METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb.
CONCLUSION/SIGNIFICANCE: The predominant over-expression of cytochrome P450s suggests that synergist-based (PBO) control tools could be utilised to improve control of this major dengue vector across Malaysia.
METHODS: A comprehensive literature search was carried out using PubMed, Web of Science, Scopus, and OVID databases until 31 December 2022 by two independent reviewers. All studies from the year 2013 were extracted, and quality assessments were carried out meticulously prior to their inclusion in the final analysis.
RESULTS: A total of 21 studies were selected for qualitative analyses out of the 461 studies extracted. The cases were distributed globally, and 72.7% of the cases succumbed to mortality. The youngest case was an 11-day-old boy, while the eldest was a 75-year-old. Significant exposure to freshwater either from recreational activities or from a habit of irrigating the nostrils preceded onset. The symptoms at early presentation included fever, headache, and vomiting, while late sequalae showed neurological manifestation. An accurate diagnosis remains a challenge, as the symptoms mimic bacterial meningitis. Confirmatory tests include the direct visualisation of the amoeba or the use of the polymerase chain reaction method.
CONCLUSIONS: N. fowleri infection is rare but leads to PAM. Its occurrence is worldwide with a significant risk of fatality. The suggested probable case definition based on the findings is the acute onset of fever, headache, and vomiting with meningeal symptoms following exposure to freshwater within the previous 14 days. Continuous health promotion and health education activities for the public can help to improve knowledge and awareness prior to engagement in freshwater activities.