Statistical considerations on real time and extended controlled temperature conditions (ECTC) stability data analysis of vaccines.

BACKGROUND: Although maintaining vaccines in a strict cold chain has cost and logistical implications in low- and middle-income countries, only a few vaccines have obtained approval for extended controlled temperature conditions (ECTC) application, which permits the administration of vaccines after storage outside of the cold chain for a defined period. We developed a methodology to evaluate stability data and calculate minimum release potency (MRP) in support of ECTC application. METHODS: The methodology is focused on statistical considerations consisting of stability data collection, statistical analysis plan, statistical modelling, and statistical report. It uses mock stability data from a hypothetical product and may serve as a helpful guide for other products. The statistical data analysis is performed using the R program which is an open-source program and validated using the SAS software. RESULTS: We developed a stability data testing scheme that included 24 lots with six-time points for up to 24 months under real-time and real condition (RT) in the cold chain samples stored at 2-8 °C and 12 lots with six timepoints for 14 days under ECTC samples stored at 40 °C. The log-transformed stability data met the linear regression assumptions and were poolable from representative lots with no significant lot variation. The linear regression analysis model with a common slope and intercept confirmed the stable antigen content over time under RT and ECTC by the mean regression line and 95% confidence interval. Based on the fitted models and the estimated coefficients, the antigen content value of 966 was derived as the MRP under RT for 24 months followed by 14 days under ECTC. CONCLUSION: The presented framework of statistical considerations, with practical methods and R program codes to perform statistical analysis, may serve as a guide for developing the CTC data for a vaccine's stability evaluation prospectively.

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial.

BACKGROUND: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented. METHODS: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood. RESULTS: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups. CONCLUSIONS: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups. CLINICAL TRIALS REGISTRATION: NCT05109559.

Seroepidemiological Reconstruction of Long-term Chikungunya Virus Circulation in Burkina Faso and Gabon.

Chikungunya virus (CHIKV) is a major public health concern worldwide. However, infection levels are rarely known, especially in Africa. We recruited individuals from Ouagadougou, Burkina Faso and Lambaréné, Gabon (age range, 1-55 years), tested their blood for CHIKV antibodies, and used serocatalytic models to reconstruct epidemiological histories. In Ouagadougou, 291 of 999 (29.1%) individuals were seropositive, ranging from 2% among those aged <10 years to 66% in those aged 40-55 years. We estimated there were 7 outbreaks since the 1970s but none since 2001, resulting in 600 000 infections in the city, none of which were reported. However, we could not definitively conclude whether infections were due to CHIKV or o'nyong-nyong, another alphavirus. In Lambaréné, 117 of 427 (27%) participants were seropositive. Our model identified a single outbreak sometime since 2007, consistent with the only reported CHIKV outbreak in the country. These findings suggest sporadic outbreaks in these settings and that the burden remains undetected or incorrectly attributed.

Dengue virus seroprevalence study in Bangphae district, Ratchaburi, Thailand: A cohort study in 2012-2015.

BACKGROUND: To determine the seroprevalence and transmission dynamics of dengue virus (DENV), age-stratified longitudinal serological surveys were conducted in Bangphae district, Ratchaburi province, Thailand, for 3 years between April 2012 and April 2015. METHODOLOGY: The surveys enrolled 2012 healthy children and adults between 1 and 55 years-of-age, and a longitudinal serosurvey of six repeated bleeds of the same cohort of individuals was conducted every 8 months for the first 2 years (M0, M8, M16) and every half a year (M24, M30, M36) for the rest of the study period. All samples were tested using in-house indirect sandwich dengue IgG ELISA to determine DENV antibody titer, and 640 paired samples which showed rising of DENV IgG titers in paired serum were further tested using in-house neutralization assay, Plaque Reduction Neutralization Test (PRNT50). PRINCIPAL FINDINGS: When compared against the gold standard based on the results of PRNT50, sensitivity and specificity of indirect ELISA were found to be both about 85%. The overall DENV IgG positivity determined by ELISA was 74.3% in 2012 and increased to 79.4% by the final sample collection in 2015. In our study sample, more than 98% of subjects older than 25 years were found to be seropositive. Among 518 IgG negative subjects at enrollment, the seroconversion rates were measured in paired bleeds; the rates (between successive visits, approximately 6 months) ranged between 4.8% (between M16 and M24) and 14.7% (between M0 and M8). The dominant serotype of primary DENV infection cases based on seroconversion was identified from the PRNT results and it was DENV-2. CONCLUSIONS: Our study documented high levels of seroprevalence and rate of transmission. Given the importance of the serostatus and disease burden in consideration for dengue vaccine introduction, our data could be used in decision-making on implementation of various dengue control and preventive measures.

Oral Cholera Vaccine Efficacy and Effectiveness.

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the "gold standard", effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV. Although the results of OCV effectiveness studies sometimes showed outliers, the tendency seen is for effectiveness of the vaccine used in public health settings to be somewhat higher than estimated in randomized controlled trials due to the influence of indirect herd protection. Efficacy and Effectiveness studies both generate important information about the vaccine performance characteristics and its impact when used in real world populations at risk for the disease.

Clinical and epidemiologic characteristics associated with dengue fever in 2011-2016 in Bang Phae district, Ratchaburi province, Thailand.

BACKGROUND: Dengue is a major public health problem in Thailand, but data are often focused on certain dengue-endemic areas. Methods: To better understand dengue epidemiology and clinical characteristics in Thailand, a fever surveillance study was conducted among patients aged 1-55 years, who presented with non-localized febrile illness at Bang Phae Community Hospital in Ratchaburi province, Thailand from October 2011 to September 2016. RESULTS: Among 951 febrile episodes, 130 were dengue-confirmed. Individuals aged 10-14 years were mostly affected, followed by those 15-19 years-of-age, with about 15% of dengue-confirmed cases from adults 25 years and older. There were annual peaks of dengue occurrence between June-November. Most prevalent serotype in circulation was DENV-2 in 2012, DENV-3 in 2014, and DENV-4 & -3 in 2015. Among dengue cases, 65% were accurately detected using the dengue NS1 RDT. Detection rate was similar between secondary and primary dengue cases where 66% of secondary vs. 60% of primary dengue cases had positive results on the NS1 RDT. Among dengue cases, 66% were clinically diagnosed with suspected dengue or DHF, prior to lab confirmation. Dengue was positively associated with rash, headache, hematemesis and alterations to consciousness, when compared to non-dengue. Dengue patients were 10.6 times more likely to be hospitalized, compared to non-dengue cases. Among dengue cases, 95 were secondary and 35 were primary infections. There were 8 suspected DHF cases and all were identified to be secondary dengue. Secondary dengue cases were 3.5 times more likely to be hospitalized compared to primary dengue cases. Although the majority of our dengue-positive patients were secondary dengue cases, with few patients showing manifestations of DHF, our dengue cases were mostly mild disease. Even among children < 10 years-of-age, 61% had secondary infection and the rate of secondary infection increased with age. CONCLUSION: While the majority of dengue-confirmed cases were children, almost three-quarters of dengue-confirmed cases in this study were secondary dengue. Our study results consistent with previous data from the country confirm the hyperendemic transmission of DENV in Thailand, even in the non-epidemic years. With various interventions becoming available for dengue prevention and control, including dengue vaccines, decision-making on future implementation strategies should be based on such burden of disease data.

Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan.

BACKGROUND: The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood. METHODS: Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid Fever Surveillance in Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral, and parasitic pathogens. Clinical metadata were also assessed. RESULTS: A total of 615 blood samples available for analysis originated from Burkina Faso (n = 53), Madagascar (n = 364), and Sudan (n = 198) and were taken from participants ranging in age from 0-19 years. Through the TaqMan-Array Card, at least 1 pathogen was detected in 62% (33 of 53), 24% (86 of 364), and 60% (118 of 198) of specimens from Burkina Faso, Madagascar, and Sudan, respectively. The leading identified pathogen overall was Plasmodium spp., accounting for 47% (25 of 53), 2.2% (8 of 364), and 45% (90 of 198) of AFI at the respective sites. In Madagascar, dengue virus was the most prevalent pathogen (10.2%). Overall, 69% (357 of 516) of patients with clinical diagnoses of malaria, respiratory infection, or gastrointestinal infection were prescribed a World Health Organization guideline-recommended empiric antibiotic, whereas only 45% (106 of 237) of patients with pathogens detected were treated with an antibiotic exerting likely activity. CONCLUSIONS: A PCR approach for identifying multiple bacterial, viral, and parasitic pathogens in whole blood unveiled a diversity of previously undetected pathogens in AFI cases and carries implications for the appropriate management of this common syndrome.

Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings.

BACKGROUND: In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon. METHODS: Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR. RESULTS: Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases. CONCLUSION: Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians' diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.

Clinical and epidemiologic characteristics associated with dengue fever in Mombasa, Kenya.

OBJECTIVES: Information on dengue in Africa is limited. To estimate the proportion of dengue-positive cases among febrile patients and describe clinical indicators of dengue, we conducted passive health facility-based fever surveillance in Mombasa, Kenya. METHODS: Non-malarial febrile patients between one and 55 years were enrolled at three health facilities between March 2016 and May 2017. Acute and convalescent blood samples were collected with an interval of 10-21 days. Acute samples were tested with dengue RDT and a selected subset with RT-PCR, and acute/convalescent samples with IgM/IgG ELISA. RESULTS: Among 482 enrollees, 295 (61.2%) were dengue-positive based on laboratory results. The surveillance covered the beginning of a dengue outbreak in April-May 2017, during which 73.9% of enrollees were dengue-positive. By contrast, during the non-outbreak period, 54.6% were dengue-positive. Dengue case status was positively associated with rash, fatigue, headache, retro-orbital pain, nausea/vomiting, nose bleeding, gum bleeding, loss of appetite, myalgia, and arthralgia. Dengue-positive cases in our study had mostly mild disease, with only two requiring observation, and no DHF. CONCLUSIONS: The clinical response was generally mild relative to what was observed in SE Asia and the Americas. Given the high level of DENV transmission in Mombasa, more data would be needed to further understand the disease burden and improve case detection for surveillance/monitoring of outbreaks.

The epidemiology of dengue outbreaks in 2016 and 2017 in Ouagadougou, Burkina Faso.

BACKGROUND: Dengue is prevalent in as many as 128 countries with more than 100 million clinical episodes reported annually and four billion people estimated to be at risk. While dengue fever is systematically diagnosed in large parts of Asia and South America, the disease burden in Africa is less well investigated. This report describes two consecutive dengue outbreaks in Ouagadougou, Burkina Faso in 2016 and 2017. METHODS: Blood samples of febrile patients received at Schiphra laboratory in Ouagadougou, Burkina Faso, were screened for dengue infection using SD Bioline Dengue Duo rapid diagnostic test kits (Standard Diagnostics, Suwon, Republic of Korea). RESULTS: A total of 1,397 and 1,882 cases were reported by a single laboratory in 2016 and 2017, respectively. Most cases were at least 15 years of age and the results corroborated reports from WHO indicating the circulation of three dengue virus serotypes in Burkina Faso. CONCLUSION: This study complements data from other, simultaneously conducted surveillance efforts, and indicates that the dengue disease burden might be underestimated in sub-Saharan African nations. Dengue surveillance should be enhanced in African settings to determine the burden more accurately, and accelerated efforts towards a dengue vaccine should be put in place.

Epidemiology and genetic diversity of circulating dengue viruses in Medellin, Colombia: a fever surveillance study.

BACKGROUND: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. METHODS: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. RESULTS: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. CONCLUSIONS: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.

Monoclonal antibody-based capture ELISA in the diagnosis of previous dengue infection.

BACKGROUND: Dengue is an important mosquito-borne disease. There is currently only one licensed vaccine for dengue prevention. The vaccine provides higher efficacy in pre-vaccination dengue-seropositive persons but a higher risk of subsequent more severe dengue in dengue-seronegative persons. It is recommended that the dengue vaccine may be given in dengue-seropositive individuals or as mass vaccination without individual pre-vaccination screening in areas where the dengue seroprevalence is > 80% in children aged 9 years. We evaluated a dengue specific immunoglobulin G monoclonal antibody-based capture enzyme-linked immunosorbent assay (MAb-ELISA) in the diagnosis of previous dengue infection using serum samples from the cohort study in Ratchaburi Province, Thailand. METHODS: The MAb-ELISA was compared to 70% plaque reduction neutralization test (PRNT70) in 453 serum samples from children aged 3-11 years in Ratchaburi Province, Thailand. RESULTS: The sensitivity and specificity of MAb-ELISA at the positive to negative (P/N) ratio cut-off level of > 3 were both 0.91 in the diagnosis of previous dengue infection, compared to PRNT70. The false positivity was mainly in Japanese encephalitis (JE) seropositive subjects. CONCLUSIONS: This research provides evidence that MAb-ELISA is useful for dengue seroprevalence study and dengue pre-vaccination screening. JE seropositivity was the major cause of false positive result in the study population.

Evaluating dengue burden in Africa in passive fever surveillance and seroprevalence studies: protocol of field studies of the Dengue Vaccine Initiative.

INTRODUCTION: Dengue is an important and well-documented public health problem in the Asia-Pacific and Latin American regions. However, in Africa, information on disease burden is limited to case reports and reports of sporadic outbreaks, thus hindering the implementation of public health actions for disease control. To gather evidence on the undocumented burden of dengue in Africa, epidemiological studies with standardised methods were launched in three locations in Africa. METHODS AND ANALYSIS: In 2014-2017, the Dengue Vaccine Initiative initiated field studies at three sites in Ouagadougou, Burkina Faso; Lambaréné, Gabon and Mombasa, Kenya to obtain comparable incidence data on dengue and assess its burden through standardised hospital-based surveillance and community-based serological methods. Multidisciplinary measurements of the burden of dengue were obtained through field studies that included passive facility-based fever surveillance, cost-of-illness surveys, serological surveys and healthcare utilisation surveys. All three sites conducted case detection using standardised procedures with uniform laboratory assays to diagnose dengue. Healthcare utilisation surveys were conducted to adjust population denominators in incidence calculations for differing healthcare seeking patterns. The fever surveillance data will allow calculation of age-specific incidence rates and comparison of symptomatic presentation between patients with dengue and non-dengue using multivariable logistic regression. Serological surveys assessed changes in immune status of cohorts of approximately 3000 randomly selected residents at each site at 6-month intervals. The age-stratified serosurvey data will allow calculation of seroprevalence and force of infection of dengue. Cost-of-illness evaluations were conducted among patients with acute dengue by Rapid Diagnostic Test. ETHICS AND DISSEMINATION: By standardising methods to evaluate dengue burden across several sites in Africa, these studies will generate evidence for dengue burden in Africa and data will be disseminated as publication in peer-review journals in 2018.

A systematic review of the economic impact of rapid diagnostic tests for dengue.

BACKGROUND: Dengue fever is rapidly expanding geographically, with about half of the world's population now at risk. Among the various diagnostic options, rapid diagnostic tests (RDTs) are convenient and prompt, but limited in terms of accuracy and availability. METHODS: A systematic review was conducted of published data on the use of RDTs for dengue with respect to their economic impact. The search was conducted with combinations of key search terms, including "((Dengue[Title]) AND cost/economic)" and "rapid diagnostic test/assay (or point-of-care)". Articles with insufficient report on cost/economic aspect of dengue RDTs, usually on comparison of different RDTs or assessment of novel rapid diagnostic tools, were excluded. This review has been registered in the PROSPERO International prospective register of systematic reviews (registry #: CRD42015017775). RESULTS: Eleven articles were found through advanced search on Pubmed. From Embase and Web of Science, two and 14 articles were obtained, respectively. After removal of duplicate items, title screening was done on 21 published works and 12 titles, including 2 meeting abstracts, were selected for abstract review. For full-text review, by two independent reviewers, 5 articles and 1 meeting abstract were selected. Among these, the abstract was referring to the same study results as one of the articles. After full text review, two studies (two articles and one abstract) were found to report on cost-wise or economic benefits of dengue RDTs and were selected for data extraction. One study found satisfactory performance of IgM-based Panbio RDT, concluding that it would be cost-effective in endemic settings. The second study was a modeling analysis and showed that a dengue RDT would not be advantageous in terms of cost and effectiveness compared to current practice of antibiotics prescription for acute febrile illness. CONCLUSIONS: Despite growing use of RDTs in research and clinical settings, there were limited data to demonstrate an economic impact. The available two studies reached different conclusions on the cost-effectiveness of dengue RDTs, although only one of the two studies reported outcomes from cost-effectiveness analysis of dengue and the other was considering febrile illness more generally. Evidence of such an impact would require further quantitative economic studies.

An Update on Zika Virus in Asia.

Zika virus (ZIKV) was first isolated in Asia from mosquitoes from Malaysia in 1966. However, the incidence of Zika and Zika-related neurological complications in Asia is not well known. The few studies of Zika in Asia have been inconsistent in pointing to likely transmission levels, with some studies suggesting substantial transmission and others not. Interpretation of existing epidemiological and public health data from Asia is constrained by the non-specific symptomatology of Zika, the high proportion of subclinical ZIKV infections, relatively low viremia, and the lack of accurate serological assays. Here, we update the status of Zika cases from countries in Asia, and highlight some key knowledge gaps. In particular, accurate determinations of the incidence of Zika-related congenital Zika syndrome should be a priority for Zika research in Asia. Additional information will be critical to make informed strategies for the prevention and control of this global public health threat.

Dengue virus serological prevalence and seroconversion rates in children and adults in Medellin, Colombia: implications for vaccine introduction.

BACKGROUND: Dengue is an important public health problem worldwide. A vaccine has recently been licensed in some countries of Latin America and Asia. Recommendations for dengue vaccine introduction include endemicity and a high serological prevalence of dengue in the territories considering its introduction. METHODS: A community-based survey was conducted to estimate dengue seroprevalence and age-specific seroconversion rates in a community in Medellin, Colombia, using a dengue serological test (IgG indirect ELISA). Residents were selected at random and were first screened for dengue infection; they were then followed over 2.5 years. RESULTS: A total of 3684 individuals aged between 1 and 65 years participated in at least one survey. The overall dengue seroprevalence was 61%, and only 3.3% of seropositive subjects self-reported a past history of dengue. Among dengue virus (DENV)-naïve subjects with more than two visits (n=1002), the overall seroconversion rate was 8.7% (95% confidence interval 7.3-10.4) per 1000 person-months, over the study period. Overall, the mean age of DENV prevalent subjects was significantly higher than the mean age of seroconverted subjects. Specifically, DENV seropositivity over 70% was observed in participants over 21 years old. Serotype-specific plaque-reduction neutralization tests (PRNT) revealed that all four dengue serotypes were circulating, with DENV4 being most prevalent. CONCLUSIONS: These laboratory-based findings could inform dengue vaccine decisions, as they provide age-specific seroprevalence and seroconversion data, evidencing permanent and ongoing dengue transmission in the study area. This study provides evidence for the existing rates of secondary and heterotypic responses, presenting a challenge that must be addressed adequately by the new vaccine candidates.

Points for Consideration for dengue vaccine introduction - recommendations by the Dengue Vaccine Initiative.

Dengue is a public health problem in the tropics and subtropics. There are several vaccine candidates in clinical development. However, there may be gaps in the new vaccine introduction after vaccine licensure before it becomes available in developing countries. In anticipation of the first dengue vaccine candidate to be licensed, Dengue Vaccine Initiative (DVI) and, its predecessor, Pediatric Dengue Vaccine Initiative (PDVI) have been working on points for consideration to accelerate evidence-based dengue vaccine introduction, once a vaccine becomes available. In this paper, we review the history of PDVI and its successor, the DVI, and elaborate on the points of consideration for dengue vaccine introduction.