INFECTIOUS AGENTS, ASSOCIATED WITH AUTISM, CAUSE IMMUNE SYSTEM DYSFUNCTION, BRAIN DAMAGE, AND INFLAMMATION (EXAMPLES)
Congenital herpesviruses
Herpesviridae is a family of double-stranded DNA viruses, of which seven are known to infect humans and may be the cause of neurological diseases: (i) herpes simplex virus 1 (HSV-1), (ii) herpes simplex virus 2 (HSV-2), (iii) varicella zoster virus (VZV), (iv) human cytomegalovirus (CMV), (v) Epstein-Barr virus (EBV), (vi) human herpesvirus 6 (HHV-6), and (vii) human herpesvirus 7 (HHV-7). Following infection, herpesviruses establish latent infection within specific tissues/organs, characteristic for each virus, and can potentially reactivate in the case of immunity suppression[1]
Human herpesviruses (HHVs) have developed numerous mechanisms of immune system suppression, evasion, and immunosenescence[2] [3]. These viruses possess the ability to alter almost every aspect of human immunity, weakening it, leading to many chronic and persistent diseases. Indeed, herpesviruses evolved to utilize their hosts’ immune system to remain latent and initiate replication only under favorable for the virus conditions, which is primarily an immunocompromised state of the host[4]. There is mounting evidence that infectious agents and inflammation can play a role in neurodegenerative and neurodevelopmental disorders. For example, HSV has the capacity to induce neuroinflammation by establishing persistent encephalitis, myelitis, and meningitis and produce damage to frontal or temporal lobes of the brain[5] [6] [7] [8]. It causes neurological impairments by infecting sensory neurons of the epithelial mucosa and travels in a retrograde manner to the neuron cell body in the peripheral and central nervous system where it establishes persistent infection and remains in a latent state until reactivated by different stimuli[9]. HSV has been related to bipolar illness, schizophrenia, cognitive impairment, lowered executive functions[10] and can produce newborn encephalitis, which resembles autism's early symptoms[11]. Congenital varicella syndrome, caused by VZV, develops when a mother is infected with the virus between 13 and 28 weeks of gestation[12] [13]. Neonatal VZV infection, a devastating disorder involved in developing aseptic meningitis, encephalitis, vasculitis, myelitis, and cranial neuropathy[14] [15]. When it comes to congenital CMV, the consequences of this infection can be detrimental to a fetus. The viral infection may lead to sensorineural loss and a wide range of other neurologic problems in newborns exposed to CMV in utero[16] 35. Congenital CMV can cause malformations of the brain, demyelinating disorders, cerebral atrophy, calcified leukoencephalopathies, leading to developmental delay, seizures, anemia, and sensorineural hearing loss[17].
Congenital Rubella
Rubella virus (RV) is a single-stranded plus-sense RNA virus that is transmitted via aerosol droplets, causing lymphadenopathy, cough, and flu-like symptoms in the infected patients[18]. RV may cause congenital rubella syndrome (CRS) with common presenting signs of blindness, hepatosplenomegaly, sensorineural hearing impairment, congenital heart disease, jaundice, overactivation of innate immunity, encephalitis and various brain defects[19] [20] [21] [22]. RV infection early in utero can cause a profound effect on the developing immune system, such as complete immune paralysis, PHA unresponsiveness, and immunoglobulin abnormalities[23].
Congenital Chlamydia
Neonatal chlamydial infection is a significant cause of neonatal morbidity[24]. Chlamydial pneumonia, caused by the bacteria Chlamydia pneumoniae, is a respiratory illness that can affect humans. It can be transmitted from a pregnant woman to her infant during vaginal delivery, or by aspiration of infected genital secretions during delivery. Chlamydia pneumoniae is a powerful inflammatory trigger and leads to an immunoglobulin E reactivity and a wide spectrum of other human diseases[25].
Mycoplasma pneumoniae
Mycoplasma pneumoniae is a bacterium that can infect children who have autism. The bacterium is responsible for causing an acute variant of pneumonia that is not normal, as well as chronic forms of inflammatory disorders. Infection resulting from this bacterium might present with decreased awareness, seizures, paralysis of cranial nerves, one side body paresis (hemiparesis), Guillain-Barré syndrome, and other forms of neuropsychiatric conditions. The potential methods by which mycoplasma exerts its harmful effect include inducing genomic instability and disrupting the regulation of many genes. This can lead to the development of structural and functional abnormalities in multiple organs and systems of the body. Mycoplasma pneumoniae infection is linked to several symptoms in the central nervous system (CNS), including encephalitis, aseptic meningitis, acute transverse myelitis, stroke, and polyradiculopathy[26] [27].
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