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Dengue, caused by four closely related viruses, is a growing global public health concern, with outbreaks capable of overwhelming health-care systems and disrupting economies. Dengue is endemic in more than 100 countries across tropical and subtropical regions worldwide, and the expanding range of the mosquito vector, affected in part by climate change, increases risk in new areas such as Spain, Portugal, and the southern USA, while emerging evidence points to silent epidemics in Africa. Substantial advances in our understanding of the virus, immune responses, and disease progression have been made within the past decade. Novel interventions have emerged, including partially effective vaccines and innovative mosquito control strategies, although a reliable immune correlate of protection remains a challenge for the assessment of vaccines. These developments mark the beginning of a new era in dengue prevention and control, offering promise in addressing this pressing global health issue.
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Aedes , Virus del Dengue , Dengue , Vacunas , Animales , Humanos , Dengue/epidemiología , Dengue/prevención & control , Brotes de Enfermedades/prevención & control , Salud PúblicaRESUMEN
Vaccine herd protection is the extension of the defense conferred by immunization beyond the vaccinated to unvaccinated persons in a population, as well as the enhancement of the protection among the vaccinated, due to vaccination of the surrounding population. Vaccine herd protection has traditionally been inferred from observations of disease trends after inclusion of a vaccine in national immunization schedules. Rather than awaiting outcomes of widescale vaccine deployment, earlier-stage evaluation of vaccine herd protection during trials or mass vaccination projects could help inform policy decisions about potential vaccine introduction. We describe the components, influencing factors, and implications of vaccine herd protection and discuss various methods for assessing herd protection, using examples from cholera and typhoid vaccine studies.
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Vacunas contra el Cólera/administración & dosificación , Cólera/prevención & control , Inmunidad Colectiva , Fiebre Tifoidea/prevención & control , Vacunas Tifoides-Paratifoides/administración & dosificación , Administración Oral , Humanos , Vacunación , Eficacia de las VacunasRESUMEN
Zika virus (ZIKV) is a member of the Flaviviridae family, which includes other clinically notable viruses such as the 4 dengue virus serotypes (DENV-1-4). Distinguishing DENVs from ZIKV using the established serologic assays widely used for monitoring DENV transmission is difficult because of antibody cross-reactivity between these closely related flaviviruses. We describe a modified and improved recombinant envelope domain III-based serologic assay for detecting ZIKV type-specific antibodies in regions with endemic DENV transmission. When the assay was used to measure ZIKV seroprevalence in 2017 among children 9-14 years of age living in a region of the Philippines with endemic DENV transmission, we observed a ZIKV seroprevalence of 18%. Investigators should consider using the ZIKV envelope domain III-based assay, which is simple and readily adaptable for use in standard clinical and public health laboratories, to assess ZIKV seroprevalence in areas with endemic DENV transmission.
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Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Anticuerpos Antivirales , Niño , Reacciones Cruzadas , Dengue/diagnóstico , Dengue/epidemiología , Virus del Dengue/genética , Humanos , Filipinas/epidemiología , Estudios Seroepidemiológicos , Virus Zika/genética , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiologíaRESUMEN
BACKGROUND: Reactive malaria case detection involves the screening of those in contact with index cases and is used in countries in the Greater Mekong Sub-region. The yield of reactive case detection, defined here as the percentage of positive malaria cases among potential contacts who were screened, was assessed. METHODS: A literature search was conducted on PubMed to identify studies on reactive case detection in the Greater Mekong Sub-region. Eligible published articles were reviewed and pooled estimates from the studies were calculated, by type of malaria test used. RESULTS: Eighty-five publications were retrieved, of which 8 (9.4%) eligible articles were included in the analysis. The yield from reactive case detection ranged from 0.1 to 4.2%, with higher rates from PCR testing compared with microscopy and/or rapid diagnostic test. The overall yield from microscopy and/or rapid diagnostic test was 0.56% (95% CI 0.31-0.88%), while that from PCR was 2.35% (95% CI 1.19-3.87%). The two studies comparing different target groups showed higher yield from co-workers/co-travellers, compared with household contacts. CONCLUSION: In low malaria transmission settings, the effectiveness of reactive case detection is diminishing. In the Greater Mekong Sub-region, modifying reactive case detection from household contacts to co-workers/co-travellers and from testing to presumptive treatment of targeted contacts, could increase the impact of this approach.
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Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Malaria/diagnóstico , Tamizaje Masivo/estadística & datos numéricos , Microscopía/estadística & datos numéricos , Reacción en Cadena de la Polimerasa/estadística & datos numéricos , Asia Sudoriental , HumanosRESUMEN
COVID-19 spreads via aerosols, droplets, fomites and faeces. The built environment that facilitates crowding increases exposure and hence transmission of COVID-19 as evidenced by outbreaks in both cool-dry and hot-humid climates, such as in the US prison system and dormitories in Singapore, respectively. This paper explores how the built environment influences crowding and COVID-19 transmission, focusing on informal urban settlements (slums). We propose policy and practice changes that could reduce COVID-19 transmission. There are several issues on how COVID-19 affects informal urban settlements. Slum populations tend to be younger than the overall population. Lower numbers of older people lessen the morbidity and mortality of the pandemic in slum areas. Second, many slum populations are highly mobile. By returning to their ancestral villages residents can avoid the risks of overcrowding and reduce the population density in a given area but may spread COVID-19 to other areas. Third, detection and registration of COVID-19 cases depends on patients presenting to health care providers. If the risk of visiting a health care centre outweighs the potential benefits patients may prefer not to seek treatment. The control and prevention of COVID-19 in informal urban settlements starts with organizing community infrastructure for diagnosis and treatment and assuring that basic needs (food, water, sanitation, health care and public transport) are met during quarantine. Next, community members at highest risk need to be identified and protected. Low-income, informal settlements need to be recognized as a reservoir and source for persistent transmission. Solutions to overcrowding must be developed for this and future pandemics. In view of the constant risk that slums present to the entire population decisive steps need to be taken to rehabilitate and improve informal settlements, while avoiding stigmatization.
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OBJECTIVE: In many countries, housing is used for wealth accumulation and provides financial security in old age. We tested the hypothesis that household wealth, measured by housing quality and ownership of durable assets, would increase with age of the household head. METHODS: We conducted a survey of household heads in 68 villages surrounding Mtwara town, Tanzania and recorded relevant demographic, housing and social characteristics for each household. The primary analysis assessed the relationship between age of the household head, quality of the house structure and socio-economic score (SES) using multivariate analysis. Principal Components Analysis (PCA) was used as a data reduction tool to estimate the social-economic status of subjects based on relevant variables that are considered as proxy for SES. RESULTS: Of 13 250 household heads were surveyed of whom 49% were male. Those at least 50 years old were more likely to live in homes with an earth floor (86%) compared to younger household heads (80%; P < 0.0001), wattle and daub walls (94% vs. 90%; P < 0.0001) and corrugated iron roofs (56% vs. 52%; P < 0.0001). Wealth accumulation in the villages included in the study tends to be an inverted V-relationship with age. Housing quality and SES rose to a peak by 50 years and then rapidly decreased. Households with a large number of members were more likely to have better housing than smaller households. CONCLUSIONS: Housing plays a critical role in wealth accumulation and socio-economic status of a household in rural villages in Tanzania. Households with a head under 50 years were more likely to live in improved housing and enjoyed a higher SES, than households with older heads. Larger families may provide protection against old age poverty in rural areas. Assuring financial security in old age, specifically robust and appropriate housing would have wide-ranging benefits.
OBJECTIF: Dans de nombreux pays, le logement est utilisé pour l'accumulation de richesse et offre une sécurité financière à un âge avancé. Nous avons testé l'hypothèse selon laquelle la richesse des ménages, mesurée par la qualité du logement et la possession d'actifs durables, augmenterait avec l'âge du chef de ménage. MÉTHODES: Nous avons mené une enquête auprès des chefs de ménage dans 68 villages entourant la ville de Mtwara, en Tanzanie et enregistré les caractéristiques démographiques, de logement et sociales pertinentes pour chaque ménage. L'analyse primaire a évalué la relation entre l'âge du chef de ménage, la qualité de la structure du logement et le score socioéconomique (SES) à l'aide d'une analyse multivariée. L'analyse en composantes principales (ACP) a été utilisée comme outil de réduction des données pour estimer le statut socioéconomique des sujets sur la base de variables pertinentes qui sont considérées comme une approximation du SSE. RÉSULTATS: 13.250 chefs de ménage ont été interrogés, dont 49% de sexe masculin. Les personnes âgées d'au moins 50 ans étaient plus susceptibles de vivre dans des maisons avec un sol en terre (86%) que les chefs de ménage plus jeunes (80%; P < 0,0001), des murs en clayonnage enduit de torchis (94% contre 90%; P < 0,0001) et des toitures en tôle ondulée (56% contre 52%; P < 0,0001). L'accumulation de richesse dans les villages inclus dans l'étude a tendance à être une relation en V inversée avec l'âge. La qualité du logement et le SSE ont atteint un sommet de 50 ans, puis ont rapidement diminué. Les ménages comptant un grand nombre de membres étaient plus susceptibles d'avoir un meilleur logement que les ménages plus petits. CONCLUSIONS: Le logement joue un rôle essentiel dans l'accumulation de richesse et le statut socioéconomique d'un ménage dans les villages ruraux de Tanzanie. Les ménages dont le chef avait moins de 50 ans étaient plus susceptibles de vivre dans un logement amélioré et jouissaient d'un SSE plus élevé que les ménages dont le chef était plus âgé. Les familles plus nombreuses pourraient offrir une protection contre la pauvreté aux personnes âgées dans les zones rurales. Assurer la sécurité financière dans la vieillesse, en particulier un logement solide et approprié, aurait des avantages considérables.
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Envejecimiento , Composición Familiar , Vivienda/estadística & datos numéricos , Relaciones Intergeneracionales , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Población Rural , Factores Socioeconómicos , TanzaníaRESUMEN
Lorenz von Seidlein and colleagues discuss improving house designs in rural Africa to benefit health.
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Arquitectura y Construcción de Instituciones de Salud/métodos , Conocimientos, Actitudes y Práctica en Salud , Vivienda , Malaria/prevención & control , Dinámica Poblacional , Salud Rural , África/epidemiología , Clima , Arquitectura y Construcción de Instituciones de Salud/economía , Promoción de la Salud , Humanos , Humedad , Pobreza , Población RuralRESUMEN
Calciphylaxis is a rare but life-threatening condition, most commonly affecting patients with stage 4 or 5 chronic kidney disease. No universally accepted therapy exists so far. In an attempt to avoid surgical intervention with parathyroidectomy, which is of questionable efficacy and carries several risks, a number of noninvasive treatments have been trialled with variable success. These treatments are aimed at modifying risk factors for calciphylaxis, in particular hypercalcaemia, hyperphosphataemia and hyperparathyroidism. The aim of this review was to summarise the available evidence to determine the potential role of cinacalcet in the treatment of calciphylaxis in patients with chronic kidney disease. Demographic, clinical and laboratory data were retrospectively collected from the available English and non-English literature. Overall, there was a very high response rate (partial or complete) of calciphylaxis lesions to both cinacalcet monotherapy and cinacalcet as part of a combination therapy (83.4% and 82.8%, respectively). When examining complete response to treatment specifically, combination therapy with cinacalcet proved more efficacious than monotherapy (62.1% versus 41.7%). There was also an associated rapid reduction of intact parathyroid hormone over a period of 2-33 months in both groups. While there are limitations as to how our data can be interpreted due to the heterogeneity of the methods and follow-up of the included case reports and case series, prompt and consistent therapy including cinacalcet may help improve the disease outcome. Additional research needs to be performed in this area, to further define the optimal use of cinacalcet for the treatment of calciphylaxis.
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Calcifilaxia/tratamiento farmacológico , Hormonas y Agentes Reguladores de Calcio/uso terapéutico , Cinacalcet/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Terapia Combinada , HumanosRESUMEN
Background: Cholera poses a public health and economic threat to Zanzibar. Detailed epidemiologic analyses are needed to inform a multisectoral cholera elimination plan currently under development. Methods: We collated passive surveillance data from 1997 to 2017 and calculated the outbreak-specific and cumulative incidence of suspected cholera per shehia (neighborhood). We explored the variability in shehia-specific relative cholera risk and explored the predictive power of targeting intervention at shehias based on historical incidence. Using flexible regression models, we estimated cholera's seasonality and the relationship between rainfall and cholera transmission. Results: From 1997 and 2017, 11921 suspected cholera cases were reported across 87% of Zanzibar's shehias, representing an average incidence rate of 4.4 per 10000/year. The geographic distribution of cases across outbreaks was variable, although a number of high-burden areas were identified. Outbreaks were highly seasonal with 2 high-risk periods corresponding to the annual rainy seasons. Conclusions: Shehia-targeted interventions should be complemented with island-wide cholera prevention activities given the spatial variability in cholera risk from outbreak to outbreak. In-depth risk factor analyses should be conducted in the high-burden shehias. The seasonal nature of cholera provides annual windows of opportunity for cholera preparedness activities.
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Cólera/epidemiología , Brotes de Enfermedades/prevención & control , Humanos , Incidencia , Salud Pública , Lluvia , Estaciones del Año , Tanzanía/epidemiologíaRESUMEN
In addition to improved water supply and sanitation, the 2-dose killed oral cholera vaccine (OCV) is an important tool for the prevention and control of cholera. We aimed to document the immunogenicity and protection (efficacy and effectiveness) conferred by a single OCV dose against cholera. The metaanalysis showed that an estimated 73% and 77% of individuals seroconverted to the Ogawa and Inaba serotypes, respectively, after an OCV first dose. The estimates of single-dose vaccine protection from available studies are 87% at 2 months decreasing to 33% at 2 years. Current immunologic and clinical data suggest that protection conferred by a single dose of killed OCV may be sufficient to reduce short-term risk in outbreaks or other high-risk settings, which may be especially useful when vaccine supply is limited. However, until more data suggest otherwise, a second dose should be given as soon as circumstances allow to ensure robust protection.
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Vacunas contra el Cólera/inmunología , Cólera/prevención & control , Inmunogenicidad Vacunal , Vacunas de Productos Inactivados/inmunología , Administración Oral , Vacunas contra el Cólera/administración & dosificación , Brotes de Enfermedades/prevención & control , Humanos , Esquemas de Inmunización , Seroconversión , Serogrupo , Vacunación/métodos , Potencia de la Vacuna , Vacunas de Productos Inactivados/administración & dosificación , Vibrio cholerae/inmunologíaRESUMEN
In a Perspective, Lorenz von Seidlein and Jacqueline L. Deen discuss the implications of Andrew Azman and colleagues' accompanying study for management of cholera outbreaks.
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Vacunas contra el Cólera/uso terapéutico , Cólera/prevención & control , Brotes de Enfermedades/prevención & control , Intervención Médica Temprana/métodos , Necesidades y Demandas de Servicios de Salud , Cólera/epidemiología , Implementación de Plan de Salud/organización & administración , Implementación de Plan de Salud/normas , Necesidades y Demandas de Servicios de Salud/organización & administración , Necesidades y Demandas de Servicios de Salud/normas , Humanos , Medicina Preventiva/métodos , Medicina Preventiva/organización & administración , Administración en Salud Pública/métodos , Administración en Salud Pública/normasRESUMEN
Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a histopathological diagnosis, characterized by a pattern of granulomatosis, which may be associated with leukocytoclastic vasculitis. PNGD most commonly occurs in association with systemic inflammatory disorders, typically autoimmune conditions, such as rheumatoid arthritis and systemic lupus erythromatosus. There are very rare reports of PNGD in patients with lymphoma. We report the case of a 53-year-old female with an erythematous, papular eruption occurring in association with Hodgkin lymphoma. Histopathological evaluation of the rash confirmed PNGD. To the best of our knowledge, this is the first case of PNGD occurring in association with Hodgkin lymphoma. Although extremely rare, underlying malignancy should be considered in patients with PNGD, particularly in individuals with constitutional symptoms and the absence of an obvious inflammatory etiology.
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Dermatitis/etiología , Granuloma/etiología , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/patología , Femenino , Humanos , Persona de Mediana Edad , Infiltración NeutrófilaRESUMEN
In a Perspective, Jacqueline Deeen discusses challenges in balancing the individual and population risks and benefits for CYD-TDV (Dengvaxia), the first available dengue vaccine.
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Vacunas contra el Dengue/normas , Dengue/prevención & control , Vacunación , Vacunas contra el Dengue/efectos adversos , Humanos , Medición de Riesgo , Vacunación/normas , Vacunación/estadística & datos numéricosRESUMEN
OBJECTIVE: To describe and analyse the characteristics of oral cholera vaccination campaigns; including location, target population, logistics, vaccine coverage and delivery costs. METHODS: We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts in the field and in ministries of health and did targeted web searches. FINDINGS: A total of 33 documents were included in the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11-3.99 United States dollars. CONCLUSION: Experience with oral cholera vaccination campaigns continues to increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently.
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Vacunas contra el Cólera/administración & dosificación , Cólera/prevención & control , Programas de Inmunización , Administración Oral , Vacunas contra el Cólera/economía , Salud Global , Humanos , Programas de Inmunización/economía , Práctica de Salud Pública , Vietnam , Organización Mundial de la SaludRESUMEN
The aim of this study was to estimate the economic burden of typhoid fever in Pemba, Zanzibar, East Africa. This study was an incidence-based cost-of-illness analysis from a societal perspective. It covered new episodes of blood culture-confirmed typhoid fever in patients presenting at the outpatient or inpatient departments of three district hospitals between May 2010 and December 2010. Cost of illness was the sum of direct costs and costs for productivity loss. Direct costs covered treatment, travel, and meals. Productivity costs were loss of income by patients and caregivers. The analysis included 17 episodes. The mean age of the patients, was 23 years (range=5-65, median=22). Thirty-five percent were inpatients, with a mean of 4.75 days of hospital stay (range=3-7, median=4.50). The mean cost for treatment alone during hospital care was US$ 21.97 at 2010 prices (US$ 1=1,430.50 Tanzanian ShillingâTSH). The average societal cost was US$ 154.47 per typhoid episode. The major expenditure was productivity cost due to lost wages of US$ 128.02 (83%). Our results contribute to the further economic evaluation of typhoid fever vaccination in Zanzibar and other sub-Saharan African countries.
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Costo de Enfermedad , Eficiencia Organizacional/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Fiebre Tifoidea/economía , Adolescente , Adulto , África del Sur del Sahara/epidemiología , Anciano , Niño , Preescolar , Femenino , Hospitales de Distrito , Humanos , Incidencia , Islas del Oceano Índico/epidemiología , Masculino , Persona de Mediana Edad , Tanzanía/epidemiología , Fiebre Tifoidea/epidemiología , Adulto JovenRESUMEN
The 21st century saw a shift in the cholera burden from Asia to Africa. The risk factors for cholera outbreaks in Africa are incompletely understood, and the traditional emphasis on providing safe drinking water and improving sanitation and hygiene has proven remarkably insufficient to contain outbreaks. Current killed whole-cell oral cholera vaccines (OCVs) are safe and guarantee a high level of protection for several years. OCVs have been licensed for >20 years, but their potential for preventing and control cholera outbreaks in Africa has not been realized. Although each item in the long list of technical reasons why cholera vaccination campaigns have been deferred is plausible, we believe that the biggest barrier is that populations affected by cholera outbreaks are underprivileged and lack a strong political voice. The evaluation and use of OCVs as a tool for cholera control will require a new, more compassionate, less risk-averse generation of decision makers.
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Vacunas contra el Cólera/inmunología , Cólera/epidemiología , Cólera/prevención & control , África/epidemiología , Cólera/economía , Vacunas contra el Cólera/economía , Vacunas contra el Cólera/provisión & distribución , Análisis Costo-Beneficio , Enfermedades Endémicas/prevención & control , Epidemias/prevención & control , Humanos , Vacunación Masiva/economía , Vacunación Masiva/métodos , Ingeniería Sanitaria , Reserva Estratégica/economía , Abastecimiento de AguaRESUMEN
Inactivated oral cholera vaccines (OCVs) are a cornerstone of international efforts to control cholera, and are currently deployed from a global stockpile for the control of epidemics and endemic hotspots, as well as for humanitarian emergencies. One inactivated OCV (with tradenames Shanchol™ and Euvichol-Plus™) is used in the stockpile, but the number of available doses is inadequate to meet the rapidly rising demand for OCVs from countries affected by cholera. Newer, simplified inactivated OCVs under development offer the possibilities of lower expense and higher production yields, and could expand the stockpile. However, their clinical development is made complex because placebo-controlled randomised trials of OCV efficacy are no longer ethically permissible and because the serum vibriocidal antibodies used to measure OCV responses are not correlates of OCV protection against cholera. Here, we propose an observational study design with features to enhance methodological rigor to provide credible evidence of protection against cholera by these newer vaccines.
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BACKGROUND: Care seeking was assessed in preparation for a study of the health impact of novel design houses in rural Mtwara, Tanzania. METHODS: A total of 578 residents of 60 villages participated in this mixed-methods study from April to August 2020. Among them, 550 participated in a healthcare-seeking survey, 17 in in-depth interviews and 28 in key informant interviews. RESULTS: The decision to seek care was based on symptom severity (95.4% [370]). Caregivers first visited non-allopathic healthcare providers or were treated at home, which led to delays in seeking care at healthcare facilities. More than one-third (36.0% [140]) of respondents took >12 h seeking care at healthcare facilities. The majority (73.0% [282]) visited healthcare facilities, whereas around one-fifth (21.0% [80]) sought care at drug stores. Treatment costs deterred respondents from visiting healthcare facilities (61.4% [338]). Only 10 (3.6%) of the households surveyed reported that they were covered by health insurance. CONCLUSIONS: Quality of care, related to institutional factors, impacts timely care seeking for childhood illnesses in Mtwara, Tanzania. Ensuring accessibility of facilities is therefore not sufficient.
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Aceptación de la Atención de Salud , Población Rural , Humanos , Tanzanía , Aceptación de la Atención de Salud/estadística & datos numéricos , Masculino , Femenino , Adulto , Niño , Preescolar , Adolescente , Lactante , Persona de Mediana Edad , Adulto Joven , Accesibilidad a los Servicios de Salud , Instituciones de Salud/estadística & datos numéricos , CuidadoresRESUMEN
Recent work demonstrates the limitations of the standard dengue virus (DENV) neutralization assay to predict protection against dengue. We perform studies to compare how a commercial IgG ELISA, envelope domain III (EDIII) or non-structural protein 1 (NS1) binding antibodies, and titers from plaque reduction neutralization tests (PRNTs) using reference standard and clinical mature viruses are associated with dengue disease. Healthy children (n = 1,206) in Cebu, Philippines were followed for 5 years. High ELISA values (≥3) were associated with reduced dengue probability relative to naïve children (3% vs. 10%, p = 0.008), but antibody binding EDIII or NS1 from each serotype had no association. High standard and mature geometric mean PRNT titers were associated with reduced dengue disease overall (p < 0.01), and high DENV2 and DENV3 titers in both assays provided protection against the matched serotype (p < 0.02). However, while 52% of dengue cases had standard virus PRNT titers > 100, only 2% of cases had mature virus PRNT titers > 100 (p < 0.001), indicating a lower, more consistent threshold for protection. Each assay may be useful for different purposes as correlates of protection in population and vaccine trials.
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Cross-reactive antibodies (Abs) to epitopes that span envelope proteins on the virion surface are hypothesized to protect against dengue. Here, we measured Abs targeting the quaternary envelope dimer epitope (EDE) as well as neutralizing and binding Abs and evaluate their association with dengue virus (DENV) infection, vaccine response, and disease outcome in dengue vaccinated and unvaccinated children (n=252) within a longitudinal cohort in Cebu, Philippines (n=2,996). Abs targeting EDE were prevalent and strongly associated with broad neutralization of DENV1-4 in those with baseline multitypic immunity. Subsequent natural infection and vaccination boosted EDE-like, neutralizing, and binding Abs. EDE-like Abs were associated with reduced dengue risk and mediated the protective effect of binding and neutralizing Abs on symptomatic and severe dengue. Thus, Abs targeting quaternary epitopes help explain broad cross protection in those with multiple prior DENV exposures, making them useful for evaluation and development of future vaccines and therapeutics.