Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos, Peru.

Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = -9.11) and 12.4% (95% CI 4.2%, ∞); z = -2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Cell Death in the Lung: The Apoptosis-Necroptosis Axis.

Regulated cell death is a major mechanism to eliminate damaged, infected, or superfluous cells. Previously, apoptosis was thought to be the only regulated cell death mechanism; however, new modalities of caspase-independent regulated cell death have been identified, including necroptosis, pyroptosis, and autophagic cell death. As an understanding of the cellular mechanisms that mediate regulated cell death continues to grow, there is increasing evidence that these pathways are implicated in the pathogenesis of many pulmonary disorders. This review summarizes our understanding of regulated cell death as it pertains to the pathogenesis of chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and pulmonary arterial hypertension.

Sex differences and altered mitophagy in experimental pulmonary hypertension.

Pulmonary hypertension (PH) is a debilitating condition characterized by increased pulmonary arterial pressures and remodeling of pulmonary arteries, leading to right heart failure. Women have a higher prevalence of PH, whereas men have more severe disease and poorer outcomes. Animal models also show female-predominant disease. Despite the known sex differences in PH, little is known about how pathogenesis differs between the sexes. There is growing evidence of mitochondrial dysfunction, as well as altered mitophagy in PH. We hypothesized that sexual dimorphism contributes to mitochondrial dysfunction and altered mitophagy in PH. Using mouse lung endothelial cells, we exposed both wild-type and Parkin-/- cells to hypoxia and measured the effects on mitochondrial function and mitophagy-associated proteins. Our results show that females have more Parkin expression at baseline as well as increased mitochondrial respiratory capacity when exposed to oxidative stress. Inhibition of Parkin increased metabolic activity but reduced cell proliferation but to different degrees depending on sex, with results differing by sex. Our findings demonstrate sexual dimorphism in mitophagy-associated proteins and in mitochondrial respiration, which may help shed light on how the pathogenesis of PH may differ between the sexes.

Embracing the Diversity of Latinx Communities to Promote Vaccinations.

While vaccine hesitancy is well documented in the literature among the Latinx community, little attention or effort is given to the nuances among the members of individual communities, such as country of origin, immigration status, generational status, primary language, race, age, sex, gender, or rural residence and how these complexities affect vaccine messaging and uptake. We have evidence that this heterogeneity causes differences in access to healthcare, attitudes towards vaccines, and degree of health disparities. In this review we will describe their impact on vaccination rates in the Latinx community, highlighting missed opportunities for public health outreach, and how targeted messaging could improve vaccine uptake.

COVID-19 Healthcare Inequity: Lessons Learned from Annual Influenza Vaccination Rates to Mitigate COVID-19 Vaccine Disparities.

The COVID-19 pandemic has infected 33 million Americans and resulted in more than 600,000 deaths as of late Spring 2021. Black, Indigenous, and Latinx (BIL) people are disproportionately infected, hospitalized, and dying. Effective vaccines were rapidly developed and have been widely available in the United States since their initial rollout in late 2020-early 2021 but vaccination rates in BIL communities have remained low compared with non-BIL communities. Limited access to the vaccine, lack of customized information, and mistrust of the medical system, all contribute to vaccine hesitancy and low vaccination rates. Regrettably, COVID-19 is not the only vaccine-preventable illness with racial/ethnic inequities. Similar inequities are seen with the seasonal influenza vaccine. We review the racial/ethnic health disparities in COVID-19 illness and vaccination rates and what inequities contribute to these disparities. We use evidence from the seasonal influenza vaccination efforts to inform potential strategies to attenuate these inequities. The development of effective and sustainable strategies to improve vaccination rates and reduce factors that result in health inequities is essential in managing current and future pandemics and promoting improved health for all communities.

Heterogeneity of Dengue Illness in Community-Based Prospective Study, Iquitos, Peru.

Measuring heterogeneity of dengue illness is necessary to define suitable endpoints in dengue vaccine and therapeutic trials and will help clarify behavioral responses to illness. To quantify heterogeneity in dengue illness, including milder cases, we developed the Dengue Illness Perceptions Response (IPR) survey, which captured detailed symptom data, including intensity, duration, and character, and change in routine activities caused by illness. During 2016-2019, we collected IPR data daily during the acute phase of illness for 79 persons with a positive reverse transcription PCR result for dengue virus RNA. Most participants had mild ambulatory disease. However, we measured substantial heterogeneity in illness experience, symptom duration, and maximum reported intensity of individual symptoms. Symptom intensity was a more valuable predicter of major activity change during dengue illness than symptom presence or absence alone. These data suggest that the IPR measures clinically useful heterogeneity in dengue illness experience and its relation to altered human behavior.

Pulmonary artery pseudoaneurysm causing massive hemoptysis in hyperimmunoglobulin E syndrome: a case report.

BACKGROUND: Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder defined by high serum immunoglobulin E titers that is associated with recurrent respiratory infections, formation of pneumoatoceles, recurrent skin abscesses, and characteristic dental and skeletal abnormalities. CASE PRESENTATION: We report a case of a 56-year-old male with a history of HIES, cavitary mycetomas, and allergic bronchopulmonary aspergillosis who presented with recurrent massive hemoptysis. Bronchial artery angiography and bronchoscopy failed to identify active hemorrhage, and two embolizations of the bronchial artery did not resolve the bleeding. Subsequently, selective pulmonary artery angiography was conducted that demonstrated a subsegmental pulmonary artery branch pseudoaneurysm with extravasation into an adjacent lung cavity. This was treated successfully with transcatheter embolization. CONCLUSIONS: To our knowledge, this is the first case reported of pulmonary artery pseudoaneurysm in HIES in the medical literature. Pulmonary artery pseudoaneurysm should be considered in the differential diagnosis in patients with HIES and massive hemoptysis.

Mitochondrial dysfunction and pulmonary hypertension: cause, effect, or both.

Pulmonary hypertension describes a heterogeneous disease defined by increased pulmonary artery pressures, and progressive increase in pulmonary vascular resistance due to pathologic remodeling of the pulmonary vasculature involving pulmonary endothelial cells, pericytes, and smooth muscle cells. This process occurs under various conditions, and although these populations vary, the clinical manifestations are the same: progressive dyspnea, increases in right ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and right-sided heart failure with systemic circulatory collapse. The overall estimated 5-yr survival rate is 72% in highly functioning patients, and as low as 28% for those presenting with advanced symptoms. Metabolic theories have been suggested as underlying the pathogenesis of pulmonary hypertension with growing evidence of the role of mitochondrial dysfunction involving the major proteins of the electron transport chain, redox-related enzymes, regulators of the proton gradient and calcium homeostasis, regulators of apoptosis, and mitophagy. There remain more studies needed to characterize mitochondrial dysfunction leading to impaired vascular relaxation, increase proliferation, and failure of regulatory mechanisms. The effects on endothelial cells and resulting interactions with their microenvironment remain uncharted territory for future discovery. Additionally, on the basis of observations that the "plexigenic lesions" of pulmonary hypertension resemble the unregulated proliferation of tumor cells, similarities between cancer pathobiology and pulmonary hypertension have been drawn, suggesting interactions between mitochondria and angiogenesis. Recently, mitochondria targeting has become feasible, which may yield new therapeutic strategies. We present a state-of-the-art review of the role of mitochondria in both the pathobiology of pulmonary hypertension and potential therapeutic targets in pulmonary vascular processes.

Time-varying, serotype-specific force of infection of dengue virus.

Infectious disease models play a key role in public health planning. These models rely on accurate estimates of key transmission parameters such as the force of infection (FoI), which is the per-capita risk of a susceptible person being infected. The FoI captures the fundamental dynamics of transmission and is crucial for gauging control efforts, such as identifying vaccination targets. Dengue virus (DENV) is a mosquito-borne, multiserotype pathogen that currently infects ∼390 million people a year. Existing estimates of the DENV FoI are inaccurate because they rely on the unrealistic assumption that risk is constant over time. Dengue models are thus unreliable for designing vaccine deployment strategies. Here, we present to our knowledge the first time-varying (daily), serotype-specific estimates of DENV FoIs using a spline-based fitting procedure designed to examine a 12-y, longitudinal DENV serological dataset from Iquitos, Peru (11,703 individuals, 38,416 samples, and 22,301 serotype-specific DENV infections from 1999 to 2010). The yearly DENV FoI varied markedly across time and serotypes (0-0.33), as did daily basic reproductive numbers (0.49-4.72). During specific time periods, the FoI fluctuations correlated across serotypes, indicating that different DENV serotypes shared common transmission drivers. The marked variation in transmission intensity that we detected indicates that intervention targets based on one-time estimates of the FoI could underestimate the level of effort needed to prevent disease. Our description of dengue virus transmission dynamics is unprecedented in detail, providing a basis for understanding the persistence of this rapidly emerging pathogen and improving disease prevention programs.

Racial, Ethnic, and Rural Disparities in US Veteran COVID-19 Vaccine Rates.

Background: Race, ethnicity, and rurality-related disparities in coronavirus disease 2019 (COVID-19) vaccine uptake have been documented in the United States (US). Objective: We determined whether these disparities existed among patients at the Department of Veterans Affairs (VA), the largest healthcare system in the US. Design Settings Participants Measurements: Using VA Corporate Data Warehouse data, we included 5,871,438 patients (9.4% women) with at least one primary care visit in 2019 in a retrospective cohort study. Each patient was assigned a single race/ethnicity, which were mutually exclusive, self-reported categories. Rurality was based on 2019 home address at the zip code level. Our primary outcome was time-to-first COVID-19 vaccination between December 15, 2020-June 15, 2021. Additional covariates included age (in years), sex, geographic region (North Atlantic, Midwest, Southeast, Pacific, Continental), smoking status (current, former, never), Charlson Comorbidity Index (based on ≥1 inpatient or two outpatient ICD codes), service connection (any/none, using standardized VA-cutoffs for disability compensation), and influenza vaccination in 2019-2020 (yes/no). Results: Compared with unvaccinated patients, those vaccinated (n=3,238,532; 55.2%) were older (mean age in years vaccinated=66.3, (standard deviation=14.4) vs. unvaccinated=57.7, (18.0), p<.0001)). They were more likely to identify as Black (18.2% vs. 16.1%, p<.0001), Hispanic (7.0% vs. 6.6% p<.0001), or Asian American/Pacific Islander (AA/PI) (2.0% vs. 1.7%, P<.0001). In addition, they were more likely to reside in urban settings (68.0% vs. 62.8, p<.0001). Relative to non-Hispanic White urban Veterans, the reference group for race/ethnicity-urban/rural hazard ratios reported, all urban race/ethnicity groups were associated with increased likelihood for vaccination except American Indian/Alaskan Native (AI/AN) groups. Urban Black groups were 12% more likely (Hazard Ratio (HR)=1.12 [CI 1.12-1.13]) and rural Black groups were 6% more likely to receive a first vaccination (HR=1.06 [1.05-1.06]) relative to white urban groups. Urban Hispanic, AA/PI and Mixed groups were more likely to receive vaccination while rural members of these groups were less likely (Hispanic: Urban HR=1.17 [1.16-1.18], Rural HR=0.98 [0.97-0.99]; AA/PI: Urban HR=1.22 [1.21-1.23], Rural HR=0.86 [0.84-0.88]). Rural White Veterans were 21% less likely to receive an initial vaccine compared with urban White Veterans (HR=0.79 [0.78-0.79]). AI/AN groups were less likely to receive vaccination regardless of rurality: Urban HR=0.93 [0.91-0.95]; AI/AN-Rural HR=0.76 [0.74-0.78]. Conclusions: Urban Black, Hispanic, and AA/PI Veterans were more likely than their urban White counterparts to receive a first vaccination; all rural race/ethnicity groups except Black patients had lower likelihood for vaccination compared with urban White patients. A better understanding of disparities and rural outreach will inform equitable vaccine distribution.

Direct mosquito feedings on dengue-2 virus-infected people reveal dynamics of human infectiousness.

Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7-16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies.

Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: a prospective, multicentre, cross-sectional diagnostic accuracy study.

BACKGROUND: Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness. METHODS: We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355. FINDINGS: From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes. INTERPRETATION: This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses. FUNDING: BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease.

The pathogenesis of chronic obstructive pulmonary disease (COPD) involves aberrant responses to cellular stress caused by chronic cigarette smoke (CS) exposure. However, not all smokers develop COPD and the critical mechanisms that regulate cellular stress responses to increase COPD susceptibility are not understood. Because microRNAs are well-known regulators of cellular stress responses, we evaluated microRNA expression arrays performed on distal parenchymal lung tissue samples from 172 subjects with and without COPD. We identified miR-24-3p as the microRNA that best correlated with radiographic emphysema and validated this finding in multiple cohorts. In a CS exposure mouse model, inhibition of miR-24-3p increased susceptibility to apoptosis, including alveolar type II epithelial cell apoptosis, and emphysema severity. In lung epithelial cells, miR-24-3p suppressed apoptosis through the BH3-only protein BIM and suppressed homology-directed DNA repair and the DNA repair protein BRCA1. Finally, we found BIM and BRCA1 were increased in COPD lung tissue, and BIM and BRCA1 expression inversely correlated with miR-24-3p. We concluded that miR-24-3p, a regulator of the cellular response to DNA damage, is decreased in COPD, and decreased miR-24-3p increases susceptibility to emphysema through increased BIM and apoptosis.

Feasibility of feeding Aedes aegypti mosquitoes on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru.

BACKGROUND: Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru. METHODOLOGY/PRINCIPAL FINDINGS: Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 10(2) to 2.9 × 10(6) focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were similar across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability.

Hypercoagulability in Pulmonary Hypertension.

Pulmonary hypertension (PH) is divided into varied pathophysiological and etiologic groupings, as classified by the World Health Organization (WHO). Pulmonary arterial hypertension (PAH), which falls under WHO group 1 PH, is a progressive and potentially fatal disease characterized by a vasoconstrictive, proliferative, and thrombotic phenotype, which leads to increased pulmonary artery pressure, right heart failure, and death. Pathologically, in situ thromboses are found in the small distal pulmonary arteries. Dysregulation of coagulation, platelet function, and endothelial cells may contribute to a prothrombotic state. There is mixed evidence for the use of anticoagulation or antiplatelet therapy in PAH patients.

Pulmonary arterial hypertension in the setting of scleroderma is different than in the setting of lupus: A review.

Pulmonary hypertension (PH) is a clinical syndrome that is subdivided into five groups per the World Health Organization (WHO) classification, based largely on hemodynamic and pathophysiologic criteria. WHO Group 1 PH, termed pulmonary arterial hypertension (PAH), is a clinically progressive disease that can eventually lead to right heart failure and death, and it is hemodynamically characterized by pre-capillary PH and increased pulmonary vascular resistance in the absence of elevated left ventricular filling pressures. PAH can be idiopathic, heritable, or associated with a variety of conditions. Connective tissue diseases make up the largest portion of these associated conditions, most commonly systemic sclerosis (SSc), followed by mixed connective tissue disease and systemic lupus erythematous. These etiologies (namely SSc and Lupus) have been grouped together as connective tissue disease-associated PAH, however emerging evidence suggests they differ in pathogenesis, clinical course, prognosis, and treatment response. This review highlights the differences between SSc-PAH and Lupus-PAH. After introducing the diagnosis, screening, and pathobiology of PAH, we discuss connective tissue disease-associated PAH as a group, and then explore SSc-PAH and SLE-PAH separately, comparing these 2 PAH etiologies.

Review of the Ongoing Story of Appetite Suppressants, Serotonin Pathway, and Pulmonary Vascular Disease.

Obesity is pandemic in the Western Hemisphere, especially in the United States (US) and is associated with morbidity and mortality. Recent data show that a large proportion of the US population is at least overweight and almost 2 in 5 Americans are obese. This ongoing trend of increasing obesity rates has led to a thriving market for anorexigens. Despite the health benefits of weight loss, several anorexigens had devastating side effects including pulmonary vascular disease which manifests as the clinical syndrome of pulmonary arterial hypertension (PAH). PAH is an incurable and fatal disease and is characterized by vascular constriction, hypertrophy, and proliferation that over time lead to right-sided cardiac failure. Over the past few decades, several weight loss medications have been associated with the development of PAH, possibly caused by an increase in systemic serotonin levels, resulting in vasoconstriction of the pulmonary arteries and initiating a cascade of pathologic vascular remodeling leading to vascular fibrosis. Once sufficient evidence for the association of these drugs with PAH or other related pathologies was found, many were removed from the market. However, there are other appetite suppressants still currently on the market (whether Food and Drug Administration-approved or "dietary supplements") that have to some extent similar mechanisms of action to those associated with PAH but lack robust enough data to prove or disprove an association. The serotonin pathway seems to be repeatedly implicated. In conclusion, given that PAH is a progressive and debilitating disease, it is important to highlight possible risk factors that could be avoided.

Pulmonary hypertension: diagnostic and therapeutic challenges.

Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic state that can be found in multiple conditions with associated symptoms of dyspnea, decreased exercise tolerance, and progression to right heart failure. The World Health Organization has classified PH into five groups. The first group is pulmonary arterial hypertension (PAH), which can be idiopathic, heritable, due to drugs and toxins, or associated with conditions such as connective tissue diseases, congenital heart disease, portal hypertension, and others. The development of PAH is believed to result from smooth muscle cells and endothelial dysfunction that impairs production of vasodilators, including nitric oxide and prostacyclin. The importance of distinguishing this group from the other groups of PH is that there are PAH-specific drugs that target the molecular pathways that are pathogenic in the vascular derangements, leading to arterial hypertension, which should not be used in the other forms of PH. Other groups of PH include PH due to left heart disease, lung disease, chronic thromboembolic disease, as well as a miscellaneous category. Echocardiography is used to screen for PH and has varying sensitivity and specificity in detecting PH. Additionally, the right heart pressures estimated during echocardiogram often differ from those obtained during confirmatory testing with right heart catheterization. The most challenging PH diagnosis is in a case that does not fit one group of PH, but meets criteria that overlap between several groups. This also makes the treatment challenging because each group of PH is managed differently. This review provides an overview of the five groups of PH and discusses the diagnostic and therapeutic challenges of each.

[Lessons learned in the control of Aedes aegypti to address dengue and the emergency of chikungunya in Iquitos, Peru]. / Lecciones aprendidas en el control de Aedes aegypti para afrontar el dengue y la emergencia de chikungunya en Iquitos, Perú.

Dengue has affected Iquitos since 1990 causing outbreaks of major impact on public health and for this reason great efforts have been made for its temporal control. Currently, with the expansion of the chikungunya virus in the Americas and the threat of the emergence of the virus in Iquitos, we reflect on lessons learned by way of the activities undertaken in the area of vector control; epidemiological surveillance, diagnosis and clinical management during periods of outbreaks of dengue, in a way that will allow us to better face the threat of an outbreak of chikungunya virus in the largest city in the Peruvian Amazon.