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Background. Pyrethroid insecticides are widely used in many countries for chemical-based control of Ae. aegypti. Regardless of their efficacy, the constant use of insecticides has induced insecticide resistance mechanisms, such as knockdown resistance (kdr) in mosquitoes. Sri Lankan Vector Controlling Entities (VCE) have been using a variety of pyrethroid insecticides as the primary approach for dengue control. However, development of any resistance among the Aedes mosquitoes has been limitedly studied in the country. Therefore, the current study was conducted to evaluate the prevalence of F1534C, V1016G, and S989P mutations among Ae. aegypti mosquito populations in three dengue endemic high-risk regions of Sri Lanka. Methodology. Immature (both pupae and larvae) stages of Ae. aegypti mosquitoes were collected from Colombo, Gampaha, and Kandy districts of Sri Lanka from February 2018 to December 2019. Polymerase Chain Reaction- (PCR-) based assay for molecular genotyping of mutations was performed to identify the prevalence of kdr mutations in collected Ae. aegypti populations, separately. The frequencies of the resistant and susceptible kdr alleles were determined by using the Hardy–Weinberg equilibrium. Results. The Ae. aegypti populations from Colombo, Gampaha, and Kandy districts showed 46%, 42%, and 22% of F1534C mutation allele frequencies, along with 15%, 12%, and 6% of V1016G mutation allele frequencies, respectively. The mutation allele frequencies of S989 in Colombo, Gampaha, and Kandy districts were 9.5%, 8.5%, and 4.5%, respectively. The wild-type (PP) genotype remained predominant within all the three districts, whereas the homogenous (QQ) mutation genotype occurred only in minority. The abundance of Q allele frequency in Ae. aegypti mosquitoes was relatively higher for all the three mutations in Colombo. Conclusions. The findings clearly indicate that long-term insecticide applications and multiple use of pyrethroids have led to the acquisition of kdr mutations, leading to the development of insecticide resistance among local Ae. aegypti populations, especially in the Colombo and Gampaha districts. Therefore, evaluation of the prevalence levels of these kdr mutations highlights the necessity for shifting towards novel vector control strategies.

Background: Epidemiological data on critically ill patients is crucial for understanding resource utilisation, gaps in quality of care and for supporting surveillance of endemic or emerging diseases. We report the epidemiology of critically ill patients from 17 intensive care units (ICUs) in Nepal using an established and standardised ICU registry. Methods: The ICU registry data is collected prospectively and includes data on case mix, severity, organ support and outcomes. We conducted a retrospective observational study with all adult (≥18 years) critically ill patients admitted to 17 ICUs in Nepal between September 2019 and September 2022. We report on case mix, treatment received, severity of illness, standardised mortality rates (SMR), discharge outcomes and ICU service activity. Descriptive statistics were used to report the findings. Results: Of the 18603 unique admissions, 14% were operative, with 35% emergency surgeries. Patients’ median age was 57 (IQR 40-71) and 59% were male. Hypertension and diabetes were common comorbidities and pneumonia accounted for 26% of all admissions. During the ICU stay, 39% of patients received mechanical ventilation, 29% received vasoactive medication and 10% received renal replacement therapy. The median predicted risk of death was 0.1 (IQR 0.1-0.3) using APACHE II and 0.2 (IQR 0.1-0.4) using eTropICS. The median SMR was 0.7 (IQR 0.5-0.8) and 0.8 (IQR 0.6-1.4) using eTropICS and APACHE II, respectively. Median length of stay was 4 days (IQR 2-7). Eighteen percent died in the ICU; of those alive at discharge, 12% went home, 84% went to another department and 3% went to another hospital. COVID-19 was the most common notifiable disease reported (12% of all admissions). Median ICU turnover was 9% (IQR 6-14) with bed capacity ranging from 43-278. Conclusions: These findings should guide forecasting and service planning to ensure ICUs can optimally care for critically ill patients in Nepal.

Background Pyrethroid insecticides are widely used in many countries for chemical-based control of Ae. aegypti. Regardless of their efficacy, the constant use of insecticides has induced insecticide resistance mechanisms, such as knockdown resistance (kdr) in mosquitoes. Sri Lankan Vector Controlling Entities (VCE) have been using a variety of pyrethroid insecticides as the primary approach for dengue control. However, development of any resistance among the Aedes mosquitoes has been limitedly studied in the country. Therefore, the current study was conducted to evaluate the prevalence of F1534C, V1016G, and S989P mutations among Ae. aegypti mosquito populations in three dengue endemic high-risk regions of Sri Lanka. Methodology. Immature (both pupae and larvae) stages of Ae. aegypti mosquitoes were collected from Colombo, Gampaha, and Kandy districts of Sri Lanka from February 2018 to December 2019. Polymerase Chain Reaction- (PCR-) based assay for molecular genotyping of mutations was performed to identify the prevalence of kdr mutations in collected Ae. aegypti populations, separately. The frequencies of the resistant and susceptible kdr alleles were determined by using the Hardy–Weinberg equilibrium. Results The Ae. aegypti populations from Colombo, Gampaha, and Kandy districts showed 46%, 42%, and 22% of F1534C mutation allele frequencies, along with 15%, 12%, and 6% of V1016G mutation allele frequencies, respectively. The mutation allele frequencies of S989 in Colombo, Gampaha, and Kandy districts were 9.5%, 8.5%, and 4.5%, respectively. The wild-type (PP) genotype remained predominant within all the three districts, whereas the homogenous (QQ) mutation genotype occurred only in minority. The abundance of Q allele frequency in Ae. aegypti mosquitoes was relatively higher for all the three mutations in Colombo. Conclusions The findings clearly indicate that long-term insecticide applications and multiple use of pyrethroids have led to the acquisition of kdr mutations, leading to the development of insecticide resistance among local Ae. aegypti populations, especially in the Colombo and Gampaha districts. Therefore, evaluation of the prevalence levels of these kdr mutations highlights the necessity for shifting towards novel vector control strategies.