First national-scale evaluation of temephos resistance in Aedes aegypti in Peru.

BACKGROUND: The development of resistance against insecticides in Aedes aegypti can lead to operational failures in control programs. Knowledge of the spatial and temporal trends of this resistance is needed to drive effective monitoring campaigns, which in turn provide data on which vector control decision-making should be based. METHODS: Third-stage larvae (L3) from the F1 and F2 generations of 39 Peruvian field populations of Ae. aegypti mosquitoes from established laboratory colonies were evaluated for resistance against the organophosphate insecticide temephos. The 39 populations were originally established from eggs collected in the field with ovitraps in eight departments of Peru during 2018 and 2019. Dose-response bioassays, at 11 concentrations of the insecticide, were performed following WHO recommendations. RESULTS: Of the 39 field populations of Ae. aegypti tested for resistance to temephos , 11 showed high levels of resistance (resistance ratio [RR] > 10), 16 showed moderate levels of resistance (defined as RR values between 5 and 10) and only 12 were susceptible (RR < 5). The results segregated the study populations into two geographic groups. Most of the populations in the first geographic group, the coastal region, were resistant to temephos, with three populations (AG, CR and LO) showing RR values > 20 (AG 21.5, CR 23.1, LO 39.4). The populations in the second geographic group, the Amazon jungle and the high jungle, showed moderate levels of resistance, with values ranging between 5.1 (JN) and 7.1 (PU). The exception in this geographic group was the population from PM, which showed a RR value of 28.8 to this insecticide. CONCLUSIONS: The results of this study demonstrate that Ae. aegypti populations in Peru present different resistance intensities to temephos, 3 years after temephos use was discontinued. Resistance to this larvicide should continue to be monitored because it is possible that resistance to temephos could decrease in the absence of routine selection pressures.

Susceptibility to insecticides and resistance mechanisms in three populations of Aedes aegypti from Peru.

BACKGROUND: Epidemics of dengue, chikungunya and Zika are a growing threat to areas where Aedes aegypti are present. The efficacy of chemical control of Ae. aegypti is threatened by the increasing frequency of insecticide resistance. The objective of this study was to determine the susceptibility status as well as the biochemical and molecular mechanisms underlying insecticide resistance in three populations of Ae. aegypti in high risk areas of dengue, chikungunya, and Zika in Peru. METHODS: Bioassays were conducted on adult Ae. aegypti to evaluate their susceptibility to insecticides used currently or historically for mosquito control in Peru, including six pyrethroids, three organophosphates and one organochlorine, in populations of Ae. aegypti from the districts of Chosica (Department of Lima), Punchana (Department of Loreto) and Piura (Department of Piura). Resistance mechanisms were determined by biochemical assays to assess activity levels of key detoxification enzyme groups (nonspecific esterases, multi-function oxidases, glutathione S-transferases and insensitive acetylcholinesterase). Real-time PCR assays were used to detect two kdr mutations (V1016I and F1534C) on the voltage-gated sodium channel gene. RESULTS: Resistance to DDT was detected in all three populations, and resistance to pyrethroids was detected in all populations except the population from Chosica, which still exhibited susceptibility to deltamethrin. Resistance to organophosphates was also detected, with the exception of populations from Punchana and Piura, which still demonstrated susceptibility to malathion. In general, no increase or alteration of activity of any enzyme group was detected. Both 1016I and 1534C alleles were detected in Punchana and Piura, while only the 1534C allele was detected in Chosica. CONCLUSIONS: The results suggest that resistance to multiple classes of insecticides exist in areas important to Ae. aegypti-borne disease transmission in Peru. The F1534C mutation was present in all 3 populations and the V1016I mutation was present in 2 populations. To our knowledge, this is the first report of the presence of 1016I and 1534C in Ae. aegypti in Peru. The absence of highly elevated enzymatic activity suggests that target site resistance is a key mechanism underlying insecticide resistance in these populations, although further research is needed to fully understand the role of metabolic resistance mechanisms in these populations.

Prevalencia y factores asociados con la filariosis por Mansonella ozzardi en 2 comunidades periurbanas de Iquitos, 2009 / Prevalence of filariasis by Mansonella ozzardi and associated factors among 2 suburban communities of Iquitos, 2009

Introducción: Tres casos de infección por Mansonella ozzardi (M. ozzardi) en muestras de malaria que provenían de 2 comunidades periurbanas de Iquitos (Perú) dieron la sospecha de transmisión local. El objetivo del estudio fue determinar la prevalencia y factores asociados con la filariosis por M. ozzardi en estas comunidades. Materiales y métodos: Se realizó un estudio transversal en las comunidades de Laguna Azul y La Unión en Iquitos. A todos los pobladores se les tomó una gota gruesa para la detección de M. ozzardi y se les realizó una encuesta epidemiológica. Se realizó colecta de larvas y mosquitos para identificación de potenciales vectores. Se calcularon los OR ajustados (ORa) usando regresión logística múltiple. Resultados: Se evaluaron a 433 personas; 58% fueron mujeres; la mediana de edad fue de 20 años; 58,2% fueron migrantes, 3,7% pescadores y 12,9% habían viajado por las cuencas del Alto anay. La prevalencia de M. ozzardi fue de 1,4% (6/433) y el más joven de los casos tuvo 31 años; se encontró asociación con ser pescador (ORa: 8,7; IC 95: 1,1-76,0) y con haber realizado viajes por la cuenca del Alto Nanay (ORa: 11,2; IC 95: 1,2-112,5). No se evidenció densidad significativa de vectores simúlidos o culicoides. Conclusión: Las comunidades estudiadas tuvieron una baja prevalencia de M. ozzardi y por la edad de los casos y los factores asociados encontrados se sospecha infección foránea a la zona de estudio, en especial en la cuenca del Alto Nanay.

Introduction: Three cases of M. ozzardi infection from 2 suburban communities in Iquitos, Peru, led to a suspicion of local transmission. The objective of the study was to determine the prevalence of filariasis by M. ozzardi and its associated factors among these communities. Materials and methods: A cross-sectional study was performed, as well as an epidemiological survey and a thick smear blood test. Larvae and mosquitoes were collected. The adjusted OR (aOR) using multiple logistic regression was calculated. Results: A total of 433 participants were enrolled; 58% were women. The prevalence of M. ozzardi was 1.4% and the associated factors included being a fisherman (aOR: 8.7; 95%CI: 1.1-76.0) and being on the Alto Nanay river (aOR: 11.2; 95%CI: 1.2-112.5). No significant evidence of simulidos or culicoides was found. Conclusion: The low prevalence of M. ozzardi found suggests a foreign infection, probably derived from the Alto Nanay river.

Insecticide Resistance in Areas Under Investigation by the International Centers of Excellence for Malaria Research: A Challenge for Malaria Control and Elimination.

Scale-up of the main vector control interventions, residual insecticides sprayed on walls or structures and/or impregnated in bed nets, together with prompt diagnosis and effective treatment, have led to a global reduction in malaria transmission. However, resistance in vectors to almost all classes of insecticides, particularly to the synthetic pyrethroids, is posing a challenge to the recent trend of declining malaria. Ten International Centers of Excellence for Malaria Research (ICEMR) located in the most malaria-endemic regions of the world are currently addressing insecticide resistance in the main vector populations, which not only threaten hope for elimination in malaria-endemic countries but also may lead to reversal where notable reductions in malaria have been documented. This communication illustrates the current status of insecticide resistance with a focus on the countries where activities are ongoing for 9 out of the 10 ICEMRs. Most of the primary malaria vectors in the ICEMR countries exhibit insecticide resistance, albeit of varying magnitude, and spanning all mechanisms of resistance. New alternatives to the insecticides currently available are still to be fully developed for deployment. Integrated vector management principles need to be better understood and encouraged, and viable insecticide resistance management strategies need to be developed and implemented.

[Dengue in Peru: a quarter century after its reemergence]. / Dengue en el Perú: a un cuarto de siglo de su reemergencia.

A health problem each time more frequent and dispersed in tropical and subtropical areas of the world, including Peru where it entered in 1990, is dengue. It is produced by the dengue virus with four serotypes and transmitted by Aedes aegypti, a vector that coexists with humans and whose presence is favored by deficient sanitary, social and economic conditions. Manifestations of severe forms of the disease such as shock and bleeding, are related to the frequent co-circulation of the four serotypes and the emergence of new genotypes such as American/Asian serotype 2. The new classification of the disease by WHO as dengue with or without warning signs and severe dengue, is contributing to more timely diagnosis and treatment, enabling reductions in mortality. Of note is the need to highlight the surveillance of acute febrile illness and Aedes indices that contribute to a timely diagnosis and guide vector control measures through sanitary education and environmental management with community and intersectoral participation, in a creative manner according to ecological niches. An alternative for complementary prevention would be vaccination using tetravalent vaccines whose safety and efficacy must be guaranteed before its use in the population under the framework of comprehensive strategies.

Novel mutations on the ace-1 gene of the malaria vector Anopheles albimanus provide evidence for balancing selection in an area of high insecticide resistance in Peru.

BACKGROUND: Resistance to multiple classes of insecticides has been detected in the malaria vector Anopheles albimanus in northwest Peru. Acetylcholinesterase (AChE) insensitivity has previously been associated with resistance to organophosphate (OP) and carbamate (CA) insecticides in arthropods. A single point mutation on the ace-1 gene (G119S) associated with resistance to OPs and CAs has been described previously in four anopheline species, but not in field-collected An. albimanus. The present study aimed to characterize the role of ace-1 in conferring resistance to both OPs and CAs in the An. albimanus population in Tumbes, Peru. METHODS: The frequency and intensity of resistance to OPs and CAs was quantified through bioassays of female An. albimanus collected between 2012 and 2014, and the presence of insensitive AChE was confirmed using biochemical assays. A portion of the ace-1 gene flanking codon 119 was amplified and sequenced from individuals used in the bioassays and biochemical assays, as well as from historical samples collected in 2008. Statistical analyses were conducted to determine: (1) associations between genotype and AChE insensitivity; and, (2) associations between genotype and resistance phenotype. RESULTS: After confirming high levels of resistance to fenitrothion, malathion, and bendiocarb through bioassays, two novel polymorphisms were identified at the first and second loci of codon 119, with all individuals from the 2012-2014 collections being heterozygous at the first base (G/T) and either heterozygous (G/C) or homozygous mutants (C/C) at the second base. Based on sequence data from historical samples, these mutations arose prior to 2008, but became fixed in the population between 2008 and 2012. Homozygotes at the second locus had significantly higher levels of AChE insensitivity than heterozygotes (p <0.05). Individuals phenotypically susceptible to OPs and CAs were more likely to be heterozygous at the second locus (p <0.01). Cloning identified four individuals each containing three distinct genotypes, suggesting that a duplication of the ace-1 gene may have occurred. CONCLUSIONS: The occurrence of heterozygotes at two loci and the presence of three genotypes in four individuals suggest that balancing selection could be maintaining OP and CA resistance in this population, while minimizing associated fitness costs.

Dengue en el Perú: a un cuarto de siglo de su reemergencia / Dengue in Peru: a quarter century after its reemergence

Un problema sanitario cada vez más frecuente y disperso en áreas tropicales y subtropicales del mundo, incluido el Perú donde ingresó en 1990, es el dengue. Es producido por el virus del dengue con cuatro serotipos y transmitido por el Aedes aegypti, vector que convive con los humanos y cuya presencia es favorecida por deficientes condiciones sanitarias, sociales y económicas. Manifestaciones de formas severas de la enfermedad como el choque y sangrado, están relacionadas con la frecuente cocirculación de los cuatro serotipos y la aparición de nuevos genotipos como el americano/asiático del serotipo 2. La nueva clasificación de la enfermedad por la OMS como dengue con o sin signos de alarma y dengue grave, está contribuyendo a un diagnóstico y tratamiento más oportunos, permitiendo reducir la letalidad. Debe destacarse la necesidad de la vigilancia del síndrome febril y los índices aédicos que contribuyan a un diagnóstico oportuno y orienten las medidas de control vectorial mediante educación sanitaria y manejo ambiental con participación comunitaria e intersectorial, de manera creativa según los nichos ecológicos. Una alternativa de prevención complementaria sería la vacunación utilizando vacunas tetravalentes cuya seguridad y eficacia deben estar garantizadas antes de su uso poblacional en el marco de estrategias integrales.

A health problem each time more frequent and dispersed in tropical and subtropical areas of the world, including Peru where it entered in 1990, is dengue. It is produced by the dengue virus with four serotypes and transmitted by Aedes aegypti, a vector that coexists with humans and whose presence is favored by deficient sanitary, social and economic conditions. Manifestations of severe forms of the disease such as shock and bleeding, are related to the frequent co-circulation of the four serotypes and the emergence of new genotypes such as American / Asian serotype 2. The new classification of the disease by WHO as dengue with or without warning signs and severe dengue, is contributing to more timely diagnosis and treatment, enabling reductions in mortality. Of note is the need to highlight the surveillance of acute febrile illness and Aedes indices that contribute to a timely diagnosis and guide vector control measures through sanitary education and environmental management with community and intersectoral participation, in a creative manner according to ecological niches. An alternative for complementary prevention would be vaccination using tetravalent vaccines whose safety and efficacy must be guaranteed before its use in the population under the framework of comprehensive strategies.

Eficacia y residualidad de dos insecticidas piretroides contra Triatoma infestans en tres tipos de viviendas: evaluación de campo en Arequipa, Perú / Efficacy and residual efect of two pyrethroid insecticides against Triatoma infestans in thre types of houses: field evaluation in Arequipa, Peru

Objetivos. Comparar la eficacia residual de dos insecticidas en el control vectorial del Triatoma infestans sobre tres tipos de vivienda en dos localidades de Arequipa, Perú. Material y métodos. Ensayo de campo, se utilizaron formulaciones de polvo mojado de deltametrina y lambdacihalotrina sobre diferentes sustratos (concreto, ladrillo y sillar) a dosis de 25 y 30 mg/m2 respectivamente. Se usó 1445 ninfas V de Triatoma infestans en los bioensayos, donde se expuso por 48 horas a los triatominos en la pared rociada y se los observó durante 14 días para evaluar mortalidad. Se realizó la exposición en cada tipo de superficie por insecticida a 24 horas, 30 y 90 días postratamiento. Resultados. A las 24 h la lambdacihalotrina fue más eficaz que la deltametrina en ladrillo y sillar (p < 0,01). A los 30 días la deltametrina tuvo mejor efecto residual en ladrillo y sillar (p < 0,01) y a los 90 días fue superior que la lambdacihalotrina en concreto (73 vs 35%, p < 0,001), ladrillo (62 vs 23%, p < 0,001) y sillar (63 vs 27%, p < 0,001). La reducción de la mortalidad en deltametrina se hizo evidente al tercer mes, siendo similar a las 24h y en el primer mes (p > 0,05). La lambdacihalotrina redujo su eficaciaen 23% mensual desde la primera evaluación (p < 0,001, r2: 0,95). Conclusiones. La lambdacihalotrina es eficaz en los primeros días postratamiento pero su residualidad es pobre, a diferencia de la deltametrina. Estos resultados deben ser tomados en cuenta para calcular los tiempos de aplicación de cada insecticida en el control vectorial de la enfermedad de Chagas según el tipo de material de construcción.

Objetives. To compare the residual efficacy of two insecticides for the vector control of Triatoma infestans on three type of housing in two localities from Arequipa, Peru. Material and methods. Field assay, were used wet powder formulations of deltamethrin and lambdacyhalothrin on different substrates (concrete, brick and sillar [white local volcanic rock]) at doses of 25 and 30 mg/m2 respectively. 1445 Triatoma infestans V nymphs were used in bioassays, where they were exposed for 48 hours on the sprayed wall and were observed for 14 days to assess mortality. The exhibition was held in each type of surface and insecticide for 24 hours, 30 and 90 days after treatment. Results. At 24 h the lambdacyhalothrin was more effective than deltamethrin in brick and sillar (p < 0.01). For the 30 days deltamethrin had better residual effect in brick and sillar (p < 0.01) and 90 days was higher than the lambdacihalothrin in concrete (73 vs 35%, p < 0.001), brick (62 vs 23%, p < 0.001) and sillar (63 vs 27%, p < 0.001). The reduction in mortality in deltamethrin was evident to the third month, were similar to the 24h and the first month (p > 0.05). Lambdacyhalothrin reduced its effectiveness at 23% per month since the first evaluation (p < 0.001, r2: 0.95). Conclusions. Lambdacyhalothrin is effective in the first days after its residual effect is poor but, unlike deltamethrin. These results should be taken into account to calculate the time of spraying of each pesticide on vector control of Chagas disease by type of construction material.

[Insecticide resistance mechanisms of Aedes aegypti (Diptera: Culicidae) from two Peruvian provinces]. / Resistencia a insecticidas y mecanismos de resistencia en Aedes aegypti (Diptera: Culicidae) de 2 provincias del Perú.

Insecticide resistance of Aedes aegypti larvae and adults from two Peruvian provinces, that is, Trujillo and Tumbes provinces, was conducted. High infestation indexes and extensive use of insecticides based on the Vector Surveillance and Control Strategy of the Ministry of Public Health prevailed in these places. Larval bioassays revealed susceptibility to organophosphorate insecticide called malathion in TRUJILLO strain, it being moderate to fention and fenitrotion and high to chlorpyriphos and temephos;however, TUMBES strain was susceptible to the evaluated organophosphorate compounds, except for fention, with moderate resistance. In the adult state, at the recommended dose, TRUJILLO strain showed resistence to DDT organochlorate insecticide and to pyrethoids called lambdacyalotrine and cyflutrine whereas TUMBES was resistant to DDT and to all assessed pyrethoids. None of them was resistant to chlorpiriphos in adult stage. By using synergists, the results showed that esterases and monooxigenases played an important role in the detected resistence to organophosphorate in Aedes larvae from TRUJILLO province. Biochemical assays yielded that increased activity of esterases was very frequent in TRUJILLO strain as was the case of glutathion transferase(GST) and modified acetylcholinesterase (AchR). On the other hand, the polyacrylamide gel electrophoresis allowed observing the prevalence of amplified activity of esterases A4 in TRUJILLO strain but not in TUMBES strain.

Distribución geográfica y comportamiento estacional de la picadura del Anopheles (Nyssorhynchus) darlingi Root 1926 en localidades de la frontera Perú-Bolivia, Madre de Dios, Perú / Geographical distribution and seasonal bite behavior for Anopheles (Nyssorhynchus) darlingi Root 1926 in Peru-Bolivia borderline Madre de Dios, Peru

Objetivos: Determinar la distribución geográfica y el comportamiento estacional de la picadura de Anopheles darlingi en localidades de San Pedro, La Novia, Shiringayoc y Mavila del departamento de Madre de Dios. Materiales y métodos: En estas 4 localidades, durante el periodo comprendido entre junio de 2001 y abril de 2002, se realizó la inspección de criaderos, colecta de larvas de Anopheles darlingi por el método del cucharon y la colecta de mosquitos adultos por el método cebo humano (intradomicilio y peridomicilio), trampa shannon y refugio animal (extradomicilio). Se construyó un mapa de ubicación geográfica del vector, calculándose los indicadores: criadero positivo y densidad larvaria por cucharonada, índice de picadura hombre noche (IPHN), índice de picadura hombre hora (IPHH), índice por esporozoítico y taza de paridad. Resultados: Demostró la presencia de Anopheles darlingi en las localidades de San pedro, La Novia y Mavila. Las especies inmaduras representaron menos del 12 por ciento de las larvas encontradas en los criaderos permanentes. El IPHN en las tres localidades se incrementó en la estació lluviosa (diciembre-abril). La picadura del Anopheles darlingi tuvo un comportamiento ematofágico unimodal, con picos de IPHH entre las 20.00 y 23.00 horas en San Pedro y la Novia; y entre las 20.00 y 22.00 horas en Mavila. Conclusiones: El Anopheles darlingi presenta mayor densidad poblacional en los meses de estación lluviosa, presentando un comportamiento de picadura unimodal con mayor actividad hematofágica entre las 20.00 y 23.00 horas