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Strengthening genomic surveillance for neglected tropical diseases in the Americas 加强美洲被忽视热带病的基因组监测
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-12-01 DOI: 10.1016/j.lana.2025.101338
The Lancet Regional Health – Americas
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引用次数: 0
Refugee healthcare resilience and burdens: a 10-year mixed-methods analysis of system shocks in Canada 难民医疗复原力和负担:加拿大10年系统冲击混合方法分析
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-12-01 DOI: 10.1016/j.lana.2025.101279
Eric Norrie , Linda Holdbrook , Rabina Grewal , Rachel Talavlikar , Mohammad Yasir Essar , Tyler Williamson , Annalee Coakley , Kerry McBrien , Gabriel E. Fabreau

Background

System shocks, including policy changes, refugee surges, and pandemics, strain healthcare systems. These shocks compound refugee health vulnerabilities, limiting care but may also trigger adaptive responses that build resilience. Understanding local responses is essential for resilient care models.

Methods

This sequential explanatory mixed-methods retrospective study (2011–2020) examined how a refugee health centre in Alberta, Canada, responded to four shocks: Interim Federal Health Program (IFHP) Cuts (2012), Syrian Surge (2015), Yazidi Resettlement (2017), and COVID-19 (2020). We hypothesized that each shock would drive temporary utilization changes, reflected in level (immediate) and slope (monthly rate of change) shifts, with corresponding impacts on patients and providers. Interrupted time series analysis estimated level and slope differences in monthly appointments (total, family physician, specialist, multidisciplinary team). Interviews with health centre leaders were thematically analyzed using an adapted Health System Resilience framework and integrated with quantitative findings to assess resilience and operational burdens.

Findings

Between 2011 and 2020, 10,661 refugees from 106 countries attended 107,642 appointments. The mean age was 24.49 years (SD 17.09; range 0–107), and 47.82% (5094) were female. Mean monthly appointments increased from 455 to 2,208, with an adjusted level difference of +1656.06 and slope increase of +95.68 (p < 0.0.01). Family physician and multidisciplinary team appointments rose substantially, while specialist care declined during COVID-19. Mean provider hours increased from 175.8 to 1097.3 (6.2-fold). Qualitative analysis indicated resilience capacities but also burnout, vicarious trauma, and financial strain. Integration revealed the centre developed resilience but experienced operational burden.

Interpretation

Over a decade, the centre adapted to successive shocks, transforming into a beacon clinic. It demonstrated resilience through care expansion and innovation, at the cost of operational burden.

Funding

O'Brien Institute for Public Health and the MSI Foundation of Alberta.
系统冲击,包括政策变化、难民潮和流行病,给卫生保健系统带来压力。这些冲击加剧了难民的健康脆弱性,限制了护理,但也可能引发建立复原力的适应性反应。了解当地的反应对于弹性护理模式至关重要。方法本顺序解释性混合方法回顾性研究(2011-2020年)考察了加拿大阿尔伯塔省的一个难民保健中心如何应对四种冲击:临时联邦卫生计划(IFHP)削减(2012年)、叙利亚难民激增(2015年)、雅兹迪人重新安置(2017年)和COVID-19(2020年)。我们假设每次冲击都会导致临时的利用变化,反映在水平(即时)和斜率(每月变化率)变化上,对患者和提供者产生相应的影响。中断时间序列分析估计了每月就诊的水平和斜率差异(总数、家庭医生、专科医生、多学科团队)。对卫生中心领导人的访谈进行了主题分析,使用了经过调整的卫生系统弹性框架,并与定量调查结果相结合,以评估弹性和运营负担。2011年至2020年期间,来自106个国家的10661名难民参加了107642次预约。平均年龄24.49岁(SD 17.09,范围0 ~ 107),女性5094例,占47.82%。平均每月就诊人数从455人增加到2208人,调整后水平差为+1656.06,斜率增加为+95.68 (p < 0.0.01)。在COVID-19期间,家庭医生和多学科团队的任命大幅增加,而专科护理则有所下降。平均医生工作时间从175.8小时增加到1097.3小时(6.2倍)。定性分析表明恢复能力,但倦怠,替代创伤和财务压力。整合表明,该中心发展了弹性,但经历了运营负担。十多年来,该中心适应了连续的冲击,转变为一个灯塔诊所。它以业务负担为代价,通过扩大护理和创新展示了复原力。FundingO'Brien公共卫生研究所和阿尔伯塔MSI基金会。
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引用次数: 0
Respiratory syncytial virus prevention in infants and equity in Latin America and the Caribbean: from evidence to action 拉丁美洲和加勒比婴儿呼吸道合胞体病毒预防与公平性:从证据到行动
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-12-01 DOI: 10.1016/j.lana.2025.101316
María L. Avila-Aguero , Luiza Helena Falleiros-Arlant , José Brea , Carlos Espinal , Flor Muñoz
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引用次数: 0
HEARTS quality: a policy framework to strengthen hypertension and cardiovascular risk management in primary healthcare—insights from HEARTS in the Americas HEARTS质量:在初级卫生保健中加强高血压和心血管风险管理的政策框架——来自美洲HEARTS的见解
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-12-01 DOI: 10.1016/j.lana.2025.101311
Esteban Londoño , Reena Gupta , Patrick Van der Stuyft , Martin Heine , Gloria Giraldo , Grace Marie Ku , Jeffrey Brettler , Andrés Rosende , Vilma Irazola , Jerry Toelsie , Carolina Neira , Teresa Aumala , Yamilé Valdés , Eric Zúñiga , Libardo Rodríguez , Matías Villatoro , María Cristina Escobar , Vivian Pérez , Alied Bencomo , Michael Pereira , Pedro Ordunez
HEARTS in the Americas is the largest-scale implementation of the WHO's global initiative, with 33 countries participating, 28 having adopted standardized clinical pathways, and about 10,000 primary healthcare facilities engaged. Despite progress, fragmented care, limited availability of validated blood pressure devices, restricted access to essential medicines, and weak quality assurance systems continue to hinder hypertension control and cardiovascular risk management. In response, PAHO and participating countries co-developed the HEARTS Quality Framework. Grounded in regional implementation, this model synthesizes global evidence and lessons from Latin America and the Caribbean. Co-designed by Ministries of Health, care providers, and international experts, it translates HEARTS strategies into actionable system-level objectives. Clearly defined outcome indicators and implementation targets promote institutionalization, quality improvement, and primary healthcare strengthening—supporting HEARTS scale-up and equitable outcomes. With appropriate contextualization, the HEARTS Quality Framework provides a practical roadmap for countries beyond the Region to advance primary healthcare-based chronic disease care.
美洲的HEARTS是对世卫组织全球倡议的最大规模实施,有33个国家参与,28个国家采用了标准化临床途径,约有1万个初级卫生保健机构参与。尽管取得了进展,但分散的护理、有限的有效血压装置、有限的基本药物获取以及薄弱的质量保证系统继续阻碍着高血压控制和心血管风险管理。为此,泛美卫生组织和参与国共同制定了HEARTS质量框架。该模式以区域实施为基础,综合了全球证据和拉丁美洲和加勒比地区的经验教训。它由各国卫生部、保健提供者和国际专家共同设计,将HEARTS战略转化为可操作的系统级目标。明确定义的结果指标和实施目标促进了制度化、质量改进和初级卫生保健的加强,从而支持HEARTS的扩大和公平的结果。《HEARTS质量框架》在适当的情况下,为本区域以外的国家提供了一个切实可行的路线图,以推进基于初级卫生保健的慢性病护理。
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引用次数: 0
The 2025 Lancet Countdown Latin America report: moving from promises to equitable climate action for a prosperous future 2025年《柳叶刀》拉丁美洲倒计时报告:从承诺转向公平的气候行动,实现繁荣的未来
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-12-01 DOI: 10.1016/j.lana.2025.101276
Stella M. Hartinger , Yasna Palmeiro-Silva , Camila Llerena-Cayo , Rayana Santos Araujo Palharini , Christian García-Witulski , Maria Fernanda Salas , Nicolas Valdés-Ortega , Avriel Diaz , Luis E. Escobar , Carolina Gil Posse , Juliana Helo Sarmiento , Andres G. Lescano , Oscar Melo , Mónica Pinilla-Roncancio , David Rojas-Rueda , Tatiana Souza de Camargo , Bruno Takahashi , Luciana Blanco-Villafuerte , Nicolas Borchers-Arriagada , Marcia Chame , Marina Romanello
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引用次数: 0
Urbanicity, parental social deprivation, and risk of early psychosis in Chile: a national cohort study 智利的城市化、父母社会剥夺和早期精神病风险:一项国家队列研究
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-12-01 DOI: 10.1016/j.lana.2025.101282
Franco Mascayano , Javiera Burgos , Viviana Hernandez , Rodrigo Casanueva , Xinyu Yang , Zeyu Li , Param Sampat , Maria Teresa Muñoz-Quezada , Sebastian Rojas-Navarro , Katrina Rodriguez , Jeanette Stingone , Lawrence Yang , Ezra Susser

Background

In Northern Europe, several studies have indicated that people born and raised in urban areas have an increased risk of psychosis. Emerging research in the Global South has produced more heterogeneous and inconsistent findings, suggesting that the impact of urban environments on psychosis risk may depend on social context and broader environmental factors at multiple levels.

Methods

We constructed a cohort of 5,137,561 individuals born in Chile (1992–2012) using the national first episode psychosis (FEP) and Birth and Death registries. We identified 14,410 individuals with nonaffective FEP (ICD-10 F20–F29) recorded between 2005 and 2022. Urbanicity at birth (urban vs rural) was our main exposure. We estimated incidence rate ratios (IRRs) via Poisson regression, adjusting for year of birth and region to account for birth-cohort effects. We also examined whether parental education and employment—two indicators of social deprivation—modified this association.

Findings

Over ∼92 million person-years, the crude incidence rate was 15.67 per 100,000 person-years (95% CI: 15.42, 15.93). No overall association between urbanicity at birth and non-affective FEP was found after accounting for social factors (adjusted IRR = 0.96, 95% CI: 0.91, 1.01). However, parental low education appeared to modify the association between urbanicity and psychosis on both multiplicative and additive scales, with an additive interaction (RERI = 0.33, 95% CI: 0.18, 0.47), supporting a model where urbanicity increases psychosis risk primarily in the presence of social deprivation.

Interpretation

Urban birth alone was not associated with higher FEP incidence in Chile, but an elevated risk was seen among families with lower educational attainment in urban areas. This suggests a causal interplay between urbanicity and social deprivation, underscoring the importance of multilevel frameworks for understanding psychosis risk, especially in rapidly urbanizing societies.

Funding

None.
在北欧,一些研究表明,在城市地区出生和长大的人患精神病的风险更高。新兴研究在全球南方产生了更多的异质和不一致的发现,表明城市环境对精神病风险的影响可能取决于社会背景和更广泛的环境因素在多个层面上。方法:采用国家首发精神病(FEP)和出生与死亡登记,构建了一个5137561名智利出生(1992-2012)的队列。我们确定了2005年至2022年间记录的14,410例非情感性FEP (ICD-10 F20-F29)。出生时的城市化(城市vs农村)是我们的主要暴露点。我们通过泊松回归估计发病率比(IRRs),调整出生年份和地区以考虑出生队列效应。我们还研究了父母教育和就业——社会剥夺的两个指标——是否改变了这种联系。结果:在9200万人年中,粗发病率为15.67 / 10万人年(95% CI: 15.42, 15.93)。考虑到社会因素后,出生时的城市化程度与非情感性FEP之间没有总体关联(调整后的IRR = 0.96, 95% CI: 0.91, 1.01)。然而,父母受教育程度低似乎在乘法和加性尺度上都改变了城市化和精神病之间的关联,具有加性相互作用(ri = 0.33, 95% CI: 0.18, 0.47),支持城市化主要在社会剥夺的情况下增加精神病风险的模型。在智利,仅城市出生与较高的FEP发病率无关,但在城市地区受教育程度较低的家庭中,风险较高。这表明城市化和社会剥夺之间存在因果关系,强调了多层次框架对理解精神病风险的重要性,特别是在快速城市化的社会中。
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引用次数: 0
Socioeconomic disparities and dog rabies: a retrospective analysis of high-spatial-resolution surveillance data from a Latin American city 社会经济差异与犬狂犬病:对拉丁美洲某城市高空间分辨率监测数据的回顾性分析
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-12-01 DOI: 10.1016/j.lana.2025.101285
Sherrie Xie , Julianna Shinnick , Elvis W. Diaz , Edith Zegarra , Ynes Monroy , Sergio E. Recuenco , Ricardo Castillo-Neyra

Background

Dog-mediated human rabies is intuitively linked to poverty, but few studies have formally investigated the relationship between local socioeconomic disadvantage and dog rabies incidence.

Methods

We leveraged a unique, high-spatial-resolution surveillance database from the rabies-endemic city of Arequipa, Peru to probe the relationship between neighbourhood socioeconomic status (SES) and dog rabies risk in 2015–2022. Rabies cases and samples were assigned to the SES level of their block or locality of origin, respectively. We tested the hypothesis that lower SES is associated with increased case positivity and used a spatial statistical model to understand how sample positivity varied spatially.

Findings

Rabies cases were concentrated in socioeconomically disadvantaged blocks (p < 0.001), and sample positivity had a significant and positive association with neighbourhood disadvantage (p < 0.05 for all periods), suggesting that surveillance effort was low relative to case incidence in disadvantaged areas. Stratifying samples by those collected via active vs. passive surveillance revealed that active surveillance reduced disparities in surveillance effort and sample positivity. Spatial analysis identified a sample positivity hotspot in a socioeconomically disadvantaged region with low access to health facilities.

Interpretation

Dog-mediated rabies is known to impact the poorest regions globally. We found similar patterns mirrored on a much smaller spatial scale–within a single city's limits. A balanced approach combining spatially-targeted (“active”) and community-based (“passive”) surveillance can help reduce rabies disparities. Mass dog vaccination and surveillance programs could target disadvantaged neighbourhoods to allocate resources to the most impacted areas and more effectively control dog rabies epidemics.

Funding

US National Institutes of Health.
狗介导的人类狂犬病直观地与贫困有关,但很少有研究正式调查当地社会经济劣势与犬狂犬病发病率之间的关系。方法利用来自秘鲁阿雷基帕狂犬病流行城市的独特的高空间分辨率监测数据库,探讨2015-2022年社区社会经济地位(SES)与犬狂犬病风险的关系。狂犬病病例和样本分别被分配到其所在街区或原产地区的SES水平。我们检验了低SES与病例阳性增加相关的假设,并使用空间统计模型来了解样本阳性如何在空间上变化。发现狂犬病病例集中在社会经济条件较差的街区(p < 0.001),样本阳性与社区条件差呈显著正相关(所有时期p <; 0.05),表明相对于条件差地区的病例发生率,监测力度较低。通过主动和被动监测收集的样本进行分层,发现主动监测减少了监测努力和样本阳性的差异。空间分析确定了一个社会经济条件较差、卫生设施可及性较低的地区的样本阳性热点。众所周知,狗介导的狂犬病会影响全球最贫穷的地区。我们发现类似的模式反映在更小的空间尺度上——在单个城市的范围内。结合空间目标(“主动”)和社区(“被动”)监测的平衡方法可以帮助缩小狂犬病的差距。大规模犬类疫苗接种和监测计划可以针对弱势社区,将资源分配给受影响最严重的地区,并更有效地控制犬类狂犬病流行。资助美国国立卫生研究院。
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引用次数: 0
The fine line between the cure and the illness: the risks of prescriptive emotionality and sociality for youth mental health 治疗与疾病之间的界限:规范情绪和社会性对青少年心理健康的风险
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-11-29 DOI: 10.1016/j.lana.2025.101310
Aurélie Montagne , Cécile Rousseau , Ana Gómez-Carrillo
School-based initiatives are increasingly promoted as solutions to the youth mental health crisis, with Social Emotional Learning (SEL) among the most widely adopted frameworks worldwide. While designed to foster healthy socio-emotional development, evidence for SEL’s long-term mental health benefits remains mixed. Concerns are also growing that universal, non-targeted SEL programs may inadvertently pathologize normal developmental experiences, reinforce self-monitoring, or generate cultural mismatches that undermine resilience. In this personal view, we examine key challenges associated with universal (i.e., non-targeted and intended for all students regardless of baseline risk) school-based programs modeled on SEL. While acknowledging their potential to promote youth well-being, we argue that prescriptive approaches to emotions and sociality can foster confusion among families, resistance among youth, and unintended distress. We highlight risks stemming from conceptual ambiguities and variability in implementation. Rather than abandoning universal programs, we call for rigorous evaluation, cultural adaptation, and integration within broader ecosocial-strategies to foster authentic, context-sensitive resilience in youth.
以学校为基础的倡议越来越多地被推广为解决青少年心理健康危机的办法,其中社会情绪学习(SEL)是世界上最广泛采用的框架之一。虽然SEL旨在促进健康的社会情感发展,但其长期心理健康益处的证据仍是喜忧参半。越来越多的人担心,普遍的、无针对性的SEL项目可能会在不经意间使正常的发展经历病态化,加强自我监控,或产生破坏适应力的文化不匹配。在这一个人观点中,我们研究了与基于SEL模型的普遍(即,非针对性的,面向所有学生的,无论基线风险如何)学校项目相关的主要挑战。虽然承认它们促进青少年福祉的潜力,但我们认为,对情感和社交的规定性方法可能会助长家庭之间的混乱,青少年之间的抵抗和意外的痛苦。我们强调了概念的模糊性和实施中的可变性所带来的风险。我们不应放弃普遍计划,而是呼吁在更广泛的生态社会战略中进行严格的评估、文化适应和整合,以培养真正的、对环境敏感的青年复原力。
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引用次数: 0
Head and neck cancer mortality by gender, region and ethnicity: a population-based study in Brazil 按性别、地区和种族划分的头颈癌死亡率:巴西一项基于人群的研究
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-11-29 DOI: 10.1016/j.lana.2025.101306
Matheus de Abreu , Maria do Rosario Dias de Oliveira Latorre , Maria Paula Curado

Background

Brazil exhibits the highest mortality rates for oral cavity (OCC), oropharyngeal (OPC), and laryngeal (LC) cancers in South-America. This study aims to analyze mortality trends in head and neck cancers (HNC) across the Brazilian population over 44-year period.

Methods

A time-series ecological study was conducted using OCC, OPC, LC mortality data. Age-period-cohort (APC) effects and the average annual percent change (AAPC) were estimated for each cancer subsite by gender, regions, ethnicity.

Findings

From 1980 to 2023, 303,882 HNC deaths were recorded among adults ≥40 years. LC predominated (45.4%), followed by OCC (30.5%), OPC (24.1%). Mortality rates were higher in men, LC showing the highest. After 2000, mortality declines for LC (RR: 0.98 [0.98–1.00 CI 95%]) in men, while women increasing mortality for OPC (RR: 1.12 [1.04–1.21]), OCC (RR: 1.08 [1.02–1.15]). Men born after-1955 showed reduced RR for all subsites, women exhibited for LC. The Northeast region showed an increasing trend across all age groups and cancer subsites. OPC presented an increase in mortality in all regions, in contrast to LC and OCC, which declined in the South and Southeast. White men had a decreasing trend for LC (AAPC −1.62 [−1.99 to −1.26]), OCC (AAPC −1.01 [−1.31 to −0.71]), OPC (AAPC −0.60 [−0.98 to −0.24]), whereas Brown showed an increasing for both genders in all subsites.

Interpretation

Gender, ethnicity, and geographic location are associated with HNC mortality in Brazil. White men and developed regions showed the most substantial improvements in mortality, while brown, women, and people in the North/Northeast exhibited concerning increases. OPC, although with the lowest rates, shows a growing mortality trend nationwide.

Funding

CAPES-Brazil.
巴西是南美洲口腔癌(OCC)、口咽癌(OPC)和喉癌(LC)死亡率最高的国家。本研究旨在分析44年来巴西人群头颈癌(HNC)的死亡率趋势。方法采用OCC、OPC、LC死亡率数据进行时序生态学研究。按性别、地区、种族估计每个癌症亚位点的年龄-时期-队列(APC)效应和年均百分比变化(AAPC)。从1980年到2023年,在≥40岁的成年人中记录了303,882例HNC死亡。LC占主导地位(45.4%),其次是OCC (30.5%), OPC(24.1%)。男性死亡率更高,LC最高。2000年后,男性LC的死亡率下降(RR: 0.98 [0.98 - 1.00 CI 95%]),而女性OPC的死亡率上升(RR: 1.12 [1.04-1.21]), OCC (RR: 1.08[1.02-1.15])。1955年以后出生的男性所有亚位点的RR均降低,女性则为LC。东北地区在所有年龄组和癌症亚位点均呈现上升趋势。OPC在所有区域的死亡率均呈上升趋势,而LC和OCC在南部和东南部呈下降趋势。白人男性的LC (AAPC - 1.62[- 1.99 ~ - 1.26])、OCC (AAPC - 1.01[- 1.31 ~ - 0.71])、OPC (AAPC - 0.60[- 0.98 ~ - 0.24])呈下降趋势,而布朗男性在所有亚位中均呈上升趋势。性别、种族和地理位置与巴西HNC死亡率相关。白人男性和发达地区在死亡率方面表现出最显著的改善,而棕色人种、女性和北部/东北部的人则表现出相应的增长。尽管OPC的死亡率最低,但全国范围内的死亡率呈上升趋势。
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引用次数: 0
Dengue virus genetic diversity in unvaccinated and vaccinated dengue-infected individuals: an observational analysis of the Butantan-DV phase 3 trial in Brazil 未接种疫苗和接种疫苗的登革热感染者的登革热病毒遗传多样性:对巴西Butantan-DV 3期试验的观察性分析
IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2025-11-29 DOI: 10.1016/j.lana.2025.101309
Lívia Sacchetto , Beatriz de Carvalho Marques , Cecília Artico Banho , Victoria Bernardi , Cássia Fernanda Estofolete , Cecília Luiza Simões dos Santos , Maria do Carmo Sampaio Tavares Timenetsky , Marcus Vinícius Guimarães de Lacerda , Angela Carvalho Freitas , Dhelio Batista Pereira , Allex Jardim da Fonseca , Ricardo Queiroz Gurgel , Ivo Castelo-Branco Coelho , Cor Jesus Fernandes Fontes , Ernesto Torres de Azevedo Marques Júnior , Gustavo Adolfo Sierra Romero , Mauro Martins Teixeira , André Machado de Siqueira , Viviane Sampaio Boaventura , Fabiano Ramos , Maurício Lacerda Nogueira

Background

Dengue has emerged as a public health challenge in Brazil since the early 1980s, and it is currently one of the most affected regions and an epicenter of the disease. The country faced its worst dengue epidemic on record, with the co-circulation of different dengue virus (DENV) serotypes alongside genotypes and lineages. This scenario stresses the urgent need for a vaccination strategy that addresses the current burden by protecting against all four DENV serotypes and ensuring safety despite a history of dengue exposure, given the high seroprevalence of dengue in Brazil.

Methods

In this study, we analyzed 365 DENV-1 and DENV-2 wild-type positive samples from unvaccinated and vaccinated (28 days post-vaccination) dengue-infected participants enrolled in the Butantan–dengue vaccine (Butantan-DV) phase 3 trial conducted in Brazil from 2016 to 2021. Genome sequences were obtained from 160 samples in order to analyze the genetic diversity of these strains through phylogenetic and genomic studies.

Findings

The 365 participants (mean age: 16.6, range: 2–59; male: 52.3%, female: 47.7%) enrolled and tested positive for DENV-1 and DENV-2 from both groups (vaccinated and placebo) reflected the spatial and epidemic patterns recorded in the country during the study period. Despite the limited statistical power due to the low number of samples, we observed significantly lower RT-qPCR Ct values in the vaccinated group, particularly for the DENV-1 cases, suggesting that the vaccine could be reducing viral replication. Additionally, vaccine breakthrough infections were not linked with any specific DENV-1 or DENV-2 lineage. Genetic diversity analysis showed no differences in intra-host synonymous or non-synonymous mutation rates between the groups, combined with the absence of positive selection sites in the DENV-1 and DENV-2 coding regions.

Interpretation

Our phylogenetic data demonstrate that Butantan-DV breakthrough infections is not linked to any unique DENV-1 or DENV-2 lineages. The circulating strains in both groups reflect typical transmission patterns of both viruses, highlighting instances of co-circulation and lineage replacement. Notably, the absence of positive selection sites and stable synonymous/non-synonymous mutation rates provides suggestive evidence that the vaccine does not promote vaccine-driven adaptive evolution.

Funding

Instituto Butantan, National Institutes of Health, National Council for Science and Technology and Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Instituto Nacional de Ciência e Tecnologia em Dengue (INCT), INCT Viral Genomic Surveillance and One Health, São Paulo Research Foundation.
自20世纪80年代初以来,登革热已成为巴西的一项公共卫生挑战,目前它是受影响最严重的地区之一,也是该疾病的中心。该国面临有记录以来最严重的登革热流行,不同登革热病毒(DENV)血清型与基因型和谱系同时流行。鉴于巴西登革热的高血清流行率,这一情况强调迫切需要制定一项疫苗接种战略,通过预防所有四种登革热血清型并确保在有登革热暴露史的情况下仍然安全,解决目前的负担。方法在本研究中,我们分析了2016年至2021年在巴西进行的butantan -登革热疫苗(Butantan-DV)三期试验中,来自未接种疫苗和接种疫苗(接种后28天)登革热感染参与者的365份DENV-1和DENV-2野生型阳性样本。从160份样品中获得基因组序列,通过系统发育和基因组学研究分析这些菌株的遗传多样性。研究结果:365名参与者(平均年龄:16.6岁,范围:2-59岁;男性:52.3%,女性:47.7%)入组,两组(接种疫苗和安慰剂)的DENV-1和DENV-2检测呈阳性,反映了研究期间该国记录的空间和流行模式。尽管由于样本数量少,统计能力有限,但我们观察到接种疫苗组的RT-qPCR Ct值显着降低,特别是对于DENV-1病例,这表明疫苗可以减少病毒复制。此外,疫苗突破感染与任何特定的DENV-1或DENV-2谱系无关。遗传多样性分析显示,两组间宿主内同义突变率和非同义突变率没有差异,且DENV-1和DENV-2编码区没有阳性选择位点。我们的系统发育数据表明,Butantan-DV突破感染与任何独特的DENV-1或DENV-2谱系无关。两组中流行的毒株反映了两种病毒的典型传播模式,突出了共循环和谱系替换的实例。值得注意的是,缺乏阳性选择位点和稳定的同义/非同义突变率提供了启发性证据,表明该疫苗不会促进疫苗驱动的适应性进化。资助:布坦坦研究所、国家卫生研究院、国家科学技术委员会和米纳斯吉拉斯州安帕罗共和国基金会、Ciência国家登革热技术研究所(INCT)、INCT病毒基因组监测和一种健康、圣保罗研究基金会。
{"title":"Dengue virus genetic diversity in unvaccinated and vaccinated dengue-infected individuals: an observational analysis of the Butantan-DV phase 3 trial in Brazil","authors":"Lívia Sacchetto ,&nbsp;Beatriz de Carvalho Marques ,&nbsp;Cecília Artico Banho ,&nbsp;Victoria Bernardi ,&nbsp;Cássia Fernanda Estofolete ,&nbsp;Cecília Luiza Simões dos Santos ,&nbsp;Maria do Carmo Sampaio Tavares Timenetsky ,&nbsp;Marcus Vinícius Guimarães de Lacerda ,&nbsp;Angela Carvalho Freitas ,&nbsp;Dhelio Batista Pereira ,&nbsp;Allex Jardim da Fonseca ,&nbsp;Ricardo Queiroz Gurgel ,&nbsp;Ivo Castelo-Branco Coelho ,&nbsp;Cor Jesus Fernandes Fontes ,&nbsp;Ernesto Torres de Azevedo Marques Júnior ,&nbsp;Gustavo Adolfo Sierra Romero ,&nbsp;Mauro Martins Teixeira ,&nbsp;André Machado de Siqueira ,&nbsp;Viviane Sampaio Boaventura ,&nbsp;Fabiano Ramos ,&nbsp;Maurício Lacerda Nogueira","doi":"10.1016/j.lana.2025.101309","DOIUrl":"10.1016/j.lana.2025.101309","url":null,"abstract":"<div><h3>Background</h3><div>Dengue has emerged as a public health challenge in Brazil since the early 1980s, and it is currently one of the most affected regions and an epicenter of the disease. The country faced its worst dengue epidemic on record, with the co-circulation of different dengue virus (DENV) serotypes alongside genotypes and lineages. This scenario stresses the urgent need for a vaccination strategy that addresses the current burden by protecting against all four DENV serotypes and ensuring safety despite a history of dengue exposure, given the high seroprevalence of dengue in Brazil.</div></div><div><h3>Methods</h3><div>In this study, we analyzed 365 DENV-1 and DENV-2 wild-type positive samples from unvaccinated and vaccinated (28 days post-vaccination) dengue-infected participants enrolled in the Butantan–dengue vaccine (Butantan-DV) phase 3 trial conducted in Brazil from 2016 to 2021. Genome sequences were obtained from 160 samples in order to analyze the genetic diversity of these strains through phylogenetic and genomic studies.</div></div><div><h3>Findings</h3><div>The 365 participants (mean age: 16.6, range: 2–59; male: 52.3%, female: 47.7%) enrolled and tested positive for DENV-1 and DENV-2 from both groups (vaccinated and placebo) reflected the spatial and epidemic patterns recorded in the country during the study period. Despite the limited statistical power due to the low number of samples, we observed significantly lower RT-qPCR Ct values in the vaccinated group, particularly for the DENV-1 cases, suggesting that the vaccine could be reducing viral replication. Additionally, vaccine breakthrough infections were not linked with any specific DENV-1 or DENV-2 lineage. Genetic diversity analysis showed no differences in intra-host synonymous or non-synonymous mutation rates between the groups, combined with the absence of positive selection sites in the DENV-1 and DENV-2 coding regions.</div></div><div><h3>Interpretation</h3><div>Our phylogenetic data demonstrate that Butantan-DV breakthrough infections is not linked to any unique DENV-1 or DENV-2 lineages. The circulating strains in both groups reflect typical transmission patterns of both viruses, highlighting instances of co-circulation and lineage replacement. Notably, the absence of positive selection sites and stable synonymous/non-synonymous mutation rates provides suggestive evidence that the vaccine does not promote vaccine-driven adaptive evolution.</div></div><div><h3>Funding</h3><div><span>Instituto Butantan</span>, <span>National Institutes of Health</span>, <span>National Council for Science and Technology</span> and <span>Fundação de Amparo à Pesquisa do Estado de Minas Gerais</span>, <span>Instituto Nacional de Ciência e Tecnologia em Dengue</span> (INCT), <span>INCT Viral Genomic Surveillance and One Health</span>, <span>São Paulo Research Foundation</span>.</div></div>","PeriodicalId":29783,"journal":{"name":"Lancet Regional Health-Americas","volume":"53 ","pages":"Article 101309"},"PeriodicalIF":7.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Lancet Regional Health-Americas
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