Past Dengue Research Articles

Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages

BackgroundWhile dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there has been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity.MethodsPrimary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF = 8) or dengue haemorrhagic fever (DHF = 8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF.ResultsSignificantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p = 0.01, median = 45.69 pg/ml), but lower levels when NS1 was co-cultured with HDL (p = 0.05, median = 4.617 pg/ml). MDMs of those with past DHF produced higher levels of IL-1β when NS1 was co-cultured with PAF (p = 0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF.ConclusionsAs RPLP2 is important in DENV replication, regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions.

Dengue NS1 interaction with lipids alters its pathogenic effects on monocyte derived macrophages.

While dengue NS1 antigen has been shown to be associated with disease pathogenesis in some studies, it has not been linked in other studies, with the reasons remaining unclear. NS1 antigen levels in acute dengue are often associated with increased disease severity, but there have been a wide variation in results based on past dengue infection and infecting dengue virus (DENV) serotype. As NS1 engages with many host lipids, we hypothesize that the type of NS1-lipid interactions alters its pathogenicity. Primary human monocyte derived macrophages (MDMs) were co-cultured with NS1 alone or with HDL, LDL, LPS and/or platelet activating factor (PAF) from individuals with a history of past dengue fever (DF=8) or dengue haemorrhagic fever (DHF=8). IL-1β levels were measured in culture supernatants, and gene expression analysis carried out in MDMs. Monocyte subpopulations were assessed by flow cytometry. Hierarchical cluster analysis with Euclidean distance calculations were used to differentiate clusters. Differentially expressed variables were extracted and a classifier model was developed to differentiate between past DF and DHF. Significantly higher levels of IL-1β were seen in culture supernatants when NS1 was co-cultured with LDL (p=0.01), but with lower levels with HDL (p=0.05). MDMs of those past DHF produced more IL-1β when NS1 with PAF (p=0.02). MDMs of individuals with past DHF, were significantly more likely to down-regulate RPLP2 gene expression when macrophages were co-cultured with either PAF alone, or NS1 combined with PAF, or NS1 combined with LDL. When NS1 was co-cultured with PAF, HDL or LDL two clusters were detected based on IL10 expression, but these did not differentiate those with past DF or DHF. As RPLP2 is important in DENV replication and in regulating cellular stress responses and immune responses and IL-10 is associated with severe disease, it would be important to further explore how differential expression of RPLP2 and IL-10 could lead to disease pathogenesis based on NS1 and lipid interactions.

Dengue incidence forecasting model in Magalang, Pampanga using time series analysis

This study aimed to provide an Auto-Regressive Integrated Moving Average (ARIMA) model that can predict dengue incidence in Magalang, Pampanga based on the past dengue incidences & climate variables from 2016 to 2019 and identify significant predictor/predictors among the climate variables. Weekly dengue incidence and climatological data from January 2016 to December 2019 were gathered and considered as the dependent and independent variables, respectively. Then, the Expert Modeler in IBM SPSS 22 automatically selected and estimated the best fitting ARIMA model for one dependent variable series. The created model was then used to forecast dengue incidence for the 52-week period of 2020, employing quarterly, semi-annual, and annual forecasting. A one-way ANOVA was conducted to evaluate differences among the four groups, followed by a post hoc Scheffe test to determine which groups differed from each other. Additionally, the Diebold-Mariano (DM) test was utilized to validate the forecasting performance of the ARIMA model. The non-seasonal ARIMA (0,1,6) model, with the sum of rainfall as the sole predictor from seven candidate predictors, was identified as the best fit. Model fit statistics indicated a stationary R-squared value of 0.739. The Ljung-Box statistics test value of 0.344, deemed not significant, confirmed correct model specification. One-way ANOVA analysis revealed a significant difference among the four groups, with an F value of 34.37 and a p-value approaching zero. Post hoc Scheffe tests further indicated a significant difference between the observed dataset and both semi-annual and annual forecasting, with p-values of 0.014 and approaching zero, respectively. However, no significant difference was observed between the observed dataset and quarterly forecasting, with a p-value of 0.281. Moreover, DM test statistics revealed that quarterly forecasting outperformed both annual and semi-annual forecasting. This suggests that the non-seasonal ARIMA (0,1,6) model, with the sum of rainfall as a predictor, effectively predicts future dengue incidences using quarterly forecasting.

Safety and durable immunogenicity of the TV005 tetravalent dengue vaccine, across serotypes and age groups, in dengue-endemic Bangladesh: a randomised, controlled trial

Morbidity and mortality from dengue virus (DENV) is rapidly growing in the large populations of south Asia. Few formal evaluations of candidate dengue vaccine candidates have been undertaken in India, Pakistan, or Bangladesh. Tetravalent vaccines must be tested for safety and immunogenicity in all age groups and in those previously exposed and naive to DENV infections. TV005 is a live, attenuated tetravalent dengue vaccine. We evaluated the safety and immunogenicity of a single dose of TV005 across age groups in dengue-endemic Bangladesh. We performed a randomised, placebo-controlled age de-escalating clinical trial of TV005 at a single clinical site in dengue-endemic Dhaka, Bangladesh, following a technology transfer from the USA. Healthy (as determined by history, clinical examination, and safety laboratory test results) volunteers aged 1-50 years were randomly assigned 3:1 (stratified by four age groups) to receive a single dose of TV005 vaccine or placebo. Participants were followed up for 3 years. The study was double blind and was unmasked at day 180; outcome assessors, clinic staff, and volunteers remained blind throughout. Primary outcomes were safety, evaluated per-protocol as proportion of volunteers with solicited related adverse events of any severity through 28 days post dosing, and post-vaccination seropositivity by day 180 using serotype-specific neutralising antibodies (PRNT50 ≥10). Secondary outcomes included viremia, impact of past dengue exposure, and durability of antibody responses. This study is registered with Clinicaltrials.gov, NCT02678455, and is complete. Between March 13, 2016, and Feb 14, 2017, 192 volunteers were enrolled into four age groups (adults [18-50 years; 20 male and 28 female], adolescents [11-17 years; 27 male and 21 female], children [5-10 years; 15 male and 33 female], and young children [1-4 years; 29 male and 19 female]) with 48 participant per group. All participants were Bangladeshi. Vaccination was well tolerated and most adverse events were mild. Rash was the most common vaccine-associated solicited adverse event, in 37 (26%) of 144 vaccine recipients versus six (12%) of 48 placebo recipients; followed by fever in seven (5% of 144) and arthralgias in seven (6% of 108), which were only observed in vaccine recipients. Post-vaccine, volunteers of all ages (n=142) were seropositive to most serotypes with 118 (83%) seropositive to DENV 1, 141 (99%) to DENV 2, 137 (96%) to DENV 3, and 124 (87%) to DENV 4, overall by day 180. Post-vaccination, viraemia was not consistently found and antibody titres were higher (10-15-fold for DENV 1-3 and 1·6-fold for DENV 4) in individuals with past dengue exposure compared with the dengue-naive participants (DENV 1 mean 480 [SD 4·0] vs 32 [2·4], DENV 2 1042 [3·2] vs 105 [3·1], DENV 3 1406 [2·8] vs 129 [4·7], and DENV 4 105 [3·3] vs 65 [3·1], respectively). Antibody titres to all serotypes remained stable in most adults (63-86%) after 3 years of follow-up. However, as expected for individuals without past exposure to dengue, titres for DENV 1, 3, and 4 waned by 3 years in the youngest (1-4 year old) cohort (69% seropositive for DENV 2 and 22-28% seropositive for DENV 1, 3, and 4). With 3 years of follow-up, the single-dose tetravalent dengue vaccine, TV005, was well tolerated and immunogenic for all four serotypes in young children to adults, including individuals with no previous dengue exposure. National Institutes of Health-National Institute of Allergy and Infectious Diseases Intramural Research Program and Johns Hopkins University. For the Bangla translation of the abstract see Supplementary Materials section.

Predicting the dengue cluster outbreak dynamics in Yogyakarta, Indonesia: a modelling study.

Human mobility and climate conditions are recognised key drivers of dengue transmission, but their combined and individual role in the local spatiotemporal clustering of dengue cases is not well understood. This study investigated the effects of human mobility and weather conditions on dengue risk in an urban area in Yogyakarta, Indonesia. We established a Bayesian spatiotemporal model for neighbourhood outbreak prediction and evaluated the performances of two different approaches for constructing an adjacency matrix: one based on geographical proximity and the other based on human mobility patterns. We used population, weather conditions, and past dengue cases as predictors using a flexible distributed lag approach. The human mobility data were estimated based on proxies from social media. Unseen data from February 2017 to January 2020 were used to estimate the one-month ahead prediction accuracy of the model. When human mobility proxies were included in the spatial covariance structure, the model fit improved in terms of the log score (from 1.748 to 1.561) and the mean absolute error (from 0.676 to 0.522) based on the validation data. Additionally, showed only few observations outside the credible interval of predictions (1.48%) and weather conditions were not found to contribute additionally to the clustering of cases at this scale. The study shows that it is possible to make highly accurate predictions of the within-city cluster dynamics of dengue using mobility proxies from social media combined with disease surveillance data. These insights are important for proactive and timely outbreak management of dengue. Swedish Research Council Formas, Umeå Centre for Global Health Research, Swedish Council for Working Life and Social Research, Swedish research council VINNOVA and Alexander von Humboldt Foundation (Germany).

Effect of previous episode of symptomatic dengue infection on recent dengue infection in children

Background: Approximately 390 million people worldwide are affected by dengue fever each year, >70% of them are from Asia. It is thought that antibody enhancement during the subsequent infections with dengue virus can cause more severe form of disease called dengue haemorrhagic fever (DHF). This study aims to observe the effect of prior dengue infection on recent infection. Methods: This retrospective record based descriptive-analytical study was conducted from July 2021 to December 2021 in paediatrics department of Bangabandhu Sheikh Mujib Medical University, Dhaka. Medical records of all admitted confirmed cases of dengue fever during the study period were reviewed retrospectively to find out past symptomatic dengue infection ,which further verified by parents over phone. Finally 98 patients were analyzed after exclusion. Results: Among 98 studied patients, 45 (45%) experienced DHF and 15 (15.3%) diagnosed with DSS. There was no significant (p>0.05) difference of age and sex between patients of DF, DHF and DSS. Majority of the patients 79 (80.6%) did not have a past history of documented symptomatic dengue infection. Here, 9 (23.6%) out of 38 DF patient, 8 (17.7%) out of 45 DHF patient and only 2 (13.3%) out of 15 patient with DSS had past symptomatic dengue infection. Maximum patients (92, 93.8%) were treated with isotonic fluid, 39 patients got colloid (39, 36.79%). This study found no significant (p>0.05) difference between DF, DHF and DSS with or without past symptomatic dengue infection. Conclusions: In our study we noticed that there was no increase in dengue morbidity with documented previous symptomatic dengue infection.

Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection.

To further understand the role of NS1-specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody subclass profiles and NS1-specific memory B-cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess NS1-specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1-specific NS1-Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross-reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.

Serological Evidence of Zika virus Circulation with Dengue and Chikungunya Infections in Sri Lanka from 2017.

Arbovirus diseases remain a public health threat in Sri Lanka. Dengue is endemic and two outbreaks of chikungunya infections have been reported. There is limited data on Zika virus (ZIKV) infections in Sri Lanka, and this could be due to a lack of comprehensive ZIKV surveillance. Our aim was to determine the presence of antibodies to dengue, chikungunya, and Zika infections in adults from a suburban population in Sri Lanka. A total of 149 healthy adult volunteers over 18 years of age (mean age: 43±14 years, males - 43%), with no prior diagnosed arboviral infections and no history of overseas travel, participated in the study. ELISA and neutralization assays were carried out to detect past dengue, chikungunya, or Zika infections. A total of 94.6% (141/149) of the participants demonstrated dengue IgG antibodies, 37.5% (56/149) were positive for chikungunya IgG, and 5.3% (8/149) were positive for anti-ZIKV IgG antibodies. Neutralization assays confirmed ZIKV-specific antibodies in 6.7% (10/149), when 40/149 of the participating population were tested. This clearly demonstrated past ZIKV infections in this population. In addition, this study indicates that >90% of individuals had asymptomatic dengue but no serious symptoms. These results provide a cross-sectional view on the DENV, ZIKV, and CHIKV epidemic status and demonstrate a need for the implementation of enhanced surveillance and more effective measures against the spread of these arbovirus diseases.

Seroepidemiological Study of Dengue Virus Infection Suspected Cases in Burkina Faso

Dengue fever is a mosquito-borne disease caused by four related but antigenically distinct dengue viruses. In the last half-century, the prevalence of dengue fever has increased dramatically (up to 30%) worldwide, especially in Sub-Saharan Africa. In Burkina Faso, the last dengue epidemic occurred in 2016, and the epidemiological situation is still poorly documented at the national level. Therefore, the present study aimed to conduct a sentinel seroepidemiology of suspected dengue virus infections from 2017 to 2020 at Charles de Gaulle University Pediatric Hospital Center of Ouagadougou. This investigation was designed to be a descriptive and analytical study. Patients with suspected cases of dengue fever were recruited from January 2017 to December 2020 during general medicine consultation and referred to Charles de Gaulle University Pediatric Hospital Center of Ouagadougou for the serological diagnosis of dengue. Venous blood was collected in dry or EDTA tubes and tested for DENV NS1 antigen, anti-dengue IgM, and anti-dengue IgG using SD Bioline Dengue Duo Rapid Detection Kit (Standard Diagnostic Inc., Korea). A total of 3400 blood samples from clinically suspected dengue cases were analyzed, of which 1784 (52.5%) were males, and 1616 (47.5%) were females. Among the 3400 patients included in the study, 661 (19.4%) were tested at least positive for NS1 antigen, anti-dengue IgM or anti-IgG. Among them, individuals positive for IgG suggesting past dengue virus infection were found in more than a third of 262 (7.7%) of the cases. Approximately, 80.0% (2705/3400) dengue suspected cases and 85.5% (341/399) early or primary dengue infections were recorded in the last four months of the study (September to December 2020), with a peak in mid-October and mid-November. There was no statistically significant difference in seroprevalence between males and females (p = 0.7), but an increasing seropositivity trend with age, from 11.6% for the patient under 5 years group to 39.7% for 30 years and over age group were noted. This study puts in evidence a considerable level of transmission of dengue viruses in Burkina Faso and provides baseline seroprevalence data. The recurrent outbreaks of dengue infection in multiple geographical areas need comprehensive surveillance and a diagnostic system to identify the actual burden and pinpoint the risk factors. A larger study is, therefore, needed to determine the actual prevalence of dengue in Burkina Faso and map the serotypes.

An Audit of Clinical Cases of Dengue Fever and the Usage of Platelets in Such Cases in a Tertiary Care Hospital in Hyderabad

Background and Objectives: Dengue is an acute self-limited systemic viral infection caused by the dengue virus of the family Flaviviridae. The incidence of dengue fever has been increasing for the past few years and dengue has become a global problem. The current data required for further improving the treatment policies are scanty. Our study aims to capture the demographic and clinical characteristics of the patients enrolled in the study, to see any correlation between thrombocytopenia and bleeding tendencies and other transfusion-related parameters. Methods: The study is a prospective cohort study. All seropositive dengue cases were included in the study. A format was prepared for documenting the demographic data, history, clinical characteristics, spectrum of the disease, the laboratory details of the patient (platelet count, prothrombin time, activated partial thromboplastin time, Hematocrit, and indication). All the transfusion requirement data were collected from the blood center registers. Overall mortality in the study group, number of hospital readmissions, and episodes of exacerbation of symptoms was recorded separately. Results: A total of 270 cases were included in the audit who fulfilled the inclusion and exclusion criteria. The median age of the patient pool was 27 (4–66 years range). Twenty-six percent of the cases developed hemorrhages. Eighty-four single-donor platelets (SDPs) and 340 random-donor platelets (RDPs) were used. A mean of 270 ml of products was transfused per patient. The mortality rate was 0.8%. The mean duration of hospitalization was 1 week. In 72% of cases, platelet count was restored in single-unit transfusion. Ninety-nine percent of the product utilization were within the guidelines recommended. Conclusion: A good monthly audit of blood product utilization is a good guide for treatment. Quality control and rational use of SDPs and RDPs are important in sick and thrombocytopenic patients resulting in better clinical outcomes.

Assessment of dengue virus threat to blood safety and community health: A single center study in northern Egypt

BackgroundThe risk of transfusion transmitted dengue (DENV) is increasingly recognized and poses a risk to blood safety as well as spreading into non-immune communities. ObjectivesTo determine dengue serological profile, environmental risk, knowledge, and preventive measures among blood donors in a national blood bank in northern Egypt. MethodsA total of 500 blood donors were enrolled into this study between June and September 2018. Socio-demographic and medical data were collected using a predesigned questionnaire. Blood samples were screened for anti-DENV IgM, anti-DENV IgG and non-structural protein 1 antigen (DENV-NS1 antigen). ResultsHistory of past dengue exposure was identified in 10.2% of blood donors. No samples (0.0%) tested positive for anti-DENV IgG, IgM or NS1 antigen. At the time of blood donation, no individuals had any symptoms suggestive of a dengue-related illness. Dengue exposure strongly correlated with travel to the Kingdom of Saudi Arabia (KSA), Sudan and the El-Quseir outbreak area in Egypt. Knowledge of dengue and prevention methods was found to be substantially deficient, and the relatively higher level of knowledge among exposed donors did not translate into appropriate preventative measures. ConclusionsOur risk assessment shows the impact of travel on DENV exposure and highlights its potential threat to disease spread in Egypt. Dengue awareness programs are urgently needed for effective prevention of transmission.

Forecasting of dengue hemorrhages fever cases with autoregression distributed lag model using Poisson regression approach

Dengue hemorrhages fever (DHF) is an infectious disease epidemic in the community. DHF is caused by a virus that is transmitted through the bite of mosquitoes Aedes sp. The aim of this research was to develop and validate a forecasting model that could predict dengue fever (DHF) cases in Bandung, West Java, Indonesia. Model of dengue fever is developed using time series Poisson multivariate regression. Poisson regression is a generalized linear model form of regression analysis used to model count data and contingency tables. Poisson regression assumes the response variable has a Poisson distribution and the logarithm of its expected value can be modeled by a linear combination of unknown parameters. Here, a time series Poisson multivariate regression model was developed using monthly mean temperature and cumulative rainfall over the period 2001–2016. Cross-correlation function between response and predictor is used to decide the lag parameter optimum in autoregression distributed lag model. Model selection and validation were based on the Akaike’s information criterion, mean square error, mean absolute percentage error, and residuals diagnostic test. The R-square obtained is 0.78, means that the temperature, rainfall, past dengue fever cases, season, and trend could explain 78% of the variance of monthly dengue distribution.

A Study to Assess the Knowledge, Awareness and Preventive Practices Regarding Dengue Fever among Patients Visiting Medical OPD at Civil Hospital, Nadiad City

Background: Dengue, the mosquito borne disease has become global public health problem. The present study was conducted to assess the knowledge, awareness and preventive practices regarding dengue fever among patients visiting medical OPD at civil hospital, Nadiad City.
 Methods: A cross-sectional study was conducted with 100 randomly selected patients from Civil Hospital, Nadiad during September to November 2021. A structured questionnaire was used covering socio-demographic characteristics of the participants, knowledge, awareness, treatment and preventive practices regarding dengue fever. Data were analyzed using descriptive, inferential.
 Results: Of the 100 participants recruited in the study, 47% were females and 53% were males. A majority 63% belong to 15 - 45 years of age, were Hindus 80%, studied up to primary level (68%), resided in the urban area (64%) and 22% had past dengue exposure. Although patients had heard of dengue, the overall mean score of knowledge, awareness and preventive practices regarding dengue fever was 16.5 ± 1.4, with 23%, 68%, and 9% participants having good, average and poor knowledge respectively regarding dengue.
 Conclusion: It was evident that the patients have the sufficient knowledge regarding dengue fever and its prevention, but execution of this knowledge in putting the dengue preventive measures to practice was poor. There is a need to create awareness for hygiene and cleanliness to prevent mosquito bites.

Seroprevalence of Dengue Infection Using IgG Capture ELISA in India, 2017-2018.

We conducted a nationally representative population-based survey in 60 districts from 15 Indian states covering all five geographic regions during 2017-2018 to estimate the age specific seroprevalence of dengue. Of the 12,300 sera collected, 4,955 were positive for IgG antibodies against dengue virus using IgG Indirect ELISA indicating past dengue infection. We tested 4,948 sera (seven had inadequate volume) positive for IgG antibodies on indirect ELISA using anti-dengue IgG capture ELISA to estimate the proportion of dengue infections with high antibody titers, suggestive of acute or recent secondary infection. Of the 4,948 sera tested, 529 (10.7%; 95% CI: 9.4-12.1) were seropositive on IgG capture ELISA. The proportions of dengue infections with high titers were 1.1% in the northeastern, 1.5% in the eastern, 6.2% in the western, 12.2% in the southern, and 16.7% in the northern region. The distribution of dengue infections varied across geographic regions, with a higher proportion of infections with high antibody titer in the northern and southern regions of India. The study findings could be useful for planning facilities for clinical management of dengue infections.

Local and Global Stability Analysis of Dengue Disease with Vaccination and Optimal Control

Dengue fever is a disease that has spread all over the world, including Thailand. Dengue is caused by a virus and there are four distinct serotypes of the virus that cause dengue DENV-1, DENV-2, DENV-3, and DENV-4. The dengue viruses are transmitted by two species of the Aedes mosquitoes, the Aedes aegypti, and the Aedes albopictus. Currently, the dengue vaccine used in Thailand is chimeric yellow tetravalent dengue (CYD-TDV). This research presents optimal control which studies the vaccination only in individuals with a documented past dengue infection (seropositive), regardless of the serotypes of infection causing the initial infection by the disease. The analysis of dengue transmission model is used to establish the local asymptotically stabilities. The property of symmetry in the Lyapunov function an import role in achieving this global asymptotically stabilities. The optimal control systems are shown in numerical solutions and conclusions. The result shows that the control resulted in a significant reduction in the number of infected humans and infected vectors.

Optimal Control of Dengue Transmission with Vaccination

Dengue disease is caused by four serotypes of the dengue virus: DEN-1, DEN-2, DEN-3, and DEN-4. The chimeric yellow fever dengue tetravalent dengue vaccine (CYD-TDV) is a vaccine currently used in Thailand. This research investigates what the optimal control is when only individuals having documented past dengue infection history are vaccinated. This is the present practice in Thailand and is the latest recommendation of the WHO. The model used is the Susceptible-Infected-Recovered (SIR) model in series configuration for the human population and the Susceptible-Infected (SI) model for the vector population. Both dynamical models for the two populations were recast as optimal control problems with two optimal control parameters. The analysis showed that the equilibrium states were locally asymptotically stable. The numerical solution of the control systems and conclusions are presented.

Target product profile for a dengue pre-vaccination screening test.

With increasing geographic spread, frequency, and magnitude of outbreaks, dengue continues to pose a major public health threat worldwide. Dengvaxia, a dengue live-attenuated tetravalent vaccine, was licensed in 2015, but post hoc analyses of long-term data showed serostatus-dependent vaccine performance with an excess risk of hospitalized and severe dengue in seronegative vaccine recipients. The World Health Organization (WHO) recommended that only persons with evidence of past dengue infection should receive the vaccine. A test for pre-vaccination screening for dengue serostatus is needed. To develop the target product profile (TPP) for a dengue pre-vaccination screening test, face-to-face consultative meetings were organized with follow-up regional consultations. A technical working group was formed to develop consensus on a reference test against which candidate pre-vaccination screening tests could be compared. The group also reviewed current diagnostic landscape and the need to accelerate the evaluation, regulatory approval, and policy development of tests that can identify seropositive individuals and maximize public health impact of vaccination while avoiding the risk of hospitalization in dengue-naive individuals. Pre-vaccination screening strategies will benefit from rapid diagnostic tests (RDTs) that are affordable, sensitive, and specific and can be used at the point of care (POC). The TPP described the minimum and ideal characteristics of a dengue pre-vaccination screening RDT with an emphasis on high specificity. The group also made suggestions for accelerating access to these RDTs through streamlining regulatory approval and policy development. Risk and benefit based on what can be achieved with RDTs meeting minimal and optimal characteristics in the TPP across a range of seroprevalences were defined. The final choice of RDTs in each country will depend on the performance of the RDT, dengue seroprevalence in the target population, tolerance of risk, and cost-effectiveness.

Development and validation of an assay for detection of Japanese encephalitis virus specific antibody responses.

Although immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity. 22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n = 175) (OR 5.3, 95% CI 3.3 to 8.3). As our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.

Explicit characterization of human population connectivity reveals long run persistence of interregional dengue shocks.

Dengue is hyper-endemic in Singapore and Malaysia, and daily movement rates between the two countries are consistently high, allowing inference on the role of local transmission and imported dengue cases. This paper describes a custom built sparse space–time autoregressive (SSTAR) model to infer and forecast contemporaneous and future dengue transmission patterns in Singapore and 16 administrative regions within Malaysia, taking into account connectivity and geographical adjacency between regions as well as climatic factors. A modification to forecast impulse responses is developed for the case of the SSTAR and is used to simulate changes in dengue transmission in neighbouring regions following a disturbance. The results indicate that there are long-term responses of the neighbouring regions to shocks in a region. By computation of variable inclusion probabilities, we found that each region’s own past counts were important to describe contemporaneous case counts. In 15 out of 16 regions, other regions case counts were important to describe contemporaneous case counts even after controlling for past local dengue transmissions and exogenous factors. Leave-one-region-out analysis using SSTAR showed that dengue transmission counts could be reconstructed for 13 of 16 regions' counts using external dengue transmissions compared to a climate only approach. Lastly, one to four week ahead forecasts from the SSTAR were more accurate than baseline univariate autoregressions.

Ethics of a partially effective dengue vaccine: Lessons from the Philippines

Dengvaxia, a chimeric yellow fever tetravalent dengue vaccine developed by SanofiPasteur is widely licensed in dengue-endemic countries. In a large cohort study Dengvaxia was found to partially protect children who had prior dengue virus (DENV) infections but sensitized seronegative children to breakthrough DENV disease of enhanced severity. In 2019, the European Medicines Agency and the US FDA issued licenses that reconciled safety issues by restricting vaccine to individuals with prior dengue infections. Using revised Dengvaxia efficacy and safety data we sought to estimate hospitalized and severe dengue cases among the more than 800,000 9 year-old children vaccinated in the Philippines. Despite an overall vaccine efficacy of 69% during 4 years post-vaccination we project there will be more than one thousand vaccinated seronegative and seropositive children hospitalized for severe dengue. Assisting these children through a program of enhanced surveillance leading to improved care deserves widespread support. Clinical responses observed during breakthrough dengue infections in vaccinated individuals counsel prudence in design of vaccine policies. Recommendations concerning continued use of this dengue vaccine are: (1) obtain a better definition of vaccine efficacy and safety through enhanced phase 4 surveillance, (2) obtain a valid, accessible, sensitive, specific and affordable serological test that identifies past wild-type dengue virus infection and (3) clarify safety and efficacy of Dengvaxia in flavivirus immunes. In the absence of an acceptable serological screening test these unresolved ethical issues suggest Dengvaxia be given only to those signing informed consent.