Publications by authors named "Timothy Endy"

Uncovering rates at which susceptible individuals become infected with a pathogen, i.e., the force of infection (FOI), is essential for assessing transmission risk and reconstructing distribution of immunity in a population.

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Dengue virus (DENV) is an increasingly important human pathogen, with already half of the globe's population living in environments with transmission potential. Since only a minority of cases are captured by direct detection methods (RT-PCR or antigen tests), serological assays play an important role in the diagnostic process. However, individual assays can suffer from low sensitivity and specificity and interpreting results from multiple assays remains challenging, particularly because interpretations from multiple assays may differ, creating uncertainty over how to generate finalized interpretations.

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Uncovering rates at which susceptible individuals become infected with a pathogen, i.e. the force of infection (FOI), is essential for assessing transmission risk and reconstructing distribution of immunity in a population.

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Article Synopsis
  • * Despite their importance, current RDTs suffer from limitations in clinical sensitivity and specificity, require significant funding for development, and struggle with implementation, especially in low-income countries due to insufficient investments and competing health priorities.
  • * The recent World Health Assembly resolution highlights the need for enhanced diagnostic capabilities, but it lacks binding power, making it crucial to seek funding mechanisms like the Pandemic Fund to improve RDT development for better pandemic preparedness.
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Article Synopsis
  • - The study evaluated the safety and immune response of a low-dose DENV-3 challenge model in nine healthy individuals, following subcutaneous inoculation with an attenuated dengue virus strain.
  • - All participants developed detectable viral RNA within a week, with symptoms like fever, rash, and laboratory abnormalities indicating mild-to-moderate dengue.
  • - Immunological responses, including seroconversion and memory T cell activation, were evident within 14 days, and the severity of clinical symptoms correlated with the peak viral load in each participant.
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Although it is known that household infections drive the transmission of dengue virus (DENV), it is unclear how household composition and the immune status of inhabitants affect the individual risk of infection. Most population-based studies to date have focused on paediatric cohorts because more severe forms of dengue mainly occur in children, and the role of adults in dengue transmission is understudied. Here we analysed data from a multigenerational cohort study of 470 households, comprising 2,860 individuals, in Kamphaeng Phet, Thailand, to evaluate risk factors for DENV infection.

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Infants less than 1 y of age experience high rates of dengue disease in dengue virus (DENV) endemic countries. This burden is commonly attributed to antibody-dependent enhancement (ADE), whereby concentrations of maternally derived DENV antibodies become subneutralizing, and infection-enhancing. Understanding antibody-related mechanisms of enhanced infant dengue disease risk represents a significant challenge due to the dynamic nature of antibodies and their imperfect measurement processes.

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Chikungunya is an arboviral disease caused by the chikungunya virus (CHIKV) afflicting tropical and sub-tropical countries worldwide. It has been identified as a priority pathogen by the Coalition for Epidemics Preparedness Innovations (CEPI) and as an emerging infectious disease (EID) necessitating further action as soon as possible by the World Health Organization (WHO). Recent studies suggest that disability-adjusted life years (DALYs) due to CHIKV infection are as high as 106,089 DALYs lost globally.

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Soil-transmitted helminth infections are assumed to be uncommon in the US, despite numerous studies in the past few decades showing high burdens in Appalachia and the southern states. We assessed trends of interest in the Google search engine to gauge spatiotemporal patterns of potential soil-transmitted helminth transmission. We conducted a further ecological study comparing Google search trends to risk factors for soil-transmitted helminth transmission.

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Introduction: Dengue is a worsening global public health problem. The vector-viral-host interactions driving the pathogenesis of dengue are multi-dimensional. Sequential dengue virus (DENV) infections with different DENV types significantly increase the risk of severe disease.

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Article Synopsis
  • - Dengue virus (DENV) infections, prevalent in tropical areas, lead to significant health issues, with over 400 million infections annually and around 20,000 deaths, underscoring the need for better understanding of immune responses during infection.
  • - A study was conducted on individuals infected with the DENV-1 strain 45AZ5, revealing a strong immune response characterized by distinct antibodies (IgA, IgM, IgG) and specific delays in antibody production, providing insights into the timing and nature of the body's response.
  • - The research utilized RNA sequencing to identify key gene expression patterns that correlate with the onset of virus replication and adaptive immunity, highlighting important immunological features of primary DENV-1 infections that could
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MIRM is an uncommon entity characterized by prominent mucositis, usually with sparse cutaneous involvement. The diagnosis of MIRM can be challenging due to the lack of awareness amongst clinicians. Patients with Behçet's disease usually present with recurrent and painful mucocutaneous ulcers, while other clinical manifestations of the disease are more variable.

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The mean age of dengue hemorrhagic fever (DHF) cases increased considerably in Thailand from 8.1 to 24.3 y between 1981 and 2017 (mean annual increase of 0.

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Background: Dengue virus (DENV) often circulates endemically. In such settings with high levels of transmission, it remains unclear whether there are risk factors that alter individual infection risk.

Methods: We tested blood taken from individuals living in multigenerational households in Kamphaeng Phet province, Thailand for DENV antibodies (N = 2364, mean age 31 years).

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Conventional methods for quantifying and phenotyping antigen-specific lymphocytes can rapidly deplete irreplaceable specimens. This is due to the fact that antigen-specific T and B cells have historically been analyzed in independent assays each requiring millions of cells. A technique that facilitates the simultaneous detection of antigen-specific T and B cells would allow for more thorough immune profiling with significantly reduced sample requirements.

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Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity. One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of F gamma receptor-bearing cells.

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Individual houses with high risks of dengue virus (DENV) transmission might be a source of virus transmission within the neighborhood. We conducted an entomological risk assessment for DENV transmission at the household level, comprising family cohort members residing in the same location, to assess the risk for dengue virus transmitted by mosquito vectors. The studies were conducted in Kamphaeng Phet Province, Thailand, during 2016-2020.

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Memory T cells resulting from primary dengue virus (DENV) infection are hypothesized to influence the clinical outcome of subsequent DENV infection. However, the few studies involving prospectively collected blood samples have found weak and inconsistent associations with outcome and variable temporal trends in DENV-specific memory T cell responses between subjects. This study used both and cultured ELISPOT assays to further evaluate the associations between DENV serotype-cross-reactive memory T cells and severity of secondary infection.

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In the latest World Health Organization (WHO) recommendation for Dengvaxia implementation, either serological testing or a person's history of prior dengue illness may be used as supporting evidence to identify dengue virus (DENV)-immune individuals eligible for vaccination, in areas with limited capacity for laboratory confirmation. This analysis aimed to estimate the concordance between self-reported dengue illness histories and seropositivity in a prospective cohort study for dengue virus infection in Kamphaeng Phet province, a dengue-endemic area in northern Thailand. The study enrolled 2,076 subjects from 516 multigenerational families, with a median age of 30.

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Hepatitis E (HE) during pregnancy can be fatal; there are no prospective risk estimates for HE and its complications during pregnancy. We followed 2,404 pregnant women for HE and pregnancy outcomes from 1996 to 1998. Subjects from Nepal were enrolled at an antenatal clinic with pregnancy of ≤ 24 weeks.

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SARS-CoV-2 represents an unprecedented public health challenge. While the majority of SARS-CoV-2-infected individuals with mild-to-moderate COVID-19 resolve their infection with few complications, some individuals experience prolonged symptoms lasting for weeks after initial diagnosis. Persistent viral infections are commonly accompanied by immunologic dysregulation, but it is unclear if persistent COVID-19 impacts the development of virus-specific cellular immunity.

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Dengue control approaches are best informed by granular spatial epidemiology of these viruses, yet reconstruction of inter- and intra-household transmissions is limited when analyzing case count, serologic, or genomic consensus sequence data. To determine viral spread on a finer spatial scale, we extended phylogenomic discrete trait analyses to reconstructions of house-to-house transmissions within a prospective cluster study in Kamphaeng Phet, Thailand. For additional resolution and transmission confirmation, we mapped dengue intra-host single nucleotide variants on the taxa of these time-scaled phylogenies.

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Background: Soil transmitted helminths (STH) are a common infection among pregnant women in areas with poor access to sanitation. Deworming medications are cheap and safe; however, the health benefit of deworming during pregnancy is not clear.

Methods / Principal Findings: We created a retrospective cohort of more than 800,000 births from 95 Demographic and Health Survey datasets to estimate the impact of deworming medicine during routine antenatal care (ANC) on neonatal mortality and low birthweight.

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The management of mosquito-borne diseases is a challenge in southern coastal Ecuador, where dengue is hyper-endemic and co-circulates with other arboviral diseases. Prior work in the region has explored social-ecological factors, dengue case data, and entomological indices. In this study, we bring together entomological and epidemiological data to describe links between social-ecological factors associated with risk of dengue transmission at the household level in Machala, Ecuador.

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Dengue human infection studies present an opportunity to address many longstanding questions in the field of flavivirus biology. However, limited data are available on how the immunological and transcriptional response elicited by an attenuated challenge virus compares to that associated with a wild-type DENV infection. To determine the kinetic transcriptional signature associated with experimental primary DENV-1 infection and to assess how closely this profile correlates with the transcriptional signature accompanying natural primary DENV-1 infection, we utilized scRNAseq to analyze PBMC from individuals enrolled in a DENV-1 human challenge study and from individuals experiencing a natural primary DENV-1 infection.

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