Fatal Case of Naegleria fowleri Primary Amebic Meningoencephalitis from Indoor Surfing Center, Taiwan, 2023.

We investigated a fatal case of primary amoebic meningoencephalitis from an indoor surfing center in Taiwan. The case was detected through encephalitis syndromic surveillance. Of 56 environmental specimens, 1 was positive for Naegleria fowleri ameba. This report emphasizes the risk for N. fowleri infection from inadequately disinfected recreational waters, even indoors.

Benefits of Neuronal Preferential Systemic Gene Therapy for Neurotransmitter Deficiency.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disease that impairs synthesis of dopamine and serotonin. Children with AADC deficiency exhibit severe motor, behavioral, and autonomic dysfunctions. We previously generated an IVS6+4A>T knock-in mouse model of AADC deficiency (Ddc(KI) mice) and showed that gene therapy at the neonatal stage can rescue this phenotype. In the present study, we extended this treatment to systemic therapy on young mice. After intraperitoneal injection of AADC viral vectors into 7-day-old Ddc(KI) mice, the treated mice exhibited improvements in weight gain, survival, motor function, autonomic function, and behavior. The yfAAV9/3-Syn-I-mAADC-treated mice showed greater neuronal transduction and higher brain dopamine levels than AAV9-CMV-hAADC-treated mice, whereas AAV9-CMV-hAADC-treated mice exhibited hyperactivity. Therefore, neurotransmitter-deficient animals can be rescued at a young age using systemic gene therapy, although a vector for preferential neuronal expression may be necessary to avoid hyperactivity caused by this treatment.

Regulation of the dopaminergic system in a murine model of aromatic L-amino acid decarboxylase deficiency.

Aromatic l-amino acid decarboxylase (AADC) is responsible for the syntheses of dopamine and serotonin. Children with AADC deficiency exhibit compromised development, particularly with regard to their motor functions. Currently, no animal model of AADC deficiency exists. We inserted an AADC gene mutation (IVS6+4A>T) and a neomycin-resistance gene into intron 6 of the mouse AADC (Ddc) gene. In the brains of homozygous knock-in (KI) mice (Ddc(IVS6/IVS6)), AADC mRNA lacked exon 6, and AADC activity was <0.3% of that in wild-type mice. Half of the KI mice were born alive but grew poorly and exhibited severe dyskinesia and hindlimb clasping after birth. Two-thirds of the live-born KI mice survived the weaning period, with subsequent improvements in their growth and motor functions; however, these mice still displayed cardiovascular dysfunction and behavioral problems due to serotonin deficiencies. The brain dopamine levels in the KI mice increased from 9.39% of the levels in wild-type mice at 2weeks of age to 37.86% of the levels in wild-type mice at 8weeks of age. Adult KI mice also exhibited an exaggerated response to apomorphine and an elevation of striatal c-Fos expression, suggesting post-synaptic adaptations. Therefore, we generated an AADC deficient mouse model, in which compensatory regulation allowed the mice to survive to adulthood. This mouse model will be useful both for developing gene therapies for AADC deficiency and for designing treatments for diseases associated with neurotransmitter deficiency.