News And Educational Articles

Cytomegalovirus

Cytomegalovirus (CMV) is part of the Herpes family of viruses.  There are eight separate viruses within this family: Herpes simplex 1 and 2 (HV 1, HV 2), Varicella (HV 3), EBV (HV 4), Cytomegalovirus (HV 5), Herpes virus 6 (HV 6), Herpes virus 7 (HV 7), and Kaposi sarcoma-associated virus (HV 8). (1)  HV1 and 2 are most commonly associated with oral and genital herpes.  Varicella causes chickenpox and shingles and CMV causes CMV mononucleosis, which is similar to EBV mononucleosis but is often less severe. HV6 and HV7 are most commonly associated with roseola infantum.  HV8 is not a known cause of acute illness but may cause Kaposi sarcoma and AIDS-related non-Hodgkin lymphomas. (1)

Infection and Transmission

All herpes viruses can remain latent within the body and can reactivate; if the virus reactivates, it can be spread to others. People can also be infected by a different strain of the CMV virus than the strain of a previous infection. (2)   “In the United States, nearly one in three children are already infected with CMV by age five and over half of adults by age 40 have been infected with CMV.” (2)  Merck manual has those rates even higher, indicating that “60 to 90% of adults have CMV infection resulting in lifelong latent infection.” (4)

CMV spreads primarily through body fluids, including blood, saliva, urine, tears, semen, vaginal fluids, and breast milk (2, 3).  CMV is spread from an infected person by:

  • from direct contact with saliva or urine, especially from babies and young children;
  • through sexual contact;
  • from breast milk to nursing infants; and
  • through transplanted organs and blood transfusions.

A woman who is infected with CMV can pass the virus to her developing baby during pregnancy. Women may be able to lessen their risk of getting CMV by reducing contact with saliva and urine from babies and young children because the saliva and urine of children with CMV have high amounts of the virus. A pregnant woman can avoid getting a child’s saliva in her mouth by, for example, not sharing food, utensils, or cups with a child. Also, she should wash her hands after changing diapers. These cannot eliminate her risk of getting CMV, but may lessen the chances of getting it.

Symptoms of Acute Infection

According to Mayo clinic, CMV “rarely causes problems in healthy people” (3) and initial CMV infection may cause no symptoms at all.  Symptoms of a CMV infection can include fever, sore throat, fatigue, muscle aches, and swollen glands, and as such, may be referred to as CMV mononucleosis, given the similarity in symptoms with Epstein-Barr virus infection.  (2, 3)   According to Mayo Clinic, CMV may be less likely to cause swollen glands or enlarged spleen than EBV (3).  Like an EBV infection, CMV infection can also cause hepatitis. (2)

The main issues are for pregnant women or people who are immunocompromised.  In pregnancy, the virus can cross the placenta and infect the fetus, causing “brain, liver, spleen, lung, and growth problems” (2), abortion, stillbirth, or post-natal death (4). The most common health problem in babies born with congenital CMV infection is “hearing loss, which may be detected soon after birth or may develop much later in childhood.” (2) Perinatal infections can also occur during or soon after birth can also be an issue. (3) “Babies with congenital CMV who are sick at birth tend to have significant signs and symptoms, including:

  • Premature birth
  • Low birth weight
  • Yellow skin and eyes (jaundice)
  • Enlarged and poorly functioning liver
  • Purple skin splotches or a rash or both
  • Abnormally small head (microencephaly)
  • Enlarged spleen
  • Pneumonia
  • Seizures” (3)

In the immunocompromised, the infection can affect eyes, lungs, liver, stomach, intestines, and brain and can be much more serious, including being fatal. (3)

Chronic Infection Concerns

Most of the sources on CMV infection indicate that long-term complications occur in congenital infections and immunocompromised patients, and that “rare complications for healthy adults include problems with the digestive system, liver, brain and nervous system”. (3) However, emerging research is showing that CMV infection may be a significant contributor to cardiovascular disease, diabetes and metabolic syndrome, autoimmune diseases, and cancer.

Cardiovascular Disease

A nationally representative population-based study from 1999 to 2002 found that being seropositive for a CMV infection was associated with high blood pressure in women. (5)  This meta-analysis included “three studies involving 9657 patients…and the results showed a significantly increased risk of EH (essential hypertension) in patients with CMV infection.” (6)  The authors concluded that the association was significant to say that “CMV infection is a possible cause of EH.” (6)  Three other studies from 2009, 2016, and 2017 found:

  • “CMV infection is a risk factor for increased arterial blood pressure, and is a co-factor in aortic atherosclerosis” and contributes to the production of pro-inflammatory mediators in the body. (7)
  • “CMV infection is associated with an increase in SBP (systolic blood pressure) in individuals at age 70 years. The magnitude is comparable to environmental variables such as obesity, diabetes or high salt intake. This is the first evidence to show that a chronic infection may be an important determinant of blood pressure and could have significant implications for the future management of hypertension.” (8)
  • “CMV IgG antibody titers were positively correlated with arterial BP, greater grade of hypertension and hypertensive TOD (target organ damage), and CRP and IL-6 levels. In the Han Chinese population, high CMV IgG titers are associated with the progression of hypertension and hypertensive TOD. CMV IgG titer >4.25 U could be an independent predictor of hypertension and progression of hypertension, while that >4.85 U could be an independent risk factor for hypertensive TOD. The underlying mechanism may be largely mediated by chronic inflammation.” (9)

CMV infection may also be linked to cardiovascular disease and “high levels of antibodies against CMV seem to be associated with clinically manifested atherosclerotic disease, which may indicate repeated reactivation of latent infection in many of these patients.” (10) A 2010 study found the “proinflammatory influence of persistent CMV on the microvasculature, and suggest that CMV infection enhances microvasculature susceptibility to both inflammatory and thrombogenic (clot forming) responses caused by hypercholesterolemia (high cholesterol). (11)

Diabetes and Metabolic Syndrome

A 2012 study showed that “adults ages 85 and over who were infected with cytomegalovirus were about twice as likely to have Type 2 diabetes compared with those not infected.” (12) The authors stated that their results indicated an association, not necessarily a causation, and that their results may not apply to other populations.

A 2017 report looked at extremely obese women and women of normal weight, all of whom were positive for CMV. Findings indicated women positive for CMV were more likely to develop metabolic syndrome than women who were negative. (13) Additionally, the extremely obese women were less likely than women of normal weight to develop metabolic syndrome and the authors stated that “the key initiator of metabolic syndrome is chronic, low-grade inflammation, rather than obesity per se… (and) consequently, it is worth exploring whether alternative sources of chronic, low-grade inflammation, other than obesity, are contributing to the burden of [metabolic syndrome].” (13)

Autoimmune Diseases

Literature suggests a causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA). (14) Asian scientist reported in 2016 that CMV infection may cause autoimmune diseases by destroying natural killer cells. The CMV induces an antibody that also targets NK cells, and the “reduction of NK cells is characteristic of a bunch of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus and primary Sjogren’s syndrome.” (15) CMV infection can also aggravate autoimmune mediated neuro-inflammation and demyelination in MS (16) and a 2017 study indicated that “CMV-DNA copy numbers and concurrent infections are predictors of in-hospital mortality in CMV-infected patients with autoimmune diseases.” (17)

Cancer

CMV has also been considered a factor in the development of cancer.  A 2016 study “suggested a statistically association between the virus infection and an increased risk of colorectal cancer” (18) and a 2014 study from the USC School of Dentistry identified CMV as a cause of the most common salivary gland cancers.” (19) Other studies identify CMV infection as having a “modulatory effects on tumours, increasing their malignancy. Manipulation of the host cell cycle as well as the immune response may promote the replication and propagation of the virus and as a consequence of that interruption of the normal checks that block cancer growth.” (20)  There are many questions still surrounding the role of CMV in cancer and more research needs to be done to understand the connections and associations that have been seen so far.  “In the last decade, multiple investigators have identified HCMV infection specifically in human malignancies including malignant glioma, colon cancer, breast cancer, prostate cancer, medulloblastoma, salivary gland (mucoepidermoid) carcinoma, neuroblastoma, and rhabdomyosarcoma. Considerable controversy exists as to whether a) HCMV infection is actually present in these malignancies, and b) if present, whether HCMV is involved in the initiation and/or promotion of the tumors. Should HCMV persistently infect various human cancer types, it is possible that multiple viral-driven oncogenic mechanisms may potentially be involved.” (21)

In the nervous system, CMV can cause encephalitis and may be associated with Guillain-Barre syndrome. (22) CMV can also cause symptoms in the digestive tract, including ulcers, diarrhea, intestinal bleeding and gastroenteritis/colitis, as well as symptoms in the lung, including shortness of breath, pneumonia, and low oxygen. (23) Many of the reports of these symptoms are from immunocompromised patients; however, they provide information about the body systems most affected by the virus, possibly with less severe manifestations in immunocompetent people.

This handout is in no way a full review of the literature on the effects of CMV infection.  However, given the growing research showing associations and/or potential causes between CMV and these major conditions, the complications or long-term effects of CMV infection and reactivation need to be taken more seriously even for otherwise “healthy” patients.

Diagnosis

Diagnosis of acute CMV infection is based on symptoms and signs and bloodwork.  Often patients present with symptoms of mononucleosis (often less sore throat than EBV infection) but have a negative monospot test. (4)  Antibodies specifically for CMV can be tested to identify possible CMV infection.  A complete blood count may also show atypical lymphocytes; it is important to know that “atypical lymphocytes may also be present in HIV or CMV infection, hepatitis B, influenza B, rubella, or other viral illnesses… however, very high atypical lymphocyte counts are typically seen only in primary EBV and CMV infection.” (24)  Because CMV can also cause elevated liver enzymes, blood testing for hepatitis viruses may also need to be done. (4)

Treatment

Treatment of CMV needs to be assessed based on a patient’s current symptoms, test results, and concerns for possible development of future conditions linked to CMV.  According to Western medicine, there is no treatment available for CMV infection except for the use of a few specific antivirals for severe infections in in babies and for the immunocompromised.  (2, 4)  Most sources also say that no treatment is needed for healthy adults.  However, I am very concerned about the developing body of research linking CMV as a potential association or causative factor for cardiovascular disease, metabolic syndrome and diabetes, many common autoimmune diseases, and cancer.  These diseases occur due to a combination of many different genetic and environmental factors.  Some factors, such as our genes, we cannot change.  There may be other factors medicine hasn’t identified yet.  Since these are areas we cannot treat, I look to those known environmental factors that are significant risk factors.  By reducing their impact, we can hopefully prevent future disease or reduce disease activity for those patients already diagnosed with autoimmune conditions.

Although most adult infections are due to reactivation of a previous infection,  preventative measures can be taken to avoid infection, including washing hands thoroughly and often, avoiding contact with body fluids or sharing food or drinks, cleaning toys and countertops, and practicing safe sex. (3)

Naturopathic medicine has many options for treating CMV both in terms of general anti-virals and options specifically designed for CMV.  Levels of immune-essential nutrients, such as vitamin A, vitamin D and zinc, can be optimized. Monolaurin is a byproduct of coconut oil and is commonly used as a general anti-viral.  Lysine, which is often used to treat herpes simplex outbreaks, can also be used for CMV, as can colostrum for patients who do not have issues with dairy.  There are numerous herbs, including olive leaf, garlic, goldenseal, Echinacea, and grape seed, and mushrooms, including cordyceps, turkey tail, shiitake, and lion’s mane, that can be used individually or in combination formulas.  Gemmotherapy preparations of several herbs are designed specifically to treat intra-cellular viruses, and essential oils can be added to herbal combinations.   Treatments can also include supporting the T-regulatory cells of the immune system, including probiotics, fish oil, vitamin D, and glutathione.

When using any of these therapies, it is important to start with low doses and increase slowly to patient’s tolerance.  Many people discuss “die-off” reactions with Lyme disease or candida overgrowth, and the same may be said for CMV infections.  As such, a complete plan would also include supports for detoxification and elimination, and would balance and rotate any anti-viral therapies.

Because these anti-virals are generally safe and well-tolerated, and the impacts of the associated diseases can be devastating, this is one situation where I personally err on the side of treatment, especially in cases where patients have very high antibody levels.  My hope is that we can provide safe and relatively inexpensive treatment that could prevent a future autoimmune condition by treating a potential cause before symptoms arise.

Sources

  • https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/overview-of-herpesvirus-infections
  • https://www.cdc.gov/cmv/overview.html
  • ttps://www.mayoclinic.org/diseases-conditions/cmv/symptoms-causes/syc-20355358
  • https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/cytomegalovirus-cmv-infection
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388091/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010589/
  • http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000427
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027953/
  • http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181440
  • https://www.sciencedirect.com/science/article/pii/S1198743X14636120
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947306/
  • https://www.livescience.com/22749-type-2-diabetes-cytomegalovirus-infection.html
  • https://www.healio.com/endocrinology/obesity/news/in-the-journals/%7B3de0d356-aa04-47c5-bd74-e673337f75e2%7D/obesity-influences-relationship-between-cmv-infection-metabolic-syndrome-in-women
  • https://www.hindawi.com/journals/bmri/2014/472978/
  • asianscientist.com/2016/04/in-the-lab/human-cytomegalovirus-linked-autoimmune-disorders-peking-uni-china/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428769/
  • http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181590
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363545/
  • https://dentistry.usc.edu/2011/11/14/common-virus-conclusively-identified-as-cancer-causing-oncovirus-ostrow-school-of-dentistry-researchers-pinpoint-cytomegalovirus%E2%80%99-central-role-in-salivary-gland-cancer/
  • https://www.quora.com/What-is-the-relationship-between-cytomegalovirus-CMV-and-cancer
  • https://www.frontiersin.org/research-topics/2636/emerging-role-of-human-cytomegalovirus-in-cancer
  • https://www.ncbi.nlm.nih.gov/pubmed/15319096
  • https://www.medicalnewstoday.com/articles/173811.php
  • https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/infectious-mononucleosis
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