Mutations Linked to Insecticide Resistance Not Detected in the Ace-1 or VGSC Genes in Nyssorhynchus darlingi from Multiple Localities in Amazonian Brazil and Peru.

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention for preventing malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) genes are non-synonymous, resulting in a change in amino acid, leading to the non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi, the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014 and 2021. The criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi, and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced, and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC. The lack of genotypic detection of insecticide resistance mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

Natural Infection of Nyssorhynchus darlingi and Nyssorhynchus benarrochi B with Plasmodium during the Dry Season in the Understudied Low-Transmission Setting of Datem del Marañon Province, Amazonian Peru.

The persistence of malaria hotspots in Datem del Marañon Province, Peru, prompted vector control units at the Ministry of Health, Loreto Department, to collaborate with the Amazonian International Center of Excellence for Malaria Research to identify the main vectors in several riverine villages that had annual parasite indices > 15 in 2018-2019. Anophelinae were collected indoors and outdoors for two 12-hour nights/community during the dry season in 2019 using human landing catch. We identified four species: Nyssorhynchus benarrochi B, Nyssorhynchus darlingi, Nyssorhynchus triannulatus, and Anopheles mattogrossensis. The most abundant, Ny. benarrochi B, accounted for 96.3% of the total (7,550/7,844), of which 61.5% were captured outdoors (4,641/7,550). Six mosquitoes, one Ny. benarrochi B and five Ny. darlingi, were infected by Plasmodium falciparum or Plasmodium vivax. Human biting rates ranged from 0.5 to 592.8 bites per person per hour for Ny. benarrochi B and from 0.5 to 32.0 for Ny. darlingi, with entomological inoculation rates as high as 0.50 infective bites per night for Ny. darlingi and 0.25 for Ny. benarrochi B. These data demonstrate the risk of malaria transmission by both species even during the dry season in villages in multiple watersheds in Datem del Marañon province.

Variability of anesthetic depth in total intravenous anesthesia vs balanced anesthesia using entropy indices: a randomized, crossover, controlled clinical trial / Variabilidad de la profundidad anestésica en anestesia total intravenosa vs. anestesia general balanceada usando índices de entropía. Un ensayo clínico aleatorizado, cruzado y controlado

Abstract Introduction: Total intravenous anesthesia (TIVA) and balanced anesthesia (BA) are the most commonly used anesthetic techniques. The differences are the variability of the depth of anesthesia between these techniques that might predict which one is safer for patients and presents a lower risk of intraoperative awakening. Objective: To determine whether a difference exists in the variability of depth of anesthesia obtained by response entropy (RE). Methods: A crossover clinical trial was conducted on 20 healthy patients receiving upper or lower limb ambulatory orthopedic surgery. Patients were randomly assigned to (a) target-controlled infusion of propofol using the Schnider model at a target concentration of 2.5 µg/mL for 15 minutes and a 10-minute washout, followed by sevoflurane administration at 0.8 minimal alveolar concentration (MAC) for the reminder of the surgery, or (b) the reverse sequence. Differences in the variability of the depth of anesthesia using RE were evaluated using paired t-test. Results: The treatment effect showed no significant difference in the average values of RE, during TIVA = 97.23 vs BA 97.04 (P = 0.39). Carry Over (-4.98 vs 4.08) and Period (100.3 vs 94.68) effects were not significantly different. Conclusion: The present study suggests that both anesthetic techniques are equivalent in terms of the stability of the depth of anesthesia. It is important to keep testing the determinants of the efficacy of different populations because the individual behaviors of patients might ultimately tip the scale.

Resumen Introducción: La anestesia total intravenosa (TIVA, por sus siglas en inglés) y la anestesia balanceada (AB) son las técnicas anestésicas más comúnmente utilizadas. La diferencia está en la variabilidad de la profundidad de la anestesia entre estas dos técnicas, lo cual pudiera predecir cuál es más segura para los pacientes y representar un menor riesgo de despertar intraoperatorio. Objetivo: Determinar si existe alguna diferencia en la variabilidad de la profundidad de la anestesia obtenida según los índices de entropía de respuesta (ER). Métodos: Se llevó a cabo un estudio clínico cruzado en 20 pacientes sanos que se sometieron a cirugía ortopédica ambulatoria de miembros superiores o inferiores. Los pacientes se asignaron aleatoriamente así: a) infusión controlada por objetivo (TCI, por sus siglas en inglés) de propofol, utilizando el modelo Schnider a una concentración objetivo de 2,5 µg/mL durante 15 min y un período de lavado de 10 minutos, seguido de la administración de sevoflurano a 0,8 de concentración alveolar mínima (CAM) durante el tiempo restante de la cirugía; o b) la secuencia inversa. Las diferencias en la variabilidad de la profundidad de la anestesia utilizando entropía de respuesta se evaluaron utilizando la prueba t pareada. Resultados: El efecto del tratamiento no mostró ninguna diferencia significativa en los valores promedio de entropía de respuesta (ER) durante TIVA = 97,23 vs. AB 97,04 (P = 0,39). Los efectos de arrastre (-4,98 vs. 4,08) y período (100,3 vs. 94,68) no fueron significativamente diferentes. Conclusiones: El presente estudio sugiere que ambas técnicas anestésicas son equivalentes en términos de estabilidad de la profundidad de la anestesia. Es importante continuar probando los factores determinantes de eficacia en las distintas poblaciones, ya que el comportamiento individual de cada paciente pudiera finalmente inclinar la balanza.