The Association Between Herpes Simplex Viruses and Autism

The Association Between Herpes Simplex Viruses (Type One and Two) and Autism Spectrum Disorders

Autism spectrum disorders are pervasive developmental disorders that include autistic disorder, Asperger's disorder, and pervasive developmental disorder-not otherwise specified.They are characterized by stereotypic behaviors, variable deficits in language and social skills and a wide range of other behavioral problems. Autism spectrum disorders manifest during childhood and at least thirty percent present with sudden clinical regression of development around three years of age.

Study Overview

• Status: Unknown
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Genetic: enzyme linked immunosorbent assay and polymerase chain reaction

Detailed Description

Over the last twenty years, there has been an impressive rise in Autism spectrum disorders with current prevalence estimates being about one over one hundred children.

Herpes simplex virus encephalitis is the leading cause of sporadic, nonepidemic encephalitis in children and adults in the United States. It is an acute necrotizing infection generally involving the frontal and/or temporal cortex and the limbic system and, beyond the neonatal period, is almost always caused by Herpes simplex virus type on.

The etiology of autism is unknown; data suggest that autism results from multiple etiologies with both genetic and environmental contributions. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system, through infection elsewhere in the body acting as a trigger for disease in the central nervous system, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known.

Many encephalitic patients had temporal lobe involvement. Autism results from neuropathology relating to the temporal lobes. They speculate the differences in the extent and neuropathologies of the temporal lobes contribute to the heterogeneity of autism. Also, herpes viruses can induce a variety of proinflammatory cytokines during infections, along with elevated interferon in the brain during Herpes simplex virus encephalitis.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children suffering from Autism Spectrum disorders of variable grades attending to Assuit University Children Hospital and the same number of healthy children of matching age and sex as a control.

Age between six months and five years

Description

Inclusion Criteria:

1. Children suffering from Autism spectrum disorders.
2. Age between six months and five years

Exclusion Criteria:

1. Genetic disorders.
2. History of metabolic or neurodegenerative disease.
3. Gross motor delay.
4. Audiologic problems.
5. Mental retardation.
6. Other psychiatric problems.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
case group; Children suffering from Autism Spectrum disorders of variable grades attending to assiut University Children Hospital aged between six months and five years.	Genetic: enzyme linked immunosorbent assay and polymerase chain reaction; Blood samples will be collected and analyzed for herpes simplex viruses (type one and two) antibody by sensitive enzyme-linked immunosorbent assay and quantitative polymerase chain reaction.
control group; Healthy children of matching age and sex.	Genetic: enzyme linked immunosorbent assay and polymerase chain reaction; Blood samples will be collected and analyzed for herpes simplex viruses (type one and two) antibody by sensitive enzyme-linked immunosorbent assay and quantitative polymerase chain reaction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relationship between herpes simplex viruses infections and development of autism.	Detection of herpes simplex viruses antibody titre by sensitive enzyme linked immunosorbent assay and detection of herpes simplex viruses titre by quantitative polymerase chain reaction	12 month

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Johnson CP, Myers SM; American Academy of Pediatrics Council on Children With Disabilities. Identification and evaluation of children with autism spectrum disorders. Pediatrics. 2007 Nov;120(5):1183-215. doi: 10.1542/peds.2007-2361. Epub 2007 Oct 29.
• Zappella M. Autistic regression with and without EEG abnormalities followed by favourable outcome. Brain Dev. 2010 Oct;32(9):739-45. doi: 10.1016/j.braindev.2010.05.004. Epub 2010 Aug 12.
• Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009 Jun;65(6):591-8. doi: 10.1203/PDR.0b013e31819e7203.
• Libbey JE, Sweeten TL, McMahon WM, Fujinami RS. Autistic disorder and viral infections. J Neurovirol. 2005 Feb;11(1):1-10. doi: 10.1080/13550280590900553.
• DeLong GR, Bean SC, Brown FR 3rd. Acquired reversible autistic syndrome in acute encephalopathic illness in children. Arch Neurol. 1981 Mar;38(3):191-4. doi: 10.1001/archneur.1981.00510030085013.
• Gillberg C. Onset at age 14 of a typical autistic syndrome. A case report of a girl with herpes simplex encephalitis. J Autism Dev Disord. 1986 Sep;16(3):369-75. doi: 10.1007/BF01531665. No abstract available.
• Ghaziuddin M, Tsai LY, Eilers L, Ghaziuddin N. Brief report: autism and herpes simplex encephalitis. J Autism Dev Disord. 1992 Mar;22(1):107-13. doi: 10.1007/BF01046406. No abstract available.
• Hetzler BE, Griffin JL. Infantile autism and the temporal lobe of the brain. J Autism Dev Disord. 1981 Sep;11(3):317-30. doi: 10.1007/BF01531514.
• Dalod M, Salazar-Mather TP, Malmgaard L, Lewis C, Asselin-Paturel C, Briere F, Trinchieri G, Biron CA. Interferon alpha/beta and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. J Exp Med. 2002 Feb 18;195(4):517-28. doi: 10.1084/jem.20011672.
• Salazar-Mather TP, Hamilton TA, Biron CA. A chemokine-to-cytokine-to-chemokine cascade critical in antiviral defense. J Clin Invest. 2000 Apr;105(7):985-93. doi: 10.1172/JCI9232.
• Legaspi RC, Gatmaitan B, Bailey EJ, Lerner AM. Interferon in biopsy and autopsy specimens of brain. Its presence in herpes simplex virus encephalitis. Arch Neurol. 1980 Feb;37(2):76-9. doi: 10.1001/archneur.1980.00500510034004.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2017
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): February 1, 2019

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): June 8, 2017
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Skin Diseases; Virus Diseases; Infections; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Neurodevelopmental Disorders; Herpesviridae Infections; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Herpes Simplex
• Other Study ID Numbers: HA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No