flow / hyperadrenergic POTS.1

POTS can be treated with vasoconstrictors to decrease blood pooling such as midodrine, pyridostigmine, ephedrine and theophylline; blood volume enhancing drugs such as fludrocortisone 0.1 to 0.2 mg daily, desmopressin and propranolol; intravenous saline is often reported as effective. Increasing salt or sodium intake (POTS doctors recommend anything between 3 and 15 grams of salt daily) in combination with drinking at least 2 liters of water daily may help. Exercise benefits POTS (but exercise may not be possible in more severe ME/CFS).

Some patients with POTS also have mast cell activation syndrome (MCAS), and these patients may be made worse by beta-blockers such as propranolol.1

More info: POTS - What Helps. Note: different doctors may use subtype names to mean different things.
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 treatments above), beta blockers such as propranolol, fludrocortisone (Florinef), and licorice root.

3RD ROUND: Tests for Less Common Infections
This third round of tests focuses on rarer microbial causes and contributory factors of chronic fatigue syndrome.

Possible Causal Factor Tests and Results Interpretation
Herpes Simplex Virus 1 and 2

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

► Go to HSV treatments
HSV 1 & 2 IgG antibodies. LabCorp, Quest. UK/EU: ArminLabs.
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

► Go to HHV-7 treatments
HHV-7 IgG antibodies.

Antibody tests: Quest. UK/EU: ArminLabs.

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

► Go to 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

► Go to 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, M. fermentans, M. hominis, M. penetrans. By contrast, such infections are detected in the blood of only 10% of healthy adults.

ME/CFS patients infected with more than one mycoplasma species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasma 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.

► Go to Mycoplasma treatments
Mycoplasma pneumoniae 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 higher.1 2

IgM/IgG: LabCorp, Quest. UK/EU: ArminLabs.

A persistent lingering dry cough / tickly throat is a common sign of a mycoplasma pneumonia infection.1
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.

► Go to 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.

A new much more sensitive Bartonella test called the droplet digital PCR (ddPCR) test is available from Galaxy Diagnostics for $650.
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.

► Go to 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 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.

► Go to 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.

► Go to West Nile virus treatments
West Nile virus antibodies.
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

► Go to Ross River virus treatments
Ross River virus antibodies.

3RD ROUND: Treatments for Less Common Infections
In the light of the results of the third round of tests, the following treatments can be considered:

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.

The drug sodium phenylbutyrate has antiviral effects against HSV in vivo in mice.1
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 in this thread.
Coxiella burnetii treatment. For Coxiella burnetii infection, doxycycline 100 mg daily for 3 months can lead to significant improvements in symptoms.1
Giardia lamblia treatment. For Giardia lamblia infection (giardiasis), 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 Lauric acid in coconut oil has some useful efficacy against Giardia.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. For 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. Bartonella infection (bartonellosis) can be treated with antibiotics such as azithromycin, but most cases of cat scratch disease (from Bartonella henselae) resolve without treatment.1
Babesia treatment. Babesia infection (babesiosis) is treated with a combination of the anti-malarial drug atovaquone and the antibiotic azithromycin for 7-10 days; or alternatively the anti-malarial drug quinine and the antibiotic clindamycin for 7-10 days.1 This treatment is extended to 6 weeks in people with relapsing disease.1
Brucella treatment. Brucella infection (brucellosis) 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 for Rarer Causes or Contributory Factors
This fourth set includes rarer causes or contributory factors of chronic fatigue syndrome.

Possible Causal Factor Tests and Results Interpretation
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 And one study found 5% of ME/CFS cases followed hepatitis B vaccine.1

Dr Osamu Hotta in Japan has found that vaccine-triggered ME/CFS-like illnesses involve chronic inflammation of the nasopharynx, and once this is treated, it cures or greatly improves the illness.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/autoinflammatory syndrome induced by adjuvants (ASIA).1 Adjuvants that precipitate ASIA include: aluminum hydroxide, squalene and silicone.1

► Go to vaccination trigger treatments
A patient survey run by Dr Charles Shepherd found the vaccine most commonly linked to triggering ME/CFS is hepatitis B. The survey also found influenza, BCG, tetanus, meningitis, MMR, polio, hepatitis A and typhoid vaccines are linked to triggering ME/CFS.1

The US Federal Court ruled hepatitis B vaccine caused ME/CFS in one patient, and awarded $1.1M plus lifetime medical expenses.1

Vaccines with an aluminum hydroxide adjuvant have been shown to occasionally trigger macrophagic myofasciitis (MMF), which has similar symptoms to ME/CFS.

Although you get more aluminum from your diet than you do from a vaccine, the aluminum hydroxide from a vaccine creates insoluble microparticles which have long-term persistence in immune cells, and this may help explain how vaccines trigger ME/CFS or MMF.1

It should be possible to distinguish between vaccine-triggered ME/CFS and MMF by the timescale of onset: when ME/CFS is triggered by a vaccine, full-blown ME/CFS very often appears within days of the vaccination; whereas the average time between vaccination and the onset of macrophagic myofasciitis symptoms is 7 months, according to this paper, and the very fastest onset the authors came across was two weeks. So if your symptoms appeared within days of vaccination, it's likely ME/CFS not MMF.
Physical Trauma (Like a 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. Concussion causes changes in the gut microbiome,1 and this perhaps might explain how PCS arises, since ME/CFS is linked to the microbiome.

► Go to 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 advisable. 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.

Pituitary hormones include human growth hormone (HGH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and others. Hypopituitarism from TBI can lead to a deficiency in one or more of these hormones.

The symptoms of HGH deficiency are listed in this thread post. TSH deficiency causes hypothyroidism, with symptoms such as fatigue, cold sensitivity, depression, and many others. ACTH deficiency causes symptoms like fatigue, weight loss, lack of appetite, low mood, increased thirst and urination, and others.

Physical trauma may also lead to various types of spinal injury or brainstem conditions which can cause ME/CFS-like symptoms. These conditions include craniocervical instability and Chiari malformation. See the CCI/AAI section.
Craniocervical instability (CCI), Chiari Malformation & Related Spinal and Brainstem Physical Dysfunctions

A number of mechanical conditions which affect the top of the spine, skull and brainstem can cause ME/CFS symptoms, as well as the symptoms of POTS. These conditions include CCI, AAI, Chiari malformation, cervical spinal stenosis and others.

Surgery to fix these conditions can lead to full remission of ME/CFS, or result in major improvements. Two ME/CFS patients Jeff Wood and Jen Brea who had corrective neurosurgery for CCI/AAI were cured of their ME/CFS. Jeff's story in this thread post and on his website Jen's story in this thread.

When over 60 ME/CFS patients were tested in 2018/2019 for CCI, AAI, Chiari or cervical spinal stenosis, around 75% were found to have this condition (though this figure may not be representative of the general ME/CFS patient population, due to biases such as self-selection for testing based on having CCI symptoms).1

The results of a detailed survey on ME/CFS patients with CCI, AAI and related conditions found in this thread.

More info on CCI and related conditions here, in this thread and this thread. Facebook group for ME/CFS patients on the CCI journey.

There are only a few neurosurgeons in the world who are able to diagnose and surgically treat CCI/AAI. Some of the top ones are Dr Paolo Bolognese, Dr Vicenç Gilete and Dr Fraser Henderson.

► Go to CCI/AAI treatments
Craniocervical instability (CCI) — is a weakness and instability of the connection between skull and spine caused by lax ligaments. This instability is located where the skull meets the top C1 vertebra of the spine. CCI may lead to deformation or compression of the brainstem, upper spinal cord and cerebellum, which can then lead to ME/CFS-like symptoms.1 CCI can be caused by physical trauma, can be congenital, can be caused by infection, or can appear in certain diseases such as rheumatoid arthritis and Ehlers-Danlos syndrome.

Diagnosing CCI/AAI requires an MRI or CT scan of the cervical spine (not the head). The diagnostic process is described here. Some CCI neurosurgeons such as Dr Gilete and Dr Henderson will ask you to send them an upright MRI scan of your cervical spine, with neutral (head looking straight ahead), flexion (looking down), extension (looking up) and rotational (head looking left and right) images. Places which offer upright MRI scans shown on this map. Whereas Dr Bolognese asks you to send a supine MRI of the cervical spine with the head in the neutral position only.

Most patients with CCI, AAI, Chiari or cervical spinal stenosis will have cervical medullary syndrome (CMS) symptoms. So having several of these CMS symptoms is suggestive of CCI and related conditions. Some patients with CCI etc observe a change in their ME/CFS symptoms, or a sudden inability to breathe, according to the position they hold their head and neck in (see this thread post).

Atlantoaxial instability (AAI) — is a structural instability of the connection between the C1 and C2 vertebra of the spine. AAI and CCI often occur together.

Chiari malformation — where brain tissue is pushed into the spinal canal, due to a skull which is too small or misshapen and thus squeezes the brain and forces it downwards. This may cause ME/CFS-like symptoms, as well as multiple sclerosis-like or fibromyalgia-like symptoms. Chiari is usually a congenital condition, but asymptomatic congenital Chiari can be worsened by a physical trauma such that symptoms may then manifest.1 Patients with Chiari malformation may also have craniocervical instability. Chiari malformation is sometimes found in Ehlers-Danlos syndrome. More info here.

Cervical spinal stenosis — where the spinal canal becomes too narrow, which can put pressure on the nerves, leading to ME/CFS-like symptoms. Cervical spinal stenosis can be caused by a physical trauma to the spine (or just caused by general wear and tear). Surgical treatment of cervical spinal stenosis can lead to resolution of ME/CFS symptoms.1

Syringomyelia — a fluid-filled cyst which appears within the spinal cord, and compresses the spinal nerves, which may result in ME/CFS-like symptoms.1 A trauma to the spine can sometimes cause a syringomyelia to form some time later. Syringomyelia can be treated surgically.

Tethered cord — where the spinal cord gets "stuck" to a structure within the spine, such as dura, scar tissue from a previous operation, a bony spicule or even a tumor. This condition may cause ME/CFS-like symptoms. Tethered cord can be caused by physical trauma, or can be congenital. Tethered cord is often found in those with Chiari malformation and CCI/AAI. However, a tethered cord is usually not identified prior to CCI/AAI surgery, because when someone has CCI/AAI, their cord has more slack. Once the CCI/AAI is corrected, the congenitally-tethered cord becomes more apparent. Most most people undergoing CCI/AAI surgery will also have tethered cord surgery.1
Temporomandibular Joint Dysfunction & Jaw Misalignment

Temporomandibular joint dysfunction (TMJ) involves inflammation and misalignment of the temporomandibular joint (which connects the jawbone 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

► Go to 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 jawbone 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 (a muscle on your face just in front of your earhole) 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.
Jawbone Cavitation Infection
Cases of ME/CFS have occasionally been caused or worsened by infections located within the jawbone (osteomyelitis). Such infections develop inside hollow pockets within the jawbone called cavitations. Cavitations can be left in the jawbone after a tooth extraction, such as a wisdom tooth removal; 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 jawbone cavitations also induce facial pain, they are called NICO lesions.

Jawbone cavitation infections induce the inflammatory chemokine RANTES, as well as FGF-2. Both are linked to systemic disease.1 2 Increased RANTES is found in the jawbone and blood serum of ME/CFS patients.1 This suggests RANTES from jawbone cavitations may play a role in ME/CFS.1 See this thread for more info.

Stories of ME/CFS patients improving after treatment of jawbone cavitations:
Ian's recovery story and also here
Ian's Website
Errol's cavitations and root canal story
Dukey's recovery story.

Facebook group here.

► Go to jawbone cavitation infection treatments
Jawbone infections can be hard to detect, as they often cause only very minimal local symptoms. Yet a local infection within the jawbone can cause a condition symptomatically identical to ME/CFS.

Sometimes a jawbone cavitation infection may cause chronic facial pain, but such facial pain is not always present. Jawbone infections may also cause a sour bitter taste in the mouth, causing bad breath or even gagging.

A simple test for a jawbone infection is applying pressure with a finger on the gums to the jawbone beneath; if any area feels painful, this indicates a possible jawbone infection (though this test will not always detect a jawbone infection).

A MRI STIR scan is an accurate way to detect jawbone infections.

The Cavitat and CaviTAU ultrasound scanners are the best and most effective way to detect jawbone cavitations.

Panoramic dental X-rays can detect jawbone cavitations, but are not very reliable, and they require skilled interpretation by dentists experienced in detecting cavitations (very few dentists have this experience). Ordinary MRI scans or CT scans are not good at detecting jawbone cavitations.

More info on the diagnosis and treatment of jawbone cavitation infections is given here:
The Appearance of NICO Lesions
Diagnosis and Treatment of Cavitational Lesions

Jawbone 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 jawbone cavitation infections include: Munro-Hall Clinic (Bedford), Dr Elmar Jung Dental Clinic (Southampton).
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

► Go to 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 for more information.

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.

► Go to 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 in this thread post.
Toxoplasma gondii

Toxoplasma gondii is an intracellular protozoan parasite that  causes toxoplasmosis. It is usually caught from undercooked meat or cat feces.

In rare cases, infection with Toxoplasma gondii can lead to ME/CFS.1

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Dr Uwe Auf der Strasse's website is an excellent resource on chronic active toxoplasmosis symptoms, testing and treatment.

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 2 Silicone is known to affect the immune system (it is used as an immune stimulating adjuvant in vaccines for this reason).

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

More info on silicone illness here.
Pesticide Exposure

Chronic exposure to significant amounts of organophosphate pesticides such as malathion have been linked to triggering ME/CFS.1 2 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.

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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-parasitic 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 exposure link to ME/CFS
Pesticide Routes of Exposure – PAN UK
Ciguatoxin Exposure

Ciguatoxin exposure causes the disease of ciguatera, which can later sometimes lead to a protracted ME/CFS-like illness,1 2 which Dr Ritchie Shoemaker states is a case of CIRS (chronic inflammatory response syndrome). CIRS is detailed in the toxic mold exposure 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.

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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.
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.

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Radiotherapy or Chemotherapy

When undertaken as a cancer treatment, either can lead to chronic fatigue syndrome soon afterwards.1

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Ionizing Radiation

Large doses of ionizing radiation can cause ME/CFS-like symptoms, but outside nuclear accident events like Chernobyl, nobody is really exposed to such high doses.

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More info: National CFIDS Foundation — Ionizing Radiation and CFIDS/ME
Emotional/Psychological Stress

Though ME/CFS is usually precipitated by viral infection, several studies found that some ME/CFS patients experienced major chronic stress (such as from divorce, bereavement or serious financial woes) in the year leading up to the development of their ME/CFS.1 2 3 4

While some dubious psychiatrists have used this stress connection to promote their view that ME/CFS is an "all in the mind" psychogenic condition, a more sensible biological explanation is based on the fact that chronic stress weakens antiviral immunity,1 2 which then gives an acute viral infection the opportunity to enter into tissue compartments such as the brain that it may not otherwise breach.

Chronic stress weakens immunity by raising the hormone cortisol, which in turn suppresses antiviral Th1 immunity,1 and decreases the T-cell response.1

Analogously, Dr John Chia discovered that corticosteroid drugs given during acute viral infection are a major risk factor for ME/CFS (see box below).

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While it is feasible that experiencing major chronic stress just before catching your ME/CFS-triggering virus may, as a result of the immunosuppressive effects of stress, have allowed the virus to insinuate itself more deeply into your body, thereby causing ME/CFS, once the stressful events are over and long past, it seems unlikely that this stress still remains in your mind.

So for most people it is not likely that a period of chronic stress from years ago has any effect on your current state of ME/CFS.

However, in some people, it is conceivable that prior stress locks or etches itself into the mind, leading to a state of unconscious ongoing mental stress, even though the stressful events are long past. Past stress is known to have consequences (it is the basis of post-traumatic stress disorder for example). Thus hidden locked-in stress possibly might explain why in rare cases, ME/CFS patients benefit from a psychological therapy which tries to identify and defuse these unconscious mental stresses.

Thus if your ME/CFS appeared after a period of major chronic stress, and if you feel that this stress may have somehow etched itself into your mind, you might consider psychological therapy.

But outside of these infrequent cases, there is no evidence to suggest that the condition of ME/CFS is maintained by psychogenic factors.
Corticosteroids Given During 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

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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.

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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 in this thread post.
Raymond Perrin's website here.

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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 you have ME/CFS. More info about Perrin point testing in this thread.

4TH ROUND: Treatments for Rarer Causes or Contributory Factors
In the light of the results of the fourth round of tests, the following treatments may be of use:

Vaccination-triggered ME/CFS treatments. Dr Osamu Hotta in Japan devised a simple and effective treatment for vaccine-triggered ME/CFS-like illnesses. Dr Hotta discovered that ME/CFS-like illnesses triggered by HPV and other vaccinations often involve chronic inflammation in the nasopharynx (nasopharyngitis). The nasopharynx is an area of mucous membranes located just above the back of the throat. Once this inflammation is treated by dabbing on an anti-inflammatory zinc chloride solution to the nasopharynx, this cured the illness in 25% of cases, and substantially improved it in 56% of cases.1 2 3 4 Dr Osamu Hotta details his research in this video.

ME/CFS triggered by vaccination may also 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.
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.
Treatments for craniocervical instability, atlantoaxial instability and related conditions. Surgery is the main treatment for CCI/AAI and related conditions.
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. Dr Amir charges £10,000 for consultation, manufacture of the custom dental appliance and readjustments.
Jawbone infection treatments. If you suspect you may have a jawbone cavitation infection, you may want to seek help from a dentist or maxillofacial surgeon who specializes in diagnosis and treatment of jawbone cavitations.
Sinusitis treatments. Antibiotics may help for bacterial sinusitis, otherwise corticosteroid nasal sprays can help reduce the sinus and nasal inflammation. Nasal irrigation to flush out the sinuses can be a useful treatment for sinusitis; the inversion technique nasal irrigation is an advanced and more effective means of sinus flushing. Avoiding dairy products can improve sinusitis. Surgery to enlarge the sinus openings can be considered when all else fails.
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.
Toxoplasma gondii treatments. Dr Uwe Auf der Strasse treats chronic active toxoplasmosis with a combination therapy for about 3 to 4 weeks, or in severe cases, up to 10 weeks.

The combination treatment involves three drugs: pyrimethamine (Daraprim) 25mg twice daily, which starves the parasite of folate; calcium folinate 6 mg daily (it is vital to take this folinic acid supplement while taking pyrimethamine); and the antibiotic clindamycin 600 mg twice daily.
Silicone breast implant leakage treatments. Symptoms caused by leakage of silicone from breast implants usually improve on removal of the breast implants.1
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 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 likely to help, except in severe acute exposure.
Ciguatoxin poisoning treatments. The anti-inflammatory effects of herb Vitex trifolia are useful for treating ciguatera poisoning.1
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 infection in particular, as well as testing for the other viruses tailed in the 1st round tests section, can be considered.
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.
Emotional/psychological stress treatments. On rare occasions, some patients find psychological therapies such as Reverse Therapy have helped improve their ME/CFS. Here is the blog of an ME/CFS patient who got much better after such therapy. However, be cautious about cult psychological therapies like the Lightening Process, which may "brainwash" you into ignoring your ME/CFS symptoms, or indoctrinate you into thinking your ME/CFS has improved, when in fact objectively you are no better.
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.
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 acquiring 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.
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).