Chronic Infections in Autism Spectrum Disorder Patients
Garth L. Nicolson, PhD and Paul Berns, MD

The Institute for Molecular Medicine, Huntington Beach, California and International Molecular Diagnostics, Inc., Huntington Beach, California

Correspondence:  Prof. Garth L. Nicolson, Office of the President, The Institute for Molecular Medicine, Huntington Beach, California 92647.  Tel: 949-715-5978; Fax: 714-596-3072; Email: gnicolson@immed.org; Website: www.immed.org

Introduction
Although autism patients do not all share the same signs and symptoms, they tend to share certain social, communication, motor and sensory problems that affect their behavior in predictable ways.  They often show repetitive behaviors and develop troublesome fixations with specific objects, and they are often painfully sensitive to certain sounds, tastes and smells [1].  These signs and symptoms are thought to be due to abnormalities in brain function or structure.  In many autism patients there are also a number of other less specific chronic signs and symptoms.  Among these are fatigue, headaches, gastrointestinal and vision problems and occasional intermittent low-grade fevers and other signs and symptoms. 
The cause(s) of Autism are unknown and could involve genetic and metabolic defects, and in some cases the illness could be brought on by heavy metal, chemical or biological exposures.  Such toxic exposures are likely to be different in each autism patient, but there may be some similarities in genetic defects and environmental exposures [2, 3] that are important in patient morbidity (sickness) or in illness progression.  Other chronic illnesses have some of the same chronic signs and symptoms, suggesting that there may be some overlap in the underlying causes of these conditions or at least in the factors that cause illness/morbidity or illness progression.  
Chronic Infections Important in Various Illnesses

The complex signs and symptoms that evolve in many, perhaps even in a majority of chronic illness patients, may be due, in part, to systemic chronic infections (bacteria, viruses, fungi) that can penetrate into various organs, including the central nervous system (CNS).  Such infections often follow acute or chronic heavy metal, chemical, biological (viral, bacterial, fungal infections) or environmental insults or even multiple vaccines that have the potential to suppress the immune system and leave children susceptible to opportunistic infections [2-5].  These illnesses probably evolve slowly over time in a multi-step process that may require multiple genetic defects along with multiple toxic exposures. 

Chronic infections may be an important element in the development or progression of autism.  Such infections are usually held in check by immune surveillance, but they can take hold and become a problem if they can avoid host immunity and penetrate and hide in various tissues and organs, including cells of the CNS and peripheral nervous system.  When such infections occur, they may cause many of the complex signs and symptoms seen in various chronic illnesses [5, 6].  Changes in environmental responses and increased titers to various endogenous viruses as well as bacterial and fungal infections have been commonly seen in chronic illnesses [5, 6].  One type of airborne infection that has received renewed interest of late as an important cause, cofactor or opportunistic infection in various chronic illnesses is represented by relatively primitive classes of bacteria that do not have the usual large, rigid cell walls that characterize most bacteria.  These microorganisms, principally Mycoplasmas and other bacteria (Chlamydia, Coxiella, Brucella, Borrelia, etc.), although not as well known as other agents in causing disease, are now considered important emerging pathogens in various chronic diseases where a majority of patients have evidence of these infections in their blood [5, 6].

Autism patients often show their first signs and symptoms after multiple childhood immunizations [2].  In fact, Rimland [2] noted that the sharp rise in Autism only occurred after the multiple vaccine MMR came into widespread use.  In the U.S. children can typically receive as many as 33 vaccines, a dramatic increase in the use of childhood vaccines over the last few decades.  Such vaccines often contain mercury and other preservatives [3].  Commercial vaccines have also been examined for contaminating microorganisms, and one study found that approximately 6% of commercial vaccines were contaminated with mycoplasmas [6].  Thus we examined the extent of mycoplasmal infections in patients with autism.  We were aided in this examination by data that we already collected on families of Gulf War veterans where there was a high incidence of autism and mycoplasmal infections in their children [8].

Gulf War Illness Family Study—Mycoplasmal Infections

As found in previous studies [10, 11], veterans of the Gulf War with chronic illnesses (Gulf War Illnesses or GWI) exhibited multiple signs and symptoms.  Upon examination, the signs and symptoms of GWI were indistinguishable from civilian patients diagnosed with Chronic Fatigue Syndrome or CFS.  Their children aged 3-12, however, were often diagnosed with autism [8].

Similar to previous studies on GWI patients [10, 11], 45 of 110 patients or ~42% in our family study had mycoplasmal infections (Figure 1) , and almost all of these (37 out of 45 or ~82%) were single infections (one species of mycoplasma) [8].   M. fermentans was found in ~85% of these single infection cases (Figure 2).  When the few multiple infection cases were examined, most were found to have combinations of M. fermentans plus either M. pneumoniae, M. hominis or M. genitalium (Figure 2).  In contrast, in healthy control subjects only 6 of 70 subjects (8.5%) were positive for mycoplasmal infections, and all of these were single species infections of various types [8].  Comparing GWI patients and non-symptomatic control subjects, there was a significant difference in the incidence of mycoplasmal infections (P<0.001).  However, significant differences in infection incidence or species of mycoplasmal infection between male and female GWI patients or control subjects were not seen in these patient groups [8].  

Figure 1.  Percent incidence of mycoplasmal infections in family members of veterans with Gulf War Illnesses.
In family members of Gulf War veterans with GWI there was evidence of transmission of the illness.  These families were not randomly chosen; they were families in which one or more veteran members were found to be positive for a mycoplasmal infection and one or more family members reported chronic illnesses.  We found that 57 out of 107 (53.2%) of these members from families with one or more Gulf War veteran diagnosed with GWI and with a positive test for a mycoplasmal infection showed symptoms of CFS (and autism or ADHD in their children).  Among CFS-symptomatic family members, most (40 out of 57 or 70.2%) had mycoplasmal infections compared to the few non-symptomatic family members who had similar mycoplasmal infections (6 out of 50 or 12%) (Figure 1).  When the incidence of mycoplasmal infection(s) was compared within families, the CFS-symptomatic family members were significantly more likely to have mycoplasmal infections compared to non-symptomatic family members (P<0.001).  Symptomatic children (mostly diagnosed with autism and other chronic disorders) in these families were also infected with mycoplasmas at high incidence (Figure 1), but this was not seen in aged-matched control subjects (data not shown).  Although some non-symptomatic family members did have mycoplasmal infections (6 out of 50 or 12%), this was not significantly different from the incidence of mycoplasmal infections in control subjects (6 out of 70 or 8.5%) (Figure 1).  Some of these control subjects may be carriers and some may eventually present with CFS or other illnesses related to mycoplasmal infections.

Figure 2. The incidence of various mycoplasma species in Gulf War Illnesses.  All cases of multiple mycoplasmal infections were combinations of M. fermentans.
The mycoplasma infection types were also similar between GWI patients and their autism or CFS-symptomatic family members.  In 45 mycoplasma-positive CFS-symptomatic family members, most (31 out of 40 or 77.5%) had single species infections, similar to the mycoplasma-positive Gulf War veterans (37 out of 45 or 82%).   Most mycoplasma-positive GWI patients as well as mycoplasma-positive family members with CFS or children diagnosed with autism had M. fermentans in their blood (Figure 3).  We did not find differences in the incidence of infection or type of infections between males and females, children versus adults or spouses versus other family members (data not shown).  However, similar to previous reports, the time of onset of CFS illness after the Gulf War tended to be shorter in spouses than other family members, but these differences did not achieve significance [8].

Chronic Infections in Autism Patients

We next examined a small cohort of autism patients in Central California.  This comprised 18 patients aged 3-11 who were diagnosed with autism.  Most of these children had at least one parent with a chronic illness, and the most common diagnosis of adults or adolescents in the same family was CFS or Fibromyalgia Syndrome.  When the autism patients were examined for mycoplasmal infections, twelve children tested positive (66%) for mycoplasmal infections.  However, in contrast to the children of GWI patients who for the most part had only one type of mycoplasmal infection, M. fermentans, or the same infection as their parent with GWI, the Central California group that tested positive for mycoplasmal infections had a variety of different species of mycoplasmas (Figure 4).  We also tested a few siblings without apparent signs and symptoms, and for the most part few had these infections (3 out of 23 subjects or 13%).  Similar results were found in the Gulf War veterans’ families where 12% of non-symptomatic family members had mycoplasmal infections [8].  The finding of a variety of different species of mycoplasmas in autism patients was similar to the results in a number of studies on CFS and FMS patients where multiple infections of various species of mycoplasmas were commonly found [9].

Figure 3. The incidence of various mycoplasma species in family members of veterans with Gulf War Illnesses.  All cases of multiple mycoplasmal infections were combinations of M. fermentans.

Discussion

About one-half of the family members of veterans of the Gulf War with GWI were diagnosed with CSF or a related fatiguing illness, Fibromyalgia Syndrome (FMS) but their symptomatic children were usually diagnosed with autism [8, 10, 11].  At least 50-60% of CFS and/or FMS patients are positive for mycoplasmal infections [5, 6, 9, 12-16].  However, in contrast to mycoplasma-positive GWI patients and their mycoplasma-positive family members diagnosed with CFS or autism, several species of mycoplasmas in addition to M. fermentans were found in civilian CSF and FMS patients from non-military families [12-16].  Similarly, we also found various species of mycoplasma in children diagnosed with autism from Central California. 

Figure 4. The incidence of various mycoplasma species in patients with Autism from Central California.  All cases of multiple mycoplasmal infections were combinations of M. fermentans.

There could be different sources of the mycoplasmal infections found in GWI patients [17].  An important possible source for the mycoplasmal infections found in GWI patients is the multiple vaccines that were administered during the time of deployment to the Persian Gulf.  A strong association has been found between GWI and the multiple vaccines that were administered during deployment [18-20].  Also, Steele [20] found a three-fold increased incidence of GWI in non-deployed veterans who had been vaccinated in preparation for deployment, compared to non-deployed, non-vaccinated veterans, and Mahan et al. [21] found a two-times higher incidence of GWI signs and symptoms in veterans who recalled receiving anthrax vaccinations versus those who thought they had not.  Although the mycoplasmal infections found in GWI patients could have come from several sources, including offensive Biological Warfare attacks [22], we consider the most likely source of the mycoplasmal infections in GWI patients was the multiple vaccines administered during deployment [17].  Indeed, the signs and symptoms that have developed in Armed Forces personnel who recently received the anthrax vaccine are similar to those found in GWI patients.  On some military bases this has resulted in chronic illnesses in as many as 7-10% of personnel receiving the vaccine [23].  Undetectable microorganism contaminants in vaccines could have resulted in illness, and this may have been more likely in individuals with compromised immune systems caused by chemical and other exposures [17].  Similarly, the onset of autism in children from civilian families is also, in some cases, associated with multiple vaccines [2].  

Contamination with mycoplasmas has been found in commercial vaccines.  In one study 6% of commercial vaccines were found to be contaminated with mycoplasmas [7].  Thus the vaccines used in the Gulf War should be considered as a possible source of the chronic infections found in mycoplasma-positive GWI patients and by airborne transmission in their mycoplasma-positive, CFS-symptomatic family members.  The presence of chronic infections in children who received multiple vaccines and who are now autistic may also be linked in these patients to multiple childhood vaccines, immune suppression and opportunistic infections.  Although complex illnesses like autism are likely to have multiple causes, the presence of chronic infections in many of these children suggest that infections play a role in this illness.

Testing for Chronic Infections Important in Various Illnesses

We suggest that autism patients be tested for the presence of chronic infections, such as Mycoplasma species, Chlamydia pneumoniae, human herpes virus-6 (HHV-6) and other infections. The Institute for Molecular Medicine (www.immed.org) and its certified reference diagnostic laboratory, International Molecular Diagnostics (www.imd-lab.com, tel: 714-799-7177), can test patients for evidence of bacterial and viral infections of the types that are associated with chronic diseases like FMS, CFS, GWI, Rheumatoid Arthritis, autoimmune diseases and autism.  

Prof. Garth L. Nicolson
The Institute for Molecular Medicine (website: www.immed.org)
15162 Triton Lane, Huntington Beach, CA 92649-1401
Tel: 714-903-2900 Fax: 714-379-2082
email: gnicolson@immed.org

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