Nowadays there are efforts to contact infection histories with fewer assumptions and in a far more data-driven way, accounting for potential homotypic infections [66,67] as well as for increases [50,68] that usually do not reach the 4-fold rise antibody titer requirement of inapparent infections. predictors of persistent disease [1], cohort research are essential for understanding infectious diseases also. In this research style, individual-level baseline features are assessed in a wholesome inhabitants followed as time passes as participants normally acquire disease, hence enabling id of factors connected with or defensive against disease risk. For instance, two key results of such research include id of distinct transmitting prices of influenza A and B infections among human beings [2] and differential gender-based HIV transmitting rates in discordant couples [3]. Prospective community-, school-, and household-based cohort studies are particularly useful to study acute viral diseases such as dengue. Dengue virus is comprised of four serotypes, DENV1C4. Infection with one serotype provides long-term protection against disease upon re-infection with the same serotype. However, prior immunity can protect against or enhance disease during secondary heterotypic DENV infection, which is the greatest risk factor for severe dengue, Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS). DHF/DSS is thought to be caused in part by antibody-dependent enhancement (ADE): sub-neutralizing antibody titers enhance viremia [4] by enabling infection of monocytes and macrophages via Fc receptors [5,6]; this instigates pathologic immune cell activation and elevated NS1 secretion that result in vascular leak and shock [7]. Because immune history is critical for understanding subsequent disease risk and protection, cohort studies are invaluable for studying protection against and pathogenesis of dengue disease. Here, we discuss the full value of longitudinal cohorts for: measuring basic determinants and immunological and virological characteristics of dengue disease in populations, estimating correlates of protection and disease risk, providing critical and timely information during outbreaks, enabling rapid development of new assays for diagnosis and surveillance, informing vaccine trial design, studying disease in a broader population context, building research capacity, and informing local and international policy-making (Table 1). Table 1 Ten ways cohort studies promote scientific research and infectious disease control Estimate basic infection and disease incidence, transmission parameters, and risk factors Identify BAY 11-7085 correlates of protection and disease risk Enable scientific studies of well-characterized samples with advanced scientific techniques Provide longitudinal samples MSH2 to study kinetics BAY 11-7085 of antibody and biomarker levels Inform vaccine trial design and evaluation Serve as sentinels during outbreaks to inform local and international policy decision-making Collect high-quality samples for diagnostic assay development Enable holistic studies of multiple diseases and environmental and socioeconomic factors Increase understanding of individual and intrinsic differences that drive immunity to pathogens Foster infectious disease infrastructure, research, and control in disease-affected countries in close collaboration with Ministries of Health Open in a separate window Review of dengue cohort studies We used PubMed to download all articles with the term ‘dengue’ in the title and ‘cohort’ in either the title or abstract (n=283, January 4, 2018). Titles and abstracts were screened to identify prospective cohort studies of dengue in healthy populations (some reviewed previously in [8C10]; we do not review infant cohorts here). We identified 28 cohort studies from 1964 to the present (Table 2). Table 2 Community-, school-, or household-based longitudinal prospective cohort studies of dengue (in chronological order) immunity correlates with infection and disease outcome. BAY 11-7085 Correlates of protection and risk Most studies of correlates of protection and risk have examined neutralizing antibody or ADE titers in non-random subsets of dengue cohorts using classical serological assays such as the plaque reduction neutralization test (PRNT) or ADE assays, although some use newer tools [27,32,35,49,50]. In a Thai cohort, neutralizing antibodies distinguished non-severe dengue fever (DF) cases from DHF/DSS cases infected with DENV3, but not DENV2 [51]. In the same cohort, antibody-dependent cellular cytotoxicity was BAY 11-7085 found to correlate with neutralizing antibody titers and IgG1 levels as well as viremia in DENV3 patients, but not with disease severity [52]. Another Thai cohort confirmed that PRNT titer does not perfectly correlate with protection, as individuals with high PRNT titers could still acquire symptomatic DENV infections [53]. Other cohort studies have compared inapparent to symptomatic DENV infections and.