Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases

Garth L. Nicolson, PhD

Disclosures

Lab Med. 2008;39(5):291-299. 

In This Article

Autism Spectrum Disorders

Autism spectrum disorders (ASD), such as autism, attention deficit disorder, Asperger's syndrome, etc, are neurobehavioral diseases of primarily the young where patients generally suffer from an inability to properly communicate, form relationships with others, and respond appropriately to their environment. Such patients do not all share the same signs and symptoms but tend to share certain social, communication, motor, and sensory problems that affect their behavior in predictable ways. These mostly children often display repetitive actions and develop troublesome fixations with specific objects, and they are often painfully sensitive to certain sounds, tastes, and smells.[3,126,127]

The causes of ASD are unknown but appear to include genetic defects, heavy metal, and chemical and biological exposures, which are probably different in each patient.[3,4,126,127,128] Moreover, in ASD patients, there may be similarities in genetic defects and environmental exposures that are important in patient morbidity or in illness progression.

Chronic infections appear to be an important element in the development of ASD.[14,129] In some patients, there are a number of nonspecific chronic signs and symptoms, such as fatigue, headaches, gastrointestinal and vision problems, and occasional intermittent low-grade fevers and other signs and symptoms that are generally excluded in the diagnosis of ASD.[130] Although nonspecific and not always related to infection, these signs and symptoms suggest that ASD patients could suffer from bacterial or viral infections.[14,130] Indeed, increased titers to various viruses as well as bacterial and fungal infections have been commonly seen in ASD patients,[14,129,130,131] although epidemiological evidence for an association of childhood infections in the first 2 years of life and ASD is lacking.[132] In addition, environmental exposures to chemicals and heavy metals also appear to be important in the development of ASD.[126,127,133]

Although controversial, the relationship between ASD and heavy metals may involve the role of multiple vaccines in ASD pathogenesis.[126,127] ASD patients often show their first signs and symptoms after multiple childhood immunizations.[126] Rimland[126] noted that the sharp rise in Autism rates occurred only after the multiple vaccine MMR came into widespread use, and now in some states in the U.S., children receive as many as 33 vaccines before they can enroll in school. Such vaccines often contain mercury and other preservatives,[127] and some may also contain contaminating bacteria, as found in veterinary vaccines.[134]

Previously we found that 42 veterans of the Gulf War with chronic fatiguing illnesses (Gulf War illness) exhibited multiple nonspecific signs and symptoms similar to chronic fatigue syndrome/ myalgic encephalomyopathy (CFS/MS).[135,136] Interestingly, their symptomatic children (N=35) were often diagnosed with autism or attention deficit disorder, 2 disorders that fall under ASD.[137,138] In our study, approximately 42% of Gulf War illness patients had mycoplasmal infections, and almost all of these (approximately 82%) were single infections, usually M. fermentans. 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. In contrast, in healthy control subjects (N=70), only 8.5% were positive for any mycoplasmal infection and all of these were single infections of various types.[137,138]

When we examined the immediate family members (N=107) of veterans with Gulf War illness, we found that more than 53% had positive tests for mycoplasmal infections and showed symptoms of CFS. Among the CFS-symptomatic family members, most (>70%) had mycoplasmal infections compared with the few nonsymptomatic family members who had similar infections. When the incidence of mycoplasmal infections was compared within families, the CFS-positive family members were more likely to have mycoplasmal infections compared with nonsymptomatic family members (P <0.001).[137] Symptomatic children (mostly ASD, N=35) were also infected with M. fermentans, and this was not seen in aged-matched control subjects. Although some nonsymptomatic family members did have mycoplasmal infections (approximately 10%), this was not significantly different from the incidence of mycoplasmal infections in healthy control subjects (8.5%).[137,138]

Examining ASD patients (N=28) who were not in military families for systemic mycoplasmal infections showed that the majority (approximately 54%) were postive for mycoplasmal infections. However, in contrast to the children of Gulf War illness patients who for the most part had only 1 type of mycoplasmal infection, M. fermentans, the civilian children tested positive for a variety of Mycoplasma species. We also tested a few siblings without apparent signs and symptoms, and for the most part few had these infections.[138] In another study we examined the blood of ASD patients (N=48) from Central and Southern California and found that a large subset (>58%) of patients showed evidence of Mycoplasma infections compared with age-matched control subjects (odds ratio=13.8, P <0.001).[14] ASD patients were also examined for C. pneumoniae (8.3% positive, odds ratio=5.6, P <0.01) and HHV6 (29.2% positive, odds ratio=4.5, P <0.01). The results indicated that a large subset of ASD patients display evidence of bacterial and/or viral infections (odds ratio=16.5, P <0.001).[14]

Recently, ASD patients have been examined for B. burgdorferi infections. Various studies revealed that 22% to 30% of ASD patients (N=76) have Borrelia infections.[139] The incidence of Borrelia infections in ASD patients may be related to Lyme disease (LD) distribution, with some LD-intense areas having high prevalence and other areas having low prevalence.

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