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1.
Nat Immunol ; 22(6): 781-793, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34031617

RESUMO

Multimodal T cell profiling can enable more precise characterization of elusive cell states underlying disease. Here, we integrated single-cell RNA and surface protein data from 500,089 memory T cells to define 31 cell states from 259 individuals in a Peruvian tuberculosis (TB) progression cohort. At immune steady state >4 years after infection and disease resolution, we found that, after accounting for significant effects of age, sex, season and genetic ancestry on T cell composition, a polyfunctional type 17 helper T (TH17) cell-like effector state was reduced in abundance and function in individuals who previously progressed from Mycobacterium tuberculosis (M.tb) infection to active TB disease. These cells are capable of responding to M.tb peptides. Deconvoluting this state-uniquely identifiable with multimodal analysis-from public data demonstrated that its depletion may precede and persist beyond active disease. Our study demonstrates the power of integrative multimodal single-cell profiling to define cell states relevant to disease and other traits.


Assuntos
Memória Imunológica , Mycobacterium tuberculosis/imunologia , Células Th17/imunologia , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Progressão da Doença , Feminino , Seguimentos , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Peru , RNA-Seq , Fatores Sexuais , Análise de Célula Única , Fatores Socioeconômicos , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/microbiologia , Adulto Jovem
2.
Nature ; 620(7975): 824-829, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532931

RESUMO

The fossil record of cetaceans documents how terrestrial animals acquired extreme adaptations and transitioned to a fully aquatic lifestyle1,2. In whales, this is associated with a substantial increase in maximum body size. Although an elongate body was acquired early in cetacean evolution3, the maximum body mass of baleen whales reflects a recent diversification that culminated in the blue whale4. More generally, hitherto known gigantism among aquatic tetrapods evolved within pelagic, active swimmers. Here we describe Perucetus colossus-a basilosaurid whale from the middle Eocene epoch of Peru. It displays, to our knowledge, the highest degree of bone mass increase known to date, an adaptation associated with shallow diving5. The estimated skeletal mass of P. colossus exceeds that of any known mammal or aquatic vertebrate. We show that the bone structure specializations of aquatic mammals are reflected in the scaling of skeletal fraction (skeletal mass versus whole-body mass) across the entire disparity of amniotes. We use the skeletal fraction to estimate the body mass of P. colossus, which proves to be a contender for the title of heaviest animal on record. Cetacean peak body mass had already been reached around 30 million years before previously assumed, in a coastal context in which primary productivity was particularly high.


Assuntos
Adaptação Fisiológica , Evolução Biológica , Peso Corporal , Fósseis , Baleias , Animais , Aclimatação , Peru , Baleias/anatomia & histologia , Baleias/classificação , Baleias/fisiologia , Tamanho Corporal , Esqueleto , Mergulho
3.
Nature ; 606(7912): 120-128, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35545678

RESUMO

Non-coding genetic variants may cause disease by modulating gene expression. However, identifying these expression quantitative trait loci (eQTLs) is complicated by differences in gene regulation across fluid functional cell states within cell types. These states-for example, neurotransmitter-driven programs in astrocytes or perivascular fibroblast differentiation-are obscured in eQTL studies that aggregate cells1,2. Here we modelled eQTLs at single-cell resolution in one complex cell type: memory T cells. Using more than 500,000 unstimulated memory T cells from 259 Peruvian individuals, we show that around one-third of 6,511 cis-eQTLs had effects that were mediated by continuous multimodally defined cell states, such as cytotoxicity and regulatory capacity. In some loci, independent eQTL variants had opposing cell-state relationships. Autoimmune variants were enriched in cell-state-dependent eQTLs, including risk variants for rheumatoid arthritis near ORMDL3 and CTLA4; this indicates that cell-state context is crucial to understanding potential eQTL pathogenicity. Moreover, continuous cell states explained more variation in eQTLs than did conventional discrete categories, such as CD4+ versus CD8+, suggesting that modelling eQTLs and cell states at single-cell resolution can expand insight into gene regulation in functionally heterogeneous cell types.


Assuntos
Predisposição Genética para Doença , Células T de Memória , Locos de Características Quantitativas , Regulação da Expressão Gênica , Predisposição Genética para Doença/genética , Humanos , Células T de Memória/imunologia , Células T de Memória/metabolismo , Peru , Locos de Características Quantitativas/genética
4.
PLoS Genet ; 20(6): e1011313, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38870230

RESUMO

A quarter of humanity is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses to Mtb infection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n = 63) or did not progress to TB (controls, n = 63). Transcriptomic profiling of monocyte-derived DCs and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Four genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was with FAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism. FAH expression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data of Mtb-infected monocyte-derived dendritic cells, we found that Mtb infection results in FAH downregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.


Assuntos
Células Dendríticas , Macrófagos , Mycobacterium tuberculosis , Locos de Características Quantitativas , Tuberculose , Humanos , Peru , Tuberculose/genética , Tuberculose/microbiologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Mycobacterium tuberculosis/patogenicidade , Mycobacterium tuberculosis/genética , Feminino , Células Dendríticas/metabolismo , Masculino , Adulto , Predisposição Genética para Doença , Variação Genética , Regulação da Expressão Gênica , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Perfilação da Expressão Gênica
5.
Nature ; 582(7811): 234-239, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32499652

RESUMO

On average, Peruvian individuals are among the shortest in the world1. Here we show that Native American ancestry is associated with reduced height in an ethnically diverse group of Peruvian individuals, and identify a population-specific, missense variant in the FBN1 gene (E1297G) that is significantly associated with lower height. Each copy of the minor allele (frequency of 4.7%) reduces height by 2.2 cm (4.4 cm in homozygous individuals). To our knowledge, this is the largest effect size known for a common height-associated variant. FBN1 encodes the extracellular matrix protein fibrillin 1, which is a major structural component of microfibrils. We observed less densely packed fibrillin-1-rich microfibrils with irregular edges in the skin of individuals who were homozygous for G1297 compared with individuals who were homozygous for E1297. Moreover, we show that the E1297G locus is under positive selection in non-African populations, and that the E1297 variant shows subtle evidence of positive selection specifically within the Peruvian population. This variant is also significantly more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru.


Assuntos
Estatura/genética , Fibrilina-1/genética , Mutação de Sentido Incorreto , Seleção Genética , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Hereditariedade , Humanos , Indígenas Sul-Americanos/genética , Masculino , Microfibrilas/química , Microfibrilas/genética , Peru
6.
Am J Hum Genet ; 109(6): 1117-1139, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35588731

RESUMO

Preeclampsia is a multi-organ complication of pregnancy characterized by sudden hypertension and proteinuria that is among the leading causes of preterm delivery and maternal morbidity and mortality worldwide. The heterogeneity of preeclampsia poses a challenge for understanding its etiology and molecular basis. Intriguingly, risk for the condition increases in high-altitude regions such as the Peruvian Andes. To investigate the genetic basis of preeclampsia in a population living at high altitude, we characterized genome-wide variation in a cohort of preeclamptic and healthy Andean families (n = 883) from Puno, Peru, a city located above 3,800 meters of altitude. Our study collected genomic DNA and medical records from case-control trios and duos in local hospital settings. We generated genotype data for 439,314 SNPs, determined global ancestry patterns, and mapped associations between genetic variants and preeclampsia phenotypes. A transmission disequilibrium test (TDT) revealed variants near genes of biological importance for placental and blood vessel function. The top candidate region was found on chromosome 13 of the fetal genome and contains clotting factor genes PROZ, F7, and F10. These findings provide supporting evidence that common genetic variants within coagulation genes play an important role in preeclampsia. A selection scan revealed a potential adaptive signal around the ADAM12 locus on chromosome 10, implicated in pregnancy disorders. Our discovery of an association in a functional pathway relevant to pregnancy physiology in an understudied population of Native American origin demonstrates the increased power of family-based study design and underscores the importance of conducting genetic research in diverse populations.


Assuntos
Pré-Eclâmpsia , Altitude , Fatores de Coagulação Sanguínea , Proteínas Sanguíneas/genética , Estudos de Casos e Controles , Fator VII/genética , Fator X/genética , Feminino , Humanos , Peru/epidemiologia , Placenta , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/genética , Gravidez
7.
Am J Respir Crit Care Med ; 210(2): 222-233, 2024 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-38416532

RESUMO

Rationale: The persistent burden of tuberculosis (TB) disease emphasizes the need to identify individuals with TB for treatment and those at a high risk of incident TB for prevention. Targeting interventions toward those at high risk of developing and transmitting TB is a public health priority. Objectives: We aimed to identify characteristics of individuals involved in TB transmission in a community setting, which may guide the prioritization of targeted interventions. Methods: We collected clinical and sociodemographic data from a cohort of patients with TB in Lima, Peru. We used whole-genome sequencing data to assess the genetic distance between all possible pairs of patients; we considered pairs to be the result of a direct transmission event if they differed by three or fewer SNPs, and we assumed that the first diagnosed patient in a pair was the transmitter and the second was the recipient. We used logistic regression to examine the association between host factors and the likelihood of direct TB transmission. Measurements and Main Results: Analyzing data from 2,518 index patients with TB, we identified 1,447 direct transmission pairs. Regardless of recipient attributes, individuals less than 34 years old, males, and those with a history of incarceration had a higher likelihood of being transmitters in direct transmission pairs. Direct transmission was more likely when both patients were drinkers or smokers. Conclusions: This study identifies men, young adults, former prisoners, alcohol consumers, and smokers as priority groups for targeted interventions. Innovative strategies are needed to extend TB screening to social groups such as young adults and prisoners with limited access to routine preventive care.


Assuntos
Tuberculose , Humanos , Peru/epidemiologia , Masculino , Feminino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Coortes , Tuberculose/transmissão , Tuberculose/epidemiologia , Adolescente , Fatores de Risco , Sequenciamento Completo do Genoma , Idoso
8.
Proc Natl Acad Sci U S A ; 119(51): e2216843119, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36512498

RESUMO

So far in this century, six very large-magnitude earthquakes (MW ≥ 7.8) have ruptured separate portions of the subduction zone plate boundary of western South America along Ecuador, Peru, and Chile. Each source region had last experienced a very large earthquake from 74 to 261 y earlier. This history led to their designation in advance as seismic gaps with potential to host future large earthquakes. Deployments of geodetic and seismic monitoring instruments in several of the seismic gaps enhanced resolution of the subsequent faulting processes, revealing preevent patterns of geodetic slip deficit accumulation and heterogeneous coseismic slip on the megathrust fault. Localized regions of large slip, or asperities, appear to have influenced variability in how each source region ruptured relative to prior events, as repeated ruptures have had similar, but not identical slip distributions. We consider updated perspectives of seismic gaps, asperities, and geodetic locking to assess current very large earthquake hazard along the South American subduction zone, noting regions of particular concern in northern Ecuador and Colombia (1958/1906 rupture zone), southeastern Peru (southeasternmost 1868 rupture zone), north Chile (1877 rupture zone), and north-central Chile (1922 rupture zone) that have large geodetic slip deficit measurements and long intervals (from 64 to 154 y) since prior large events have struck those regions. Expanded geophysical measurements onshore and offshore in these seismic gaps may provide critical information about the strain cycle and fault stress buildup late in the seismic cycle in advance of the future great earthquakes that will eventually strike each region.


Assuntos
Terremotos , Chile , Equador , Peru , Colômbia
9.
Proc Natl Acad Sci U S A ; 119(40): e2116446119, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36161957

RESUMO

Monitoring the status of species is crucial for biodiversity conservation and sustainable resource management in tropical forests, but conventional in situ monitoring methods are impractical over large scales. Scientists have resorted to two potentially complementary approaches: local ecological knowledge (LEK) and remote sensing. To gauge the potential of combining LEK and remote sensing for assessing species status at landscape scales, a large-scale assessment of the reliability of both measures is critical but hampered by the lack of ground-level data. We conducted a landscape-scale assessment of LEK and remote sensing, using a survey of over 900 communities (a near census in our study area) and nearly 4,000 households in 235 randomly selected communities in the Peruvian Amazon-the largest LEK survey as yet undertaken in tropical forests. The survey collected LEK data on the presence of 20 indicator species from both community leaders/elders and randomly sampled households. We assessed LEK and remotely sensed land cover-forest cover and nonmain channel open water-as proxies for species habitat, across species (game, fish, and timber), over time (current and historical), and by indigeneity (Indigenous peoples and mestizos). Overall, LEK and remotely sensed land cover corroborate each other well. Concordance is highest for the current status of game species reported by sampled households, as is the concordance of historical LEK from Indigenous community leaders/elders. The results point to the promise of combining LEK and remote sensing in monitoring the status of species in data-poor tropical forests.


Assuntos
Florestas , Tecnologia de Sensoriamento Remoto , Animais , Biodiversidade , Conservação dos Recursos Naturais , Ecossistema , Peru , Reprodutibilidade dos Testes , Clima Tropical , Água
10.
Proc Natl Acad Sci U S A ; 119(45): e2207022119, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36322726

RESUMO

Spatially targeted interventions may be effective alternatives to individual or population-based prevention strategies against tuberculosis (TB). However, their efficacy may depend on the mechanisms that lead to geographically constrained hotspots. Local TB incidence may reflect high levels of local transmission; conversely, they may point to frequent travel of community members to high-risk areas. We used whole-genome sequencing to explore patterns of TB incidence and transmission in Lima, Peru. Between 2009 and 2012, we recruited incident pulmonary TB patients and their household contacts, whom we followed for the occurrence of TB disease. We used whole-genome sequences of 2,712 Mycobacterial tuberculosis isolates from 2,440 patients to estimate pariwise genomic distances and compared these to the spatial distance between patients' residences. Genomic distances increased rapidly as spatial distances increased and remained high beyond 2 km of separation. Next, we divided the study catchment area into 1 × 1 km grid-cell surface units and used household spatial coordinates to locate each TB patient to a specific cell. We estimated cell-specific transmission by calculating the proportion of patients in each cell with a pairwise genomic distance of 10 or fewer single-nucleotide polymorphisms. We found that cell-specific TB incidence and local transmission varied widely but that cell-specific TB incidence did not correlate closely with our estimates of local transmission (Cohen's k = 0.27). These findings indicate that an understanding of the spatial heterogeneity in the relative proportion of TB due to local transmission may help guide the implementation of spatially targeted interventions.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Humanos , Peru/epidemiologia , Tuberculose/epidemiologia , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Sequenciamento Completo do Genoma
11.
Proc Natl Acad Sci U S A ; 119(26): e2118283119, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35737833

RESUMO

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.


Assuntos
Aedes , Repelentes de Insetos , Controle de Mosquitos , Mosquitos Vetores , Doenças Transmitidas por Vetores , Adulto , Animais , Dengue/epidemiologia , Dengue/prevenção & controle , Humanos , Controle de Mosquitos/normas , Peru/epidemiologia , Doenças Transmitidas por Vetores/epidemiologia , Doenças Transmitidas por Vetores/prevenção & controle , Doenças Transmitidas por Vetores/transmissão , Zika virus , Infecção por Zika virus
12.
J Infect Dis ; 229(3): 845-854, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-37584273

RESUMO

BACKGROUND: Neisseria gonorrheae and Chlamydia trachomatis are associated with mucosal inflammation and human immunodeficiency virus 1 (HIV-1) transmission. We assessed levels of inflammatory cytokines in men who have sex with men (MSM) with and without rectal gonorrhea and/or chlamydia in Lima, Peru. METHODS: We screened 605 MSM reporting condomless receptive anal intercourse for rectal N. gonorrheae/C. trachomatis using nucleic acid testing. We identified 101 cases of gonorrhea and/or chlamydia and randomly selected 50 N. gonorrheae/C. trachomatis positive cases and matched 52 negative controls. We measured levels of IL-1ß, IL-6, IL-8, and TNF-α in rectal secretions. Tests for HIV-1, rectal N. gonorrheae/C. trachomatis, and mucosal cytokines were repeated after 3 and 6 months. Cytokine levels in cases and uninfected controls were compared using Wilcoxon rank-sum tests and linear regression. RESULTS: MSM with gonorrhea/chlamydia had elevated levels of all cytokines in rectal mucosa compared with matched controls (all P values <.001). Following antibiotic treatment there were no significant differences in cytokine levels at 3- or 6-month follow-up evaluations (all P values >.05). DISCUSSION: Rectal gonorrhea/chlamydia infection is associated with transient mucosal inflammation and cytokine recruitment. Our data provide proof of concept for rectal sexually transmitted infection screening as an HIV prevention strategy for MSM. Clinical Trials Registration. NCT03010020.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , HIV-1 , Doenças Retais , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Gonorreia/diagnóstico , Chlamydia trachomatis , Citocinas , Peru/epidemiologia , Neisseria gonorrhoeae , Infecções por Chlamydia/diagnóstico , Doenças Retais/epidemiologia , Mucosa , Inflamação , Infecções por HIV/tratamento farmacológico , Prevalência
13.
Emerg Infect Dis ; 30(10): 2211-2214, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39320235

RESUMO

Fort Sherman virus (FSV) was isolated in Panama in 1985 from a US soldier. We report a case of human FSV infection in a febrile patient from northern coastal Peru in 2020. FSV infections spanning ≈35 years and a distance of 2,000 km warrant diagnostics, genomic surveillance, and investigation of transmission cycles.


Assuntos
Filogenia , Humanos , Peru/epidemiologia , Masculino , Adulto , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/virologia , História do Século XXI
14.
Emerg Infect Dis ; 30(11): 2432-2435, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39447191

RESUMO

We report a suspected case of acute pulmonary coccidioidomycosis contracted in Peru, where the disease is not known to occur, in a patient from Switzerland. Although not confirmed by direct diagnostic testing, the clinical manifestations and serologic testing results of this case are highly suggestive of coccidioidomycosis.


Assuntos
Coccidioidomicose , Pneumopatias Fúngicas , Viagem , Humanos , Coccidioidomicose/diagnóstico , Coccidioidomicose/tratamento farmacológico , Coccidioidomicose/microbiologia , Peru , Suíça , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/microbiologia , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Doença Aguda , Coccidioides/isolamento & purificação , Adulto , Pessoa de Meia-Idade
15.
Emerg Infect Dis ; 30(6): 1115-1124, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781680

RESUMO

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.


Assuntos
Características da Família , Programas de Rastreamento , Radiografia Torácica , Humanos , Peru/epidemiologia , Masculino , Feminino , Adulto , Adolescente , Adulto Jovem , Programas de Rastreamento/métodos , Estudos Longitudinais , Pessoa de Meia-Idade , Criança , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/diagnóstico por imagem , Busca de Comunicante/métodos , Pré-Escolar , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Tuberculose Latente/diagnóstico por imagem , Lactente , Tuberculose/epidemiologia , Tuberculose/diagnóstico , Tuberculose/diagnóstico por imagem
16.
N Engl J Med ; 385(25): 2348-2360, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34587382

RESUMO

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. CONCLUSIONS: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).


Assuntos
COVID-19/prevenção & controle , ChAdOx1 nCoV-19 , Eficácia de Vacinas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , ChAdOx1 nCoV-19/efeitos adversos , Chile/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Imunogenicidade da Vacina , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Estados Unidos/epidemiologia , Adulto Jovem
17.
Ann Surg Oncol ; 31(9): 6097-6117, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38888862

RESUMO

INTRODUCTION: The worldwide incidence of melanoma has increased in the last 40 years. Our aim was to describe the clinic-pathological characteristics and outcomes of three cohorts of patients diagnosed with melanoma in a Latin-American cancer institute during the last 20 years. METHODS: We evaluated three retrospective patient cohorts diagnosed with melanoma at Instituto Nacional de Enfermedades Neoplasicas (INEN), a public hospital in Lima, Peru, for the years 2005-2006, 2010-2011, and 2017-2018. Survival rate differences were assessed using the Log-rank test. RESULTS: Overall, 584 patients were included (only trunk and extremities); 51% were male, the mean age was 61 (3-97) years, and 48% of patients resided in rural areas. The mean time to diagnosis was 22.6 months, and the mean Breslow thickness was 7.4 mm (T4). Lower extremity was the most common location (72%). A majority of the patients (55%) had metastases at the time of presentation, with 36% in stage III and 19% in stage IV. Cohorts were distributed as 2005-2006 (n = 171), 2010-2011 (n = 223), and 2017-2018 (n = 190). No immunotherapy was used. Cohort C exhibited the most significant increase in stage IV diagnoses (12.3%, 15.7%, 28.4%, respectively; p < 0.01). The median overall survival rates at the three-year follow-up demonstrated a decline over the years for stages II (97%, 98%, 57%, respectively; p < 0.05) and III (66%, 77%, 37%; p < 0.01). CONCLUSIONS: There has been a worsening in the incidence of late-stage metastatic melanoma in Peru throughout the years, coupled with a significant decline in overall survival rates. This is underscored by the fact that half of the population lives in regions devoid of oncological access.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Melanoma/epidemiologia , Melanoma/mortalidade , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Retrospectivos , Taxa de Sobrevida , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Peru/epidemiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/epidemiologia , Seguimentos , Criança , Pré-Escolar , Prognóstico , Incidência , Disparidades em Assistência à Saúde , América Latina/epidemiologia
18.
Glob Chang Biol ; 30(8): e17436, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39162201

RESUMO

Measurements of net primary productivity (NPP) and litter decomposition from tropical peatlands are severely lacking, limiting our ability to parameterise and validate models of tropical peatland development and thereby make robust predictions of how these systems will respond to future environmental and climatic change. Here, we present total NPP (i.e., above- and below-ground) and decomposition data from two floristically and structurally distinct forested peatland sites within the Pastaza Marañón Foreland Basin, northern Peru, the largest tropical peatland area in Amazonia: (1) a palm (largely Mauritia flexuosa) dominated swamp forest and (2) a hardwood dominated swamp forest (known as 'pole forest', due to the abundance of thin-stemmed trees). Total NPP in the palm forest and hardwood-dominated forest (9.83 ± 1.43 and 7.34 ± 0.84 Mg C ha-1 year-1, respectively) was low compared with values reported for terra firme forest in the region (14.21-15.01 Mg C ha-1 year-1) and for tropical peatlands elsewhere (11.06 and 13.20 Mg C ha-1 year-1). Despite the similar total NPP of the two forest types, there were considerable differences in the distribution of NPP. Fine root NPP was seven times higher in the palm forest (4.56 ± 1.05 Mg C ha-1 year-1) than in the hardwood forest (0.61 ± 0.22 Mg C ha-1 year-1). Above-ground palm NPP, a frequently overlooked component, made large contributions to total NPP in the palm-dominated forest, accounting for 41% (14% in the hardwood-dominated forest). Conversely, Mauritia flexuosa litter decomposition rates were the same in both plots: highest for leaf material, followed by root and then stem material (21%, 77% and 86% of mass remaining after 1 year respectively for both plots). Our results suggest potential differences in these two peatland types' responses to climate and other environmental changes and will assist in future modelling studies of these systems.


Mediciones de la productividad primaria neta (PPN) y la descomposición de materia orgánica de las turberas tropicales son escasas, lo que limita nuestra capacidad para parametrizar y validar modelos de desarrollo de las turberas tropicales y, en consecuencia, realizar predicciones sólidas sobre la respuesta de estos sistemas ante futuros cambios ambientales y climáticos. En este estudio, presentamos datos de PPN total (es decir, biomasa aérea y subterránea) y descomposición de la materia orgánica colectada en dos turberas boscosas con características florísticas y estructurales contrastantes dentro de la cuenca Pastaza Marañón al norte del Perú, el área de turberas tropicales más grande de la Amazonia: (1) un bosque pantanoso dominado por palmeras (principalmente Mauritia flexuosa) y (2) un bosque pantanosos dominado por árboles leñosos de tallo delgado (conocido como 'varillal hidromórfico'). La PPN total en el bosque de palmeras y el varillal hidromórfico (9,83 ± 1,43 y 7,34 ± 0,84 Mg C ha­1 año­1 respectivamente) fue baja en comparación con los valores reportados para los bosques de tierra firme en la región (14,21­15,01 Mg C ha­1 año­1) y para turberas tropicales en otros lugares (11,06 y 13,20 Mg C ha­1 año­1). A pesar de que la PPN total fue similar en ambos tipos de bosque, hubo diferencias considerables en la distribución de la PPN. La PPN de las raíces finas fue siete veces mayor en el bosque de palmeras (4,56 ± 1,05 Mg C ha­1 año­1) que en el varillal hidromórfico (0,61 ± 0,22 Mg C ha­1 año­1). La PPN de la biomasa aérea de las palmeras, un componente ignorado frecuentemente, contribuyó en gran medida a la PPN total del bosque de palmeras, representando el 41% (14% en el varillal hidromórfico). Por el contrario, la tasa de descomposición de materia orgánica de Mauritia flexuosa fue la misma en ambos sitios: la más alta corresponde a la hojarasca, seguida por las raíces y luego el tallo (21%, 77% y 86% de la masa restante después de un año, respectivamente para ambos sitios). Nuestros resultados sugieren diferencias potenciales en la respuesta de estos dos tipos de turberas al clima y otros cambios ambientales, y ayudarán en futuros estudios de modelamiento de estos sistemas.


Assuntos
Florestas , Peru , Áreas Alagadas , Solo/química , Folhas de Planta/metabolismo , Clima Tropical
19.
Sex Transm Infect ; 100(2): 84-90, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38124224

RESUMO

OBJECTIVES: Sexual networks are known to structure sexually transmitted infection (STI) transmission among men who have sex with men (MSM). We sought to estimate the risks of STI diagnosis for various partnership types within these networks. METHODS: Our cross-sectional survey analysed data from 1376 MSM screened for a partner management intervention in Lima, Peru. Participants were tested for HIV, syphilis, gonorrhoea (NG) and chlamydia (CT) and completed surveys on their demographics, sexual identity/role, HIV status, partnership types and sexual network from the prior 90 days. χ2 and Wilcoxon rank-sum tests compared participants without an STI to those diagnosed with (1) syphilis, (2) NG and/or CT (NG/CT) and (3) syphilis and NG/CT coinfection (coinfection). RESULTS: 40.8% (n=561/1376) of participants were diagnosed with an STI (syphilis: 14.9%, NG/CT: 16.4%, coinfection: 9.5%). 47.9% of all participants were living with HIV and 8.9% were newly diagnosed. A greater proportion of participants with syphilis and coinfection were living with HIV (73.5%, p<0.001; 71.0%, p<0.001) compared with those with NG/CT (47.8%) or no STI (37.8%). Participants with syphilis more often reported sex-on-premises venues (SOPVs) as the location of their last sexual encounter (51.7%, p=0.038) while those with NG/CT tended to meet their last sexual partner online (72.8%, p=0.031). Respondents with coinfection were the only STI group more likely to report transactional sex than participants without an STI (31.3%, p=0.039). CONCLUSIONS: Sexual networks and partnership types of Peruvian MSM are associated with differential risks for STIs. Participants diagnosed with syphilis tended to meet single-encounter casual partners at SOPV, while MSM with NG/CT were younger and often contacted casual partners online. Coinfection had higher frequency of transactional sex. These findings suggest the potential importance of public health interventions through combined syphilis/HIV screening at SOPV, syphilis screening at routine clinic appointments for MSM living with HIV and directed advertisements and/or access to NG/CT testing through online platforms.


Assuntos
Chlamydia , Coinfecção , Gonorreia , Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Gonorreia/epidemiologia , Gonorreia/diagnóstico , Sífilis/epidemiologia , Sífilis/diagnóstico , Homossexualidade Masculina , Peru/epidemiologia , Estudos Transversais , Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Parceiros Sexuais
20.
Sex Transm Dis ; 51(6): 415-419, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38372543

RESUMO

BACKGROUND: We aimed to compare the clinical presentations (symptomatic vs. asymptomatic) with prior Treponema pallidum infection status (first infection vs. reinfection) among people with early syphilis. METHODS: We used data from PICASSO, a cohort study in Peru that enrolled people with active syphilis from May 2019 to August 2021. Study participants had early syphilis and a prior syphilis serological test result within the prior 12 months to determine prior T. pallidum infection status. We calculated prevalence ratios (PRs) of symptomatic clinical presentation (primary or secondary syphilis) by prior T. pallidum infection status, stratified by HIV infection status. In addition, we explored the association of prior T. pallidum infection status and lesion presentation, stratified by primary and secondary syphilis cases, using the Fisher exact test. RESULTS: We include 84 T. pallidum reinfection cases and 61 first infection cases. We found increased frequency of symptomatic clinical presentation among first-infection cases (39% vs. 20%; PR, 1.94; P = 0.014). This association was stronger among persons living without HIV infection (38% vs. 7%; adjusted PR, 6.63; P = 0.001) in comparison to those living with HIV infection (45% vs. 34%; adjusted PR, 1.38; P = 0.458). Among secondary syphilis cases, more participants from the reinfection group reported that their lesions improved 1 week after treatment (100% vs. 29%, P = 0.045) compared with those with a first infection. Among the primary syphilis cases, all participants reported that their lesions improved 1 week after treatment. CONCLUSIONS: Prior syphilis was associated with a decreased prevalence of symptomatic reinfection, especially among persons not living with HIV infection.


Assuntos
Infecções por HIV , Sífilis , Treponema pallidum , Humanos , Sífilis/epidemiologia , Sífilis/complicações , Sífilis/diagnóstico , Peru/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Masculino , Adulto , Feminino , Treponema pallidum/isolamento & purificação , Treponema pallidum/imunologia , Prevalência , Estudos de Coortes , Reinfecção/epidemiologia , Pessoa de Meia-Idade , Adulto Jovem
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