Prescribed stimulant medications: Trends in the last decade, pre and post COVID-19 response.

Background: Recent studies indicate that COVID-19 has had a significant impact on access and continuity to opioid and benzodiazepine medications; little is known about its effect on access to and utilization of stimulant medications. Objective: To investigate trends of dispensed stimulant medications in relation to the COVID-19 pandemic response. Methods: Stimulant prescriptions dispensed during 2011-2021 were analyzed using the Massachusetts Prescription Drug Monitoring Program (PDMP), the state's data repository for all controlled substance medications dispensed to residents from retail pharmacies and out of state mail-order pharmacies. Statewide trends were estimated by age group, sex, and stimulant-naïve patients (individuals with no stimulant prescription in the prior one-year period). Results: Overall, stimulant prescriptions increased 70% from 2011 to 2021. Wide differences by sex and age groups were found pre and post COVID response periods. Between 2019 and 2021, stimulant prescriptions for males 12-18 years old decreased 14.6% compared to 0.9% for females. Female stimulant-naïve patients ages 25-34 increased more than males between 2019 and 2021 (11.6% compared to <1%, respectively) and females ages 35-44 increased 4.1% while males decreased by 2.7%. Conclusions: Administrators, clinicians, and policy makers should closely monitor stimulant prescribing trends, a critical step in improving access to and quality of care.

Where boundaries become bridges: Mosquito community composition, key vectors, and environmental associations at forest edges in the central Brazilian Amazon.

Risk of spillover and spillback of mosquito-borne viruses in the neotropics, including yellow fever, dengue, Zika (Flaviviridae: Flavivirus), chikungunya, and Mayaro (Togaviridae: Alphavirus) viruses, is highest at ecotones where humans, monkeys, and mosquitoes coexist. With a view to identifying potential bridge vectors, we investigated changes in mosquito community composition and environmental variables at ground level at distances of 0, 500, 1000, and 2000 m from the edge of a rainforest reserve bordering the city of Manaus in the central Brazilian Amazon. During two rainy seasons in 2019 and 2020, we sampled 9,467 mosquitoes at 244 unique sites using BG-Sentinel traps, hand-nets, and Prokopack aspirators. Species richness and diversity were generally higher at 0 m and 500 m than at 1000 m and 2000 m, while mosquito community composition changed considerably between the forest edge and 500 m before stabilizing by 1000 m. Shifts in environmental variables mainly occurred between the edge and 500 m, and the occurrence of key taxa (Aedes albopictus, Ae. scapularis, Limatus durhamii, Psorophora amazonica, Haemagogus, and Sabethes) was associated with one or more of these variables. Sites where Ae. aegypti and Ae. albopictus were detected had significantly higher surrounding mean NDBI (Normalized Difference Built-up Index) values than sites where they were not detected, while the opposite was true for Sabethes mosquitoes. Our findings suggest that major changes in mosquito communities and environmental variables occur within 500 m of the forest edge, where there is high risk for contact with both urban and sylvatic vectors. By 1000 m, conditions stabilize, species diversity decreases, and forest mosquitoes predominate. Environmental variables associated with the occurrence of key taxa may be leveraged to characterize suitable habitat and refine risk models for pathogen spillover and spillback.

Detection of Zika Virus in Aedes aegypti and Aedes albopictus Mosquitoes Collected in Urban Forest Fragments in the Brazilian Amazon.

Zika virus (ZIKV) is an RNA flavivirus (Flaviviridae family) endemic in tropical and subtropical regions that is transmitted to humans by Aedes (Stegomyia) species mosquitoes. The two main urban vectors of ZIKV are Aedes aegypti and Aedes albopictus, which can be found throughout Brazil. This study investigated ZIKV infection in mosquito species sampled from urban forest fragments in Manaus (Brazilian Amazon). A total of 905 non-engorged female Ae. aegypti (22 specimens) and Ae. albopictus (883 specimens) were collected using BG-Sentinel traps, entomological hand nets, and Prokopack aspirators during the rainy and dry seasons between 2018 and 2021. All pools were macerated and used to inoculate C6/36 culture cells. Overall, 3/20 (15%) Ae. aegypti and 5/241 (2%) Ae. albopictus pools screened using RT-qPCR were positive for ZIKV. No supernatants from Ae. aegypti were positive for ZIKV (0%), and 15 out of 241 (6.2%) Ae. albopictus pools were positive. In this study, we provide the first-ever evidence of Ae. albopictus naturally infected with ZIKV in the Amazon region.

Towards the Laboratory Maintenance of Haemagogus janthinomys (Dyar, 1921), the Major Neotropical Vector of Sylvatic Yellow Fever.

Haemagogus (Haemagogus) janthinomys (Dyar, 1921), the major neotropical vector of sylvatic yellow fever virus, is notoriously difficult to maintain in captivity. It has never been reared beyond an F1 generation, and almost no experimental transmission studies have been performed with this species since the 1940s. Herein we describe installment hatching, artificial blood feeding, and forced-mating techniques that enabled us to produce small numbers of F3 generation Hg. janthinomys eggs for the first time. A total of 62.8% (1562/2486) F1 generation eggs hatched during ≤10 four-day cycles of immersion in a bamboo leaf infusion followed by partial drying. Hatching decreased to 20.1% (190/944) in the F2 generation for eggs laid by mosquitoes copulated by forced mating. More than 85% (79/92) female F2 mosquitoes fed on an artificial blood feeding system. While we were unable to maintain a laboratory colony of Hg. janthinomys past the F3 generation, our methods provide a foundation for experimental transmission studies with this species in a laboratory setting, a critical capacity in a region with hyper-endemic transmission of dengue, Zika, and chikungunya viruses, all posing a risk of spillback into a sylvatic cycle.

Microclimate and the vertical stratification of potential bridge vectors of mosquito­borne viruses captured by nets and ovitraps in a central Amazonian forest bordering Manaus, Brazil.

In the Americas, some mosquito-borne viruses such as Zika, chikungunya, and dengue circulate among humans in urban transmission cycles, while others, including yellow fever and Mayaro, circulate among monkeys in sylvatic cycles. The intersection of humans and wildlife at forest edges creates risk for zoonotic virus exchange. We built a scaffold tower at the edge of a treefall gap in rainforest bordering Manaus, Brazil, to identify vectors that may bridge transmission between humans and monkeys. We vertically sampled diurnally active, anthropophilic mosquitoes using handheld nets at 0, 5, and 9 m and container-breeding mosquitoes in ovitraps at 0, 5, 10, and 15 m. Haemagogus janthinomys and Psorophora amazonica were present in high relative abundance in nets at each height sampled, while anthropophilic species were uncommon in ovitraps. Hg. janthinomys was more abundant at elevated heights than at ground level, while Ps. amazonica abundance was not significantly stratified across heights. The presence of each species increased with increasing 7-day rainfall lagged at 1 week, and at 1 and 4 weeks prior to collection, respectively. In addition, Hg. janthinomys was most frequently collected at 29.9 °C, irrespective of height. These data provide insight into the potential role of each species as bridge vectors.

Into the woods: Changes in mosquito community composition and presence of key vectors at increasing distances from the urban edge in urban forest parks in Manaus, Brazil.

Mosquito-borne Zika virus (ZIKV) was recently introduced into the Americas and now has the potential to spill back into a sylvatic cycle in the region, likely involving non-human primates and Aedes, Haemagogus, and Sabethes species mosquitoes. We investigated potential routes of mosquito-borne virus exchange between urban and sylvatic transmission cycles by characterizing mosquito communities in three urban forest parks that receive heavy traffic from both humans and monkeys in Manaus, Brazil. Parks were stratified by both distance from the urban-forest edge (0, 50, 100, and 500 m) and relative Normalized Difference Vegetation Index (NDVI) (low, medium, or high), and mosquitoes were sampled at randomly selected sites within each stratum using BG-Sentinel traps. Additionally, temperature, relative humidity, and other environmental data were collected at each site. A total of 1,172 mosquitoes were collected from 184 sites sampled in 2018, of which 98 sites were resampled in 2019. Using park as the unit of replication (i.e. 3 replicates per sampling stratum), a two-way ANOVA showed no effect of distance or NDVI on the mean number of identified species (P > 0.05 for both comparisons) or on species diversity as measured by the Shannon-Wiener diversity index (P > 0.10 for both comparisons). However, the Morisita overlap index revealed that mosquito communities changed substantially with increasing distance from edge, with communities at 0 m and 500 m being quite distinct. Aedes albopictus and Ae. aegypti penetrated at least 100 m into the forest, while forest specialists including Haemagogus janthinomys, Sabethes glaucodaemon, and Sa. tridentatus were detected in low numbers within 100 m from the forest edge. Trichoprosopon digitatum and Psorophora amazonica were among the most abundant species collected, and both showed distributions extending from the forest edge to its interior. Our results show overlapping distributions of urban and forest mosquitoes at park edges, which highlights the risk of arbovirus exchange via multiple bridge vectors in Brazilian urban forest parks. These parks may also provide refugia for both Ae. albopictus and Ae. aegypti from mosquito control programs.

The vertical stratification of potential bridge vectors of mosquito-borne viruses in a central Amazonian forest bordering Manaus, Brazil.

The emergence of Zika virus (ZIKV) in Latin America brought to the fore longstanding concerns that forests bordering urban areas may provide a gateway for arbovirus spillback from humans to wildlife. To bridge urban and sylvatic transmission cycles, mosquitoes must co-occur with both humans and potential wildlife hosts, such as monkeys, in space and time. We deployed BG-Sentinel traps at heights of 0, 5, 10, and 15 m in trees in a rainforest reserve bordering Manaus, Brazil, to characterize the vertical stratification of mosquitoes and their associations with microclimate and to identify potential bridge vectors. Haemagogus janthinomys and Sabethes chloropterus, two known flavivirus vectors, showed significant stratification, occurring most frequently above the ground. Psorophora amazonica, a poorly studied anthropophilic species of unknown vector status, showed no stratification and was the most abundant species at all heights sampled. High temperatures and low humidity are common features of forest edges and microclimate analyses revealed negative associations between minimum relative humidity, which was inversely correlated with maximum temperature, and the occurrence of Haemagogus and Sabethes mosquitoes. In this reserve, human habitations border the forest while tamarin and capuchin monkeys are also common to edge habitats, creating opportunities for the spillback of mosquito-borne viruses.

Adesão à terapia farmacológica em pacientes com hanseníase / Adherence to pharmacological therapy in patients with hansen's disease / Adherencia a la terapia farmacológica en pacientes con lepra

A hanseníase é uma doença infecciosa crônica causada pelo Mycobacterium leprae, considerada um grave problema de saúde pública. A adesão à terapia farmacológica contribui para a qualidade de vida do paciente e para a interrupção da cadeia de transmissão da doença. Este trabalho objetivou analisar a adesão à poliquimioterapia em pacientes com hanseníase acompanhados em um serviço de atendimento especializado do município de Rondonópolis (MT). Trata-se de um estudo descritivo de abordagem quantitativa. Participaram da pesquisa 63 pacientes com diagnóstico de hanseníase, acompanhados no Serviço de Atendimento Especializado do Município de Rondonópolis. Para analisar a adesão, utilizou-se o teste de Morisky-Green. Foram classificados como aderentes ao tratamento 31 pacientes (49,2%) no total. As menores frequências de adesão foram observadas em mulheres, na faixa etária de 51 a 59 anos, de cor autodeclarada branca, renda familiar superior ou igual a dois salários mínimos, com até oito anos de estudo, sem companheiros e que possuíam rede de esgoto em suas residências. Observou-se diferença estatística para as variáveis sexo (p = 0,036), modo de detecção (p = 0,008) e forma clínica (p = 0,028). Os resultados indicaram baixa adesão à poliquimioterapia. Mulheres, pacientes com modo de detecção do tipo encaminhamento ou exames de coletividade, com forma clínica indeterminada, tuberculoide ou virchowiana são menos aderentes à poliquimioterapia. Os resultados indicam a necessidade de adoção de medidas que busquem promover melhor aceitação à terapia farmacológica entre os pacientes com hanseníase.

Hansen's disease, a chronic infectious disease caused by Mycobacterium leprae, is considered a major public health issue. Adherence to pharmacological therapy contributes to the patient's quality of life and to interrupting the disease transmission chain. Hence, this study analyzes adherence to multidrug therapy in patients with Hansen's disease treated at a specialized care service in Rondonópolis, Mato Grosso, Brazil. A quantitative, descriptive research was carried out with 63 patients diagnosed with Hansen's disease and treated at the Specialized Care Service of the municipality of Rondonópolis. Adherence was analyzed using the Morisky-Green test. A total of 31 (49.2%) patients were classified as adherent to treatment. The lowest frequency of adherence was observed in women, aged 51 to 59 years, white, family income ≥ 2 minimum wages, with up to eight years of schooling, without partners, and with a sewage system in their homes. Statistical difference was observed for the variables gender (p=0.036), detection mode (p=0.008), and clinical form (p=0.028). Results showed low adherence to multidrug therapy. Women, patients with referral detection or collective exams, with undetermined clinical form, tuberculoid or Lepromatous leprosy, are less adherent to polychemotherapy. The findings indicate the need to adopt measures that seek to promote better adherence to pharmacological therapy among patients with Hansen's disease.

La lepra es una enfermedad infecciosa crónica causada por Mycobacterium leprae y considerada un grave problema de salud pública. La adherencia a la terapia farmacológica contribuye a la calidad de vida del paciente y a la interrupción de la cadena de transmisión de la enfermedad. Este estudio tuvo como objetivo analizar la adherencia a la poliquimioterapia en pacientes con lepra seguidos en un servicio de atención especializado en la ciudad de Rondonópolis, en Mato Grosso (Brasil). Se trata de un estudio descriptivo, de tipo cuantitativo. Participaron en la investigación 63 pacientes diagnosticados de lepra, seguidos en el Servicio de Atención Especializado del Municipio de Rondonópolis. Para analizar la adherencia se utilizó la prueba de Morisky-Green. Un total de 31 (49,2%) pacientes fueron clasificados como adherentes al tratamiento. La menor frecuencia de adherencia se observó en mujeres, en el grupo de edad de entre 51 y 59 años, de color autodeclarado blanco, renta familiar mayor o igual a 2 salarios mínimos, con nivel de educación hasta ocho años, sin pareja y que tenían red de alcantarillado en sus hogares. Hubo diferencia estadística para la variable sexo (p = 0,036), modo de detección (p = 0,008) y forma clínica (p = 0,028). Los resultados indicaron una baja adherencia a la poliquimioterapia. Las mujeres, los pacientes con modo de detección por derivación o exámenes colectivos, con forma clínica indeterminada, tuberculoide o virchowiana fueron los menos adherentes a la poliquimioterapia. Los resultados indican la necesidad de adoptar medidas que busquen promover una mejor aceptación de la terapia farmacológica entre los pacientes con lepra.

Estudo de insetos vetores de Mansonella spp. no município de São Gabriel da Cachoeira, Amazonas, Brasil

A mansonelose é uma doença parasitária transmitida por vetores filariais considerada autóctone no continente americano. Tem ampla distribuição na região amazônica, afetando populações ribeirinhas dos rios Negro e Solimões, onde ocorre principalmente em vilas e povoados da zona rural e silvestre, onde predominam as populações indígenas. Por ser uma doença negligenciada, há necessidade de se conhecer mais sobre sua transmissão e epidemiologia em áreas endêmicas como o Município de São Gabriel da Cachoeira ­ Amazonas, Brasil. Um passo importante para entender a epidemiologia da Mansonelose é conhecer mais sobre os vetores envolvidos na transmissão desses parasitas, cujo conhecimento aprofundado pode ajudar a orientar os programas de vigilância e controle. Dentre os insetos conhecidos como transmissores de Mansonella spp, destaca-se a espécie de simulídeo, Simulium oyapockense. Este é um complexo bem conhecido de espécies crípticas que podem diferir em sua ecologia, comportamento e capacidade de transmitir parasitas, mas são difíceis de diferenciar com base em características morfológicas. Neste projeto, investigamos a ocorrência de variantes genéticas de S. oyapockense antropofílicas (no final de setembro e outubro 2017) presentes em São Gabriel da Cachoeira com base na análise do DNA mitocondrial (gene COI). Com base na identificação morfológica e molecular de S. oyapockense, avaliamos variações no gene mitocondrial citocromo c oxidase (COI) de 99 espécimes. A análise das sequências de consenso revelou a presença de seis SNPs e três grupos de variantes genéticas, mas não Simulium ´S´, que foi recentemente coletado na área. Nossos resultados mostram a presença de variantes genéticas dentro do complexo S. oyapockense em São Gabriel da Cachoeira, porém mais estudos são necessários para entender seu significado epidemiológico. O fato de não ter sido encontrado a forma Simulium 'S' provavelmente indica que não é uma espécie antropofílico ou estava ausente durante o período de estudo.