Vaccine development for mosquito-borne viral diseases.

Mosquito-borne viral diseases are a group of viral illnesses that are predominantly transmitted by mosquitoes, including viruses from the Togaviridae and Flaviviridae families. In recent years, outbreaks caused by Dengue and Zika viruses from the Flaviviridae family, and Chikungunya virus from the Togaviridae family, have raised significant concerns for public health. However, there are currently no safe and effective vaccines available for these viruses, except for CYD-TDV, which has been licensed for Dengue virus. Efforts to control the transmission of COVID-19, such as home quarantine and travel restrictions, have somewhat limited the spread of mosquito-borne viral diseases. Several vaccine platforms, including inactivated vaccines, viral-vector vaccines, live attenuated vaccines, protein vaccines, and nucleic acid vaccines, are being developed to combat these viruses. This review analyzes the various vaccine platforms against Dengue, Zika, and Chikungunya viruses and provides valuable insights for responding to potential outbreaks.

Dengue vaccine acceptability before and after the availability of COVID-19 vaccines in Puerto Rico.

Dengue is a growing public health threat, causing approximately 400 million infections annually. In June 2021, the Advisory Committee on Immunization Practices recommended the first dengue vaccine (CYD-TDV) for children aged 9-16 years with a previous dengue infection, living in endemic areas, such as Puerto Rico (PR). As the COVID-19 pandemic affected vaccine intention worldwide, we assessed dengue vaccine intention before (pre-COVID) and after (post-COVID) COVID-19 vaccine availability among participants enrolled in the Communities Organized to Prevent Arboviruses (COPA) cohort to prepare for dengue vaccine implementation in PR. We used logistic regression models to evaluate changes in dengue vaccine intention by interview timing and participant characteristics. Among 2,513 participants pre-COVID, 2,512 answered the dengue vaccine intention question for themselves, and 1,564 answered relative to their children. Post-COVID, dengue vaccine intention in adults increased for themselves from 73.4% to 84.5% (adjusted odds ratio (aOR) = 2.27, 95%CI: 1.90-2.71) and relative to their children from 75.6% to 85.5% (aOR = 2.21, 95%CI: 1.75-2.78). Among all participants, groups with higher dengue vaccine intention included those who reported previous year influenza vaccine uptake and those who reported being frequently bitten by mosquitos, compared to those who did not. Adult males were also more likely to intend to vaccinate themselves than females. Respondents who were employed or in school were less likely to intend to vaccinate compared to those who were not working. The primary reasons for vaccine hesitancy were concerns with side effects and not believing in vaccines, which should be considered during educational strategies prior to dengue vaccine implementation. In general, dengue vaccine intention is high in PR and has increased after COVID-19 vaccine availability, potentially due to increased awareness of vaccine importance during the COVID-19 pandemic.

World Dengue Day: A call for action.

Commemorating the 2021 ASEAN Dengue Day and advocacy for World Dengue Day, the International Society for Neglected Tropical Diseases (ISNTD) and Asian Dengue Voice and Action (ADVA) Group jointly hosted the ISNTD-ADVA World Dengue Day Forum-Cross Sector Synergies in June 2021. The forum aimed to achieve international and multisectoral coordination to consolidate global dengue control and prevention efforts, share best practices and resources, and improve global preparedness. The forum featured experts around the world who shared their insight, research experience, and strategies to tackle the growing threat of dengue. Over 2,000 healthcare care professionals, researchers, epidemiologists, and policy makers from 59 countries attended the forum, highlighting the urgency for integrated, multisectoral collaboration between health, environment, education, and policy to continue the march against dengue. Sustained vector control, environmental management, surveillance improved case management, continuous vaccine advocacy and research, capacity building, political commitment, and community engagement are crucial components of dengue control. A coordinated strategy based on science, transparency, timely and credible communication, and understanding of human behavior is needed to overcome vaccine hesitancy, a major health risk further magnified by the COVID-19 pandemic. The forum announced a strong call to action to establish World Dengue Day to improve global awareness, share best practices, and prioritize preparedness in the fight against dengue.

Changing epidemiology of dengue fever in children in South America.

PURPOSE OF REVIEW: Dengue is the most important arthropod-borne viral disease of public health significance. Its geographic distribution includes 128 countries worldwide, affecting 390 million people every year causing significant morbidity and mortality in children and adults everywhere. RECENT FINDINGS: In the past, severe dengue affected mostly adults in the Americas; this scenario has changed and now cases of dengue, severe dengue, and dengue deaths have increased in children under 15 years in Brazil and in Colombia. Dengue and COVID-19 co-infections have been reported in South America, with increased hospitalization. A dengue vaccine for 9-year-old children and older children and adults who have serological evidence of previous dengue has been licensed in many countries; a different dengue vaccine trial for 4-16-year-old children has demonstrated decrease in clinical dengue and decrease in dengue hospitalizations. SUMMARY: There is no specific treatment of dengue, and a changing climate, insecticide resistance and urban expansion have permitted the vector's spread, making the vector control almost impossible. The hope for dengue control relies on vaccine development; there is important research on this area with one vaccine already licensed and another one showing promising results.

Assessing the efficacy of male Wolbachia-infected mosquito deployments to reduce dengue incidence in Singapore: study protocol for a cluster-randomized controlled trial.

BACKGROUND: Dengue is a severe environmental public health challenge in tropical and subtropical regions. In Singapore, decreasing seroprevalence and herd immunity due to successful vector control has paradoxically led to increased transmission potential of the dengue virus. We have previously demonstrated that incompatible insect technique coupled with sterile insect technique (IIT-SIT), which involves the release of X-ray-irradiated male Wolbachia-infected mosquitoes, reduced the Aedes aegypti population by 98% and dengue incidence by 88%. This novel vector control tool is expected to be able to complement current vector control to mitigate the increasing threat of dengue on a larger scale. We propose a multi-site protocol to study the efficacy of IIT-SIT at reducing dengue incidence. METHODS/DESIGN: The study is designed as a parallel, two-arm, non-blinded cluster-randomized (CR) controlled trial to be conducted in high-rise public housing estates in Singapore, an equatorial city-state. The aim is to determine whether large-scale deployment of male Wolbachia-infected Ae. aegypti mosquitoes can significantly reduce dengue incidence in intervention clusters. We will use the CR design, with the study area comprising 15 clusters with a total area of 10.9 km2, covering approximately 722,204 residents in 1713 apartment blocks. Eight clusters will be randomly selected to receive the intervention, while the other seven will serve as non-intervention clusters. Intervention efficacy will be estimated through two primary endpoints: (1) odds ratio of Wolbachia exposure distribution (i.e., probability of living in an intervention cluster) among laboratory-confirmed reported dengue cases compared to test-negative controls and (2) laboratory-confirmed reported dengue counts normalized by population size in intervention versus non-intervention clusters. DISCUSSION: This study will provide evidence from a multi-site, randomized controlled trial for the efficacy of IIT-SIT in reducing dengue incidence. The trial will provide valuable information to estimate intervention efficacy for this novel vector control approach and guide plans for integration into national vector control programs in dengue-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT05505682 . Registered on 16 August 2022. Retrospectively registered.

Risk Factors Associated with Passengers with Imported Dengue Fever at International Airports in Taiwan.

Dengue fever (DF) is a mosquito-borne disease prevalent in the tropics (e.g., sub-Saharan Africa, Asia, and Central and South America) and a common cause of febrile illness in travelers. The high incidence of imported DF in Taiwan has led to a domestic outbreak. This study explored the risk factors associated with individuals given diagnoses of imported DF at international airports in Taiwan. The results may serve as a reference for DF prevention. In this retrospective study, data from the symptom notification system database of the Taiwan Centers for Disease Control (TCDC) were used. These data concerned travelers who returned to Taiwan from DF-endemic areas with suspected DF symptoms. The epidemiological characteristics of the cases were analyzed, and 28 variables related to DF infection were included in the multivariate logistic regression analysis. In 2018-2019, there were 8656 cases (451 positive and 8205 negative cases). The results revealed DF symptoms and a 16-30-day stay in endemic areas to be independent risk factors and the presence of three respiratory symptoms and <10 days of short-term travel to be protective factors. These results may enable the accurate assessment of symptoms in travelers with DF as well as the risk factors associated with imported DF, lowering the risk of indigenous DF outbreaks caused by imported DF.

Does COVID-19 lockdowns have impacted on global dengue burden? A special focus to India.

BACKGROUND: The world has been battling several vector-borne diseases since time immemorial. Socio-economic marginality, precipitation variations and human behavioral attributes play a major role in the proliferation of these diseases. Lockdown and social distancing have affected social behavioral aspects of human life and somehow impact on the spread of vector borne diseases. This article sheds light into the relationship between COVID-19 lockdown and global dengue burden with special focus on India. It also focuses on the interconnection of the COVID-19 pandemic (waves 1 and 2) and the alteration of human behavioral patterns in dengue cases. METHODS: We performed a systematic search using various resources from different platforms and websites, such as Medline; Pubmed; PAHO; WHO; CDC; ECDC; Epidemiology Unit Ministry of Health (Sri Lanka Government); NASA; NVBDCP from 2015 until 2021. We have included many factors, such as different geographical conditions (tropical climate, semitropic and arid conditions); GDP rate (developed nations, developing nations, and underdeveloped nations). We also categorized our data in order to conform to COVID-19 duration from 2019 to 2021. Data was extracted for the complete duration of 10 years (2012 to 2021) from various countries with different geographical region (arid region, semitropic/semiarid region and tropical region). RESULTS: There was a noticeable reduction in dengue cases in underdeveloped (70-85%), developing (50-90%), and developed nations (75%) in the years 2019 and 2021. The dengue cases drastically reduced by 55-65% with the advent of COVID-19 s wave in the year 2021 across the globe. CONCLUSIONS: At present, we can conclude that COVID-19 and dengue show an inverse relationship. These preliminary, data-based observations should guide clinical practice until more data are made public and basis for further medical research.

Effects of COVID-19 Non-Pharmacological Interventions on Dengue Infection: A Systematic Review and Meta-Analysis.

Non-pharmacological interventions (NPIs) implemented during the coronavirus disease 2019 (COVID-19) pandemic have demonstrated significant positive effects on other communicable diseases. Nevertheless, the response for dengue fever has been mixed. To illustrate the real implications of NPIs on dengue transmission and to determine the effective measures for preventing and controlling dengue, we performed a systematic review and meta-analysis of the available global data to summarize the effects comprehensively. We searched Embase, PubMed, and Web of Science in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines from December 31, 2019, to March 30, 2022, for studies of NPI efficacy on dengue infection. We obtained the annual reported dengue cases from highly dengue-endemic countries in 2015-2021 from the European Centre for Disease Prevention and Control to determine the actual change in dengue cases in 2020 and 2021, respectively. A random-effects estimate of the pooled odds was generated with the Mantel-Haenszel method. Between-study heterogeneity was assessed using the inconsistency index (I2 ) and subgroup analysis according to country (dengue-endemic or non-endemic) was conducted. This review was registered with PROSPERO (CRD42021291487). A total of 17 articles covering 32 countries or regions were included in the review. Meta-analysis estimated a pooled relative risk of 0.39 (95% CI: 0.28-0.55), and subgroup revealed 0.06 (95% CI: 0.02-0.25) and 0.55 (95% CI: 0.44-0.68) in dengue non-endemic areas and dengue-endemic countries, respectively, in 2020. The majority of highly dengue-endemic countries in Asia and Americas reported 0-100% reductions in dengue cases in 2020 compared to previous years, while some countries (4/20) reported a dramatic increase, resulting in an overall increase of 11%. In contrast, there was an obvious reduction in dengue cases in 2021 in almost all countries (18/20) studied, with an overall 40% reduction rate. The overall effectiveness of NPIs on dengue varied with region and time due to multiple factors, but most countries reported significant reductions. Travel-related interventions demonstrated great effectiveness for reducing imported cases of dengue fever. Internal movement restrictions of constantly varying intensity and range are more likely to mitigate the entire level of dengue transmission by reducing the spread of dengue fever between regions within a country, which is useful for developing a more comprehensive and sustainable strategy for preventing and controlling dengue fever in the future.

Treatment-Seeking Behaviors and Knowledge, Attitude and Practices among Suspected Dengue Adult Patients at the Hospital for Tropical Diseases, Bangkok, Thailand.

Dengue infection is a major public health problem in Thailand with an increasing incidence in the adult population. Patients' knowledge, attitude and practices (KAP) with regarding dengue infection have direct influences on treatment-seeking behaviors and clinical outcomes. We conducted a cross-sectional study to assess the KAP and treatment-seeking behaviors of suspected dengue adult patients attending the Hospital for Tropical Diseases (HTD) in Bangkok, from March 2014 to February 2015. Among 167 participants, the majority of participants (87.9%) were unaware of dengue infection and most of them reported initial self-medication (95.2%). The mean days of fever before attending to the HTD was 4.9 ± 1.7 days. Outpatient cases reported seeking care significantly earlier than inpatient cases (mean: 3.1 days vs. 5.0 days; p < 0.001). The majority of patients believed that dengue infection has a high mortality rate (63%) and must be treated in hospital (91.3%), highlighting the lack of understanding and misperceptions regarding dengue-related knowledge in the general population. Patients who reported recent or current dengue infection in their family or neighborhood sought medical care early and reported good preventive practices. Health education should focus on the adult population to improve awareness of dengue symptoms and promote early treatment-seeking behavior.

Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9-50 years: a randomised, controlled, phase 2, non-inferiority study.

BACKGROUND: Dengue is endemic in many countries throughout the tropics and subtropics, and the disease causes substantial morbidity and health-care burdens in these regions. We previously compared antibody responses after one-dose, two-dose, or three-dose primary regimens with the only approved dengue vaccine CYD-TDV (Dengvaxia; Sanofi Pasteur, Lyon, France) in individuals aged 9 years and older with previous dengue exposure. In this study, we assessed the need for a CYD-TDV booster after these primary vaccination regimens. METHODS: In this randomised, controlled, phase 2, non-inferiority study, healthy individuals aged 9-50 years recruited from three sites in Colombia and three sites in the Philippines (excluding those with the usual contraindications to vaccinations) were randomly assigned 1:1:1 via a permuted block method with stratification by site and by age group using an independent voice response system to receive, at 6-month intervals, three doses of CYD-TDV (three-dose group), one dose of placebo followed by two doses of CYD-TDV (two-dose group), or two doses of placebo followed by one dose of CYD-TDV (one-dose group). Participants were also randomly assigned (1:1) to receive a CYD-TDV booster at 1 year or 2 years after the last primary dose. Each CYD-TDV dose was 0·5 mL and administered subcutaneously in the deltoid region of the upper arm. The investigators and sponsor, study staff interacting with the investigators, and participants and their parents or legally acceptable representatives were masked to group assignment. Neutralising antibodies were measured by 50% plaque reduction neutralisation testing, and geometric mean titres (GMTs) were calculated. Due to a change in study protocol, only participants who were dengue seropositive at baseline in the Colombian cohort received a booster vaccination. The primary outcome was to show non-inferiority of the booster dose administered at 1 year or 2 years after the two-dose and three-dose primary regimens; non-inferiority was shown if the lower limit of the two-sided adjusted 95% CI of the between-group (day 28 post-booster dose GMT from the three-dose or two-dose group vs day 28 GMT post-dose three of the three-dose primary regimen [three-dose group]) geometric mean ratio (GMR) was higher than 0·5 for each serotype. Non-inferiority of the 1-year or 2-year booster was shown if all four serotypes achieved non-inferiority. Safety was assessed among all participants who received the booster. This trial is registered with ClinicalTrials.gov, NCT02628444, and is closed to accrual. FINDINGS: Between May 2 and Sept 16, 2016, we recruited and enrolled 1050 individuals who received either vaccine or placebo. Of the 350, 348, and 352 individuals randomly assigned to three-dose, two-dose, and one-dose groups, respectively, 108, 115, and 115 from the Colombian cohort were dengue seropositive at baseline and received a booster; 55 and 53 in the three-dose group received a booster after 1 year and 2 years, respectively, as did 59 and 56 in the two-dose group, and 62 and 53 in the one-dose group. After the three-dose primary schedule, non-inferiority was shown for serotypes 2 (GMR 0·746; 95% CI 0·550-1·010) and 3 (1·040; 0·686-1·570) but not serotypes 1 (0·567; 0·399-0·805) and 4 (0·647; 0·434-0·963) for the 1-year booster, and again for serotypes 2 (0·871; 0·673-1·130) and 3 (1·150; 0·887-1·490) but not serotypes 1 (0·688; 0·479-0·989) and 4 (0·655; 0·471-0·911) for the 2-year booster. Similarly, after the two-dose primary schedule, non-inferiority was shown for serotypes 2 (0·809; 0·505-1·300) and 3 (1·19; 0·732-1·940) but not serotypes 1 (0·627; 0·342-1·150) and 4 (0·499; 0·331-0·754) for the 1-year booster, and for serotype 3 (0·911; 0·573-1·450) but not serotypes 1 (0·889; 0·462-1·710), 2 (0·677; 0·402-1·140), and 4 (0·702; 0·447-1·100) for the 2-year booster. Thus, non-inferiority of the 1-year or 2-year booster was not shown after the three-dose or two-dose primary vaccination regimen in dengue-seropositive participants. No safety concerns occurred with the 1-year or 2-year CYD-TDV booster. INTERPRETATION: CYD-TDV booster 1 year or 2 years after the two-dose or three-dose primary vaccination regimen does not elicit a consistent, meaningful booster effect against all dengue serotypes in participants who are seropositive for dengue at baseline. FUNDING: Sanofi Pasteur. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Level of dengue preventive practices and associated factors in a Malaysian residential area during the COVID-19 pandemic: A cross-sectional study.

BACKGROUND: Dengue fever is a mosquito-borne viral infection that is endemic in more than 100 countries and has the highest incidence among infectious diseases in Malaysia. The increase of dengue fever cases during the COVID-19 pandemic and the movement control order (MCO) highlighted the necessity to assess the dengue preventive practices among the population. Thus, this study aimed to determine the level of dengue preventive practices and its associated factors among residents in a residential area in Johor, Malaysia during the COVID-19 pandemic. METHOD: A community-based cross-sectional study was conducted on 303 respondents from a Johor residential area between May and June 2021. A validated self-administered questionnaire was created using google forms and distributed to the respondents via WhatsApp. The questionnaire consisted of three sections: (i) Sociodemographic characteristics and history of dengue fever, (ii) dengue preventive practices, and (iii) six constructs of the Health Belief Model (HBM). The association between the dependent and independent variables were examined using multiple logistic regression with a significant level set at less than 0.05. RESULT: About half of the respondents have a good level of dengue preventive practices. Respondents with a history of dengue fever (aOR = 2.1, 95% CI: 1.1-4.2, p = 0.033), low perceived susceptibility (aOR = 1.8, 95% CI: 1.1-3.0, p = 0.018), high self-efficacy (aOR = 1.7, 95% CI: 1.0-2.8, p = 0.045), and high cues to take action (aOR = 2.5, 95% CI: 1.5-4.2, p < 0.001) had higher odds of practicing good dengue preventive measures. CONCLUSION: This study demonstrated a moderate level of dengue preventive practices during the COVID-19 pandemic. Therefore, a stronger dengue control programme is recommended by focusing on cues to take action, self-efficacy, and recruiting those with a history of dengue fever to assist health authorities in promoting good dengue preventive practices in the community.

COVID-19 lockdown and increased incidence of dengue: A note.

COVID-19 is the important global problem. Lockdown is a general disease control measure against COVID-19. The aim of lockdown is the reduce incidence of COVID-19. From reappraisal on the available data from a tropical endemic country (1), the change of incidences of both COVID-19 and rotavirus infection incidence after lockdown can be seen.

[Dengue amidst COVID-19: challenges & control measures for the double burden].

Dengue, an arbovirus, is a public health treat in the tropics and sub-tropical climates worldwide. The disease incidence has grown dramatically worldwide, with an estimated 390 million dengue virus infection per year. Dengue has distinct epidemiological patterns which are associated with the four virus serotypes. All four serotypes can co-circulate within a region, in which a number of regions are hyperendemic for all 4 serotypes. Currently, there are no specific treatment or vaccine for the disease. Dengue prevention depends on vector control measures and early interventions. The COVID-19 pandemic has placed immense pressure on health care and management systems worldwide. During the COVID-19 pandemic, the situation was aggravated by the simultaneous dengue outbreaks, that has led to a double burden which has further impacted the healthcare sector, particularly in resource limited settings. This review article will focus on dengue epidemics during the COVID-19 pandemic and discuss on recent findings on immunological cascades between dengue and COVID-19 and, the impact on vaccine development.