Dengue is the disease caused by 4 closely related but distinct viruses, dengue virus 1–4 (DENV-1–4), referred to as virus types or serotypes. DENV are most commonly transmitted by the bite of an infected female Aedes spp mosquito.
It is the most common arboviral disease worldwide, with an estimated 390 million dengue virus infections and 96 million symptomatic cases annually.1 The global incidence has almost doubled in the last 3 decades and is expected to continue growing in Asia, sub-Saharan Africa and Latin America.
Approximately half of the world’s population now lives in areas that are suitable for dengue transmission.2,3 Historically, the greatest burden of dengue has been on children, adolescents, and young adults.4 In 2019, countries in the Americas reported more than 3 million cases of dengue, the highest number ever recorded,5 with a higher proportion of severe cases of dengue and an increase in mortality in the pediatric population of children aged 5 to 9 years.6
Dengue is increasingly common as an etiology of fever in international travelers7 and has been reported as the main etiology of febrile illness in travelers from some endemic regions during epidemic years.8 In addition to the circulation of the four DENVs throughout the world , surveillance of travelers returning with dengue demonstrated high genetic diversity among circulating DENV genotypes within serotypes, with potential implications for vaccine immunity or escape.9,10
| A growing problem in the United States |
The increasing number of dengue cases in the United States is a public health concern. In parts of the United States and states loosely associated with endemic dengue transmission, including American Samoa, Puerto Rico, U.S. Virgin Islands, Federation of States of Micronesia, Republic of the Marshall Islands, and the Republic of Palau, outbreaks of Dengue fever can be explosive, overwhelming the capacity of the health care system.
In Puerto Rico, the largest U.S. territory where dengue is endemic, the highest incidence of dengue cases and hospitalizations from 2010 to 2020 occurred among children ages 10 to 19.11 For the same period, cases Confirmed dengue cases ranged from a low of 3 cases in 2018 to a high of 10,911 cases in 2010,11 although suspected cases during the outbreak years were considerably higher.12
Although local transmission of dengue does not occur frequently in most states, an increasing number of US travelers13 with dengue have been reported in recent years, with a record 1,475 cases in 2019, more than 50% higher than the previous peak in 2016.14 Viremia among travel-associated dengue cases may also result in focal outbreaks in non-endemic areas, with dengue-competent mosquito vectors present in approximately half of all US counties.15 Dengue cases have been reported in several states in recent years, including 70 cases in Florida in 2020,14 200 cases in Hawaii in 2015,14 and 53 cases in Texas in 2013.16
| Environmental factors contributing to dengue as a threat to public health |
In dengue endemic areas, environmental factors such as stagnant water where mosquitoes lay eggs, poor quality housing, lack of air conditioning, and climatic factors (i.e., temperature, precipitation, and humidity) increase the abundance, distribution, and risk of exposure to Aedes aegypti , the main vector responsible for the transmission of dengue, or other Aedes spp mosquitoes. which can also transmit dengue.2,17–21
Climate change is predicted to continue to increase the population at risk of dengue primarily through increased transmission in currently endemic areas and secondarily through the expansion of the geographic range of Aedes spp. mosquitoes.2,22
Urbanization, increasing population density, human migration, and social and environmental growth factors associated with poverty and forced displacement are also expected to drive the increase in dengue incidence and strength of infection globally. 21:23–26
Travel is an important driver of dengue spread by introducing dengue into non-endemic areas with competent vectors13,23 or by introducing new serotypes into endemic areas where the new serotype did not exist, increasing the risk of antibody-dependent enhancement. (RAD) and severe disease.27,28
The combined environmental effects of poverty and the greater scale and speed of human movement may also increase the risk of dengue.24,29
The combined environmental effects of climate change, urbanization, poverty and human migration together expand the threat of dengue to individuals and public health systems in the future.
| Pathogenesis |
DENVs belong to the genus Flavivirus of the family Flaviviridae . Because there are 4 serotypes of dengue, individuals living in endemic areas can become infected up to 4 times in their lifetime. Although most dengue virus infections are asymptomatic or cause only mild disease, severe disease can occur and is characterized by plasma extravasation, a pathophysiological process by which the protein-rich fluid component of blood leaks into tissue. surrounding area, leading to the accumulation of extravascular fluid resulting in shock, coagulopathy, or target organ impairment.30,31
Infection with 1 dengue serotype induces lifelong protection against symptomatic infection with that specific serotype (homotypic immunity)32,33 and induces only short-term cross-reactive protection of the disease to the other serotypes (heterotypic immunity) during several months to years.34,35
Older children and adults who experience their second dengue infection are at their highest risk for severe illness due to RAD. RAD has also been observed among children; children born to mothers with prior dengue virus infection had the lowest risk for dengue soon after birth and a period of highest risk for severe disease approximately 4 to 12 months after birth. followed by a decreased risk of severe disease from approximately 12 months after birth.36
The initial period of lower risk was correlated with high levels of passively acquired maternal dengue antibodies immediately after birth and the period of higher risk with a decline in these antibodies to subneutralizing levels. After further degradation of these maternal antibodies, there was neither protection against dengue provided by high levels of postnatal antibodies nor increased risk of dengue and severe disease from intermediate levels of antibodies.37
Later work demonstrated that lower titers of heterotypic antibodies are ineffective in neutralizing virions but still bind to them, facilitating binding to Fc ɣ receptors on circulating monocytes, and resulting in greater viremia than in primary infections.38
The feared sequelae of plasma extravasation is thought to be mediated by high levels of DENV nonstructural protein 1 (NS1), a key protein for viral replication and pathogenesis,39,40 which damages endothelial glycocalyces and disrupts cell junctions. endothelial cells.41,42 Cell-mediated immunity through dengue-specific CD8 T cells is thought to protect against RAD and severe disease.43,44
Although RAD occurs in infants due to the interaction between maternal antibodies and primary infection, it is also explanatory of severe disease in older children and adults where the heterotypic antibodies produced after a primary dengue infection will decline over time to subneutralizing levels, resulting in increased risk of severe disease with secondary infection.
Following secondary infection , potent multitype/cross-neutralizing antibodies are induced which then protect against severe disease in tertiary and quaternary infections.45,46 Although the risk of severe dengue is highest with secondary infection, it can also occur in primary infection, tertiary and quaternary, and possibly after Zika virus infection.47,48 Identifying cases of severe dengue and understanding the pathogenesis of disease severity is an active area of research with important implications for future vaccines and interventions.49
| Clinical considerations |
> Presentation and evaluation
DENV infections have a wide range of presentations from asymptomatic infection (approximately 75% of all infections50) to mild to moderate febrile illness to severe illness with associated coagulopathy, shock, or target organ impairment.30,31 Symptomatic infections are They most commonly present with fever accompanied by nonspecific symptoms such as nausea, vomiting, skin rash, myalgia, arthralgia, retro-orbital pain, headache and/or leukopenia.51
Severe disease develops in up to 5% of all dengue patients, although certain populations, such as infants ≤1 year of age, pregnant women, and adults ≥65 years of age, or individuals with specific underlying conditions such as diabetes, class III obesity, hypertension, asthma, coagulopathy, gastritis or peptic ulcer, hemolytic disease, chronic liver disease, anticoagulant therapy, or kidney disease, have an increased risk of severe disease.52,53
In all patients with dengue, warning signs are specific clinical findings that can predict progression to severe disease and are used by the World Health Organization (WHO) to assist physicians in triage and decision management. .
Warning signs of dengue include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, liver enlargement > 2 cm, and increased hematocrit concurrent with rapid decrease in platelet count.52
Although warning signs are useful for the evaluation of patients with a high suspicion of dengue (for example, during an outbreak), they are not intended to differentiate dengue from other infections and non-infectious diseases such as influenza, coronavirus disease 2019, malaria , Zika, measles, leptospirosis, rickettsiosis, typhoid fever, Kawasaki, or idiopathic thrombocytopenic purpura.
Because rapid recognition and early treatment of dengue can greatly reduce morbidity and mortality,54,55 physicians practicing in the United States and other nonendemic areas should keep dengue in the differential diagnosis of diseases. febrile in travelers and in areas with competent mosquito vectors.
> Diagnostic tests for symptomatic DENV infection
For symptomatic dengue patients, nucleic acid amplification tests (NAATs) in serum, plasma or whole blood detect DENV RNA during the first 7 days of illness with high sensitivity and specificity.56,57 Likewise, the NS1 antigen can also be detected within the first 7 days and provides confirmatory evidence of DENV infection.58
For patients with a negative NAAT or patients presenting more than 7 days after symptom onset, a positive immunoblobulin M (IgM) against DENV may suggest recent infection, although with less certainty than a NAAT or NS1 test, because to cross-reactivity with other flaviviruses. In particular, the Zika virus is a flavivirus that has been transmitted in most countries where DENV transmission is present.59
In patients from areas with ongoing transmission of another flavivirus (e.g., Zika virus) and whose only evidence of dengue is a positive anti-DENV IgM test, plaque reduction neutralization tests (PRNT) that quantify antibody titers Specific virus neutralizers can distinguish DENV from other flaviviruses, in some but not all cases.
PRNTs, however, are rarely available in clinical laboratories and typically do not provide results within a time frame that is meaningful to clinicians managing acute illness.
PRNTs may be valuable in circumstances where confirming the diagnosis may have important clinical implications, such as distinguishing a dengue virus infection from a Zika virus infection in an individual pregnant woman or for epidemiological implications for a region, such as distinguishing yellow fever from dengue.60,61
The US Food and Drug Administration (FDA) has approved a NAAT for use in serum and whole blood, an NS1 antigen enzyme-linked immunosorbent assay test in serum, and an enzyme-linked immunosorbent IgM test in serum.56,59,62–64 Other non-FDA approved tests for DENV infection are used in clinical practice and are commercially available from accredited laboratories.
> Treatment
Although several medications were explored as potential therapeutics for dengue, none demonstrated a reduction in viremia, clinical manifestations or complications.30,65
As such, dengue treatment focuses on supportive care. Clinicians should evaluate all patients at presentation and at follow-up for warning signs or other signs and symptoms of severe dengue.
Most patients without warning signs can be treated as outpatients, while patients at high risk of progression to serious illness based on age or underlying conditions, patients with warning signs, or patients with challenging social circumstances should be treated. be evaluated for inpatient observation or management.66
For outpatients, fever can be controlled with acetaminophen and physical cooling measures; Due to the risk of bleeding and thrombocytopenia, aspirin and nonsteroidal anti-inflammatory drugs are not recommended. Early on, abundant oral hydration was associated with lower hospitalization rates in children with dengue and is a key component of outpatient dengue care.67–69
Early recognition of warning signs or severe dengue is essential for prompt initiation of systemic intravenous fluid management to restore intravascular volume and prevent related complications and disease progression.30,70 Large volume resuscitation is recommended. with isotonic solutions for patients in shock.54,71–73
Fluid management in dengue requires continuous clinical and laboratory monitoring and rate adjustment to maintain adequate volume but also to avoid fluid overload. Mortality from untreated severe dengue can be 13% or higher74,75 but can be reduced to <1% with early diagnosis and appropriate management.55
Detailed information on routine fluid management is provided in current guidelines from the WHO, the Pan American Health Organization, and the Centers for Disease Control and Prevention (CDC).72,73,76 Corticosteroids, 77 immunoglobulins,78 and prophylactic platelet transfusions79,80 have not demonstrated benefits in patients with dengue and are not recommended.
> Traditional prevention measures
Dengue prevention involves protection against mosquito bites.
Travelers and residents of endemic areas can prevent mosquito bites by using approved insect repellents and wearing clothing that covers arms and legs.
The use of reinforced windows and doors, air conditioning, and mosquito nets have also been associated with protection from dengue infections.24,81–87 Sites where mosquitoes lay eggs should be eliminated by emptying and cleaning, covering, or eliminating containers of stagnant water around them. of the house.
Mosquito bite prevention measures are important for all people at risk of dengue, including vaccinated children.
> New vector control efforts
Traditional vector control interventions can be time-consuming and inefficient.88 Additionally, chemical control is limited by widespread insecticide resistance in endemic areas.89 In response to these challenges, novel vector control methods have been developed including several strategies employing genetically modified mosquito technology and 2 strategies using Wolbachia pipientis , an intracellular bacteria found in approximately 60% of all insects, but not commonly found in wild Aedes mosquitoes.90–92
The first strategy that Wolbachia uses is Wolbachia- mediated suppression , in which a reduction in wild populations of Aedes mosquitoes is achieved by continually releasing infected males into the environment.93
When infected males mate with wild females, the resulting eggs are nonviable, leading to a population decline in wild mosquito populations.94 Some reports have documented reductions in wild populations that can transmit dengue by more than 80%.95.96
The second strategy is the Wolbachia replacement method , where both male and female mosquitoes infected with Wolbachia are released . Because Wolbachia is transmitted maternally, mosquitoes that hatch from the eggs of infected females will be infected with Wolbachia from birth.97,98 Wolbachia infection in female mosquitoes that feed on blood reduces the transmission of arboviruses, including dengue, chikungunya and Zika. This method has demonstrated significant reductions of almost 80% for dengue infection outcomes and related hospitalizations in areas where it has been implemented99 and is currently being implemented in several countries.
Extensive studies have found no evidence of Wolbachia on plants, soil or other insects in contact with Wolbachia -infected mosquitoes or any evidence of transmission of Wolbachia to humans through the bites of infected mosquitoes, indicating that the safety risks of Wolbachia- based interventions for humans and the environment are low.100
> Current vaccines against dengue
ACIP made the first recommendation of a dengue vaccine (Dengvaxia) for use in the United States on June 24, 2021, marking a historic moment for dengue control after decades of global efforts to develop a safe and effective vaccine. Two other vaccines, TAK-003 developed by Takeda and TV003 developed by the National Institutes of Health, are in late-stage trials with efficacy results published or expected in 2022.
> Principles of live attenuated dengue vaccines
All 3 are live vaccines and contain 4 different attenuated vaccine viruses (tetravalent) directed at each of the dengue virus serotypes with the aim of achieving a balance of protective immunity against the 4 serotypes, both in those that are DENV naïve and in those who have previously been infected with DENV. Vaccine virus replication (infectivity) of each vaccine serotype after immunization will result in antigen stimulation, which then leads to homotypic immunity. Infectivity by vaccine virus serotype differed among the 3 vaccines.
These differences in vaccine serotype-specific infectivity reflected the induction of homotypic neutralizing antibody titers. Dengvaxia induced approximately 70% homotypic antibodies for DENV-4 but <50% for DENV-1, DENV-2 and DENV-3.101 Antibodies induced by TAK-003 were 83% homotypic for DENV-2 and 5%, 12% and 27% homotypic for DENV-1, DENV-3 and DENV-4, respectively.102 TV003 induced a balanced homotypic antibody response to DENV-1 (62%), DENV-2 (76%), DENV-3 (86% ) and DENV-4 (100%).103 Although homotypic antibody titers are associated with serotype-specific vaccine efficacy, immunological correlates that reliably predict vaccine efficacy have not yet been identified and remain unknown. an area of active research.46
| DENGVAXIA |
> History of Dengvaxia
Dengvaxia uses a 3-dose schedule with each dose administered every 6 months (at months 0, 6, and 12). It was developed by the Universities of Washington and St. Louis and Acambis and licensed to Sanofi Pasteur in 2000, entered phase 3 trials in 2010, and was first recommended by the WHO in 2016 for people ages 9 and up. more who live in areas of high endemicity.
Long-term follow-up data (over 5 years) from phase 3 trials and additional analyzes of efficacy outcomes104–107 demonstrated that children with evidence of prior DENV infection were protected from virologically confirmed dengue disease, including severe dengue if they were vaccinated with Dengvaxia. However, the risk of hospitalization for dengue and severe dengue was increased among children without prior dengue infection who were vaccinated with Dengvaxia and had a subsequent dengue infection in the years after vaccination.
In children without prior dengue infection, the vaccine acts as a silent primary dengue infection resulting in a “secondary-type” infection upon their first infection with wild-type DENV and an increased risk of severe RAD disease.108,109 After Based on these findings, the WHO revised its recommendations for vaccination only for children with laboratory-confirmed evidence of past infection.
Following the WHO recommendation, the FDA authorized Dengvaxia in 2019 and in 2021, ACIP recommends the routine use of Dengvaxia for children aged 9 to 16 years with laboratory confirmation of previous DENV infection and who live in areas where dengue is endemic. . Dengvaxia is the first dengue vaccine recommended for use in the United States.
> Safety and effectiveness
For children aged 9 to 16 years with evidence of previous dengue infection, Dengvaxia has an efficacy of around 80% against the outcomes of virologically confirmed symptomatic dengue (VCD) followed more than 25 months, as well as hospitalization for dengue and severe dengue according to as defined by the criteria established by the data monitoring committee of independent trials and followed for 60 months.105,106 Efficacy by serotype reflected its induction of a homotypic immune response101 with maximum protection against DENV-4 (89%), followed by DENV-3 (80%), and lower against DENV-1 (67%) and DENV-2 (67%).106 Protection against mortality could not be reported because there were no dengue-related deaths in the dengue trials. phase 3.
The most frequently reported adverse effects (regardless of dengue serostatus before vaccination) were headache (40%), pain at the injection site (32%), malaise (25%), asthenia (25%). %) and myalgia (29%) (n=1333).108 Serious adverse events (i.e., life-threatening events, hospitalization, disability or permanent damage, and death) within 28 days were rare in vaccinated participants ( 0.6%) and in control participants (0.8%) and were not significantly different. At 6 months, fewer serious adverse events were reported in the vaccine arm (2.8%) than in the control arm (3.2%).108
Children who were seronegative for dengue at the time of vaccination were at increased risk of severe disease in subsequent dengue infections. The risk of dengue-related hospitalization was approximately 1.5 times higher, and the risk of severe dengue was approximately 2.5 times higher among HIV-negative children aged 9 to 16 years who were vaccinated than in control participants over a period of 5 years.106
> Laboratory tests prior to vaccination
The requirement for a laboratory test prior to administration creates a unique challenge for the implementation of Dengvaxia. In areas with ongoing transmission of flaviviruses in addition to dengue, qualifying laboratory tests include a positive result from a NAAT or NS1 test performed during an episode of acute dengue or a positive result from prevaccination screening serological tests with serological evidence of infection. that meet specific performance characteristics. In areas without other flaviviruses of ongoing transmission, a positive dengue IgM test during an acute dengue episode is also considered a qualifying laboratory test.11
Screening prior to vaccination is essential because many DENV infections are asymptomatic or do not lead to medical consultations and tests.
Therefore, a significant proportion of previously infected people who could benefit from the vaccine will be unaware or do not have laboratory documentation of their previous dengue infection.110–113 One of the most challenging aspects in selecting a dengue test prevaccination is to define benchmarks for test performance, as explored by several international working groups.114,115
To reduce the risk of vaccinating someone without prior DENV infection, test specificity is a priority. Although the specificity and sensitivity of the test are independent of seroprevalence, the positive predictive value (PPV) and negative predictive value are dependent on seroprevalence and describe the probability of a true positive if a patient tests positive or the probability of a true negative if a patient tests negative. In areas with moderate or low seroprevalence (e.g., 30%–50%), high test specificity (>98%) is required to achieve a PPV of 90% and therefore reduce the risk of misclassification. of seronegative individuals.
In these settings, near-perfect specificity is preferred at the expense of sensitivity to minimize the risk of vaccinating a misclassified negative individual and subsequently increasing their risk of severe dengue. However, high prevalence areas (e.g., >60%) benefit from higher test sensitivity and more moderate specificity (e.g., 95%), which would increase identification of children. who benefit from the vaccine.116
Because dengue seroprevalence at ages 9 to 16 years is estimated to be approximately 50% in Puerto Rico117,118 (where the majority of the Dengvaxia-eligible population in the United States and its territories and freely associated states reside) , the CDC recommends that tests have a minimum sensitivity of 75% and a minimum specificity of 98%.
The recommendations also specify that test performance in the population should achieve a PPV ≥90% and a negative predictive value ≥75%.11 These test characteristics were used to model the risks and benefits of implementing Dengvaxia. Using the population of Puerto Rico and an estimated seroprevalence of 50%, the model found that vaccination with Dengvaxia would prevent approximately 4,148 symptomatic cases of disease and 2,956 hospitalizations over a 10-year period. This implementation would also lead to an additional 51 hospitalizations caused by vaccination of people without prior dengue infection who were misclassified by the screening test.119 The most common cause of hospitalization among vaccinated children will be a disease outbreak because the vaccine does not It is 100% effective.
| TAK-003 |
TAK-003, developed by Takeda, consists of 2 doses administered 3 months apart. The clinical trial population was primarily composed of children aged 4 to 16 years. At 18 months after vaccination, vaccine efficacy was found to be 80.2% against DVC, which decreased to 62.0% by 3 years after vaccination.120,121
Efficacy against dengue hospitalization remained higher, at 83.6%, 3 years after vaccination. Differences in efficacy were observed by history of prior dengue infection, with greater efficacy among people with prior infection compared to those without prior infection (65.0%-54.3%), and by age, with greater efficacy in older children.
In contrast to the Dengvaxia findings at 25 months, children who were seronegative at the time of TAK-003 vaccination did not show an increased risk of hospitalization and severe disease compared to the placebo group at 3 years, although Efficacy varied according to DENV serotype and they could not rule out an age effect.106,120
Efficacy against DVC and hospitalization varied by serotype and corresponded to homotypic antibody titers, 102 with the highest efficacy against DENV-2 and the lowest against DENV-3 and DENV-4. Among children without prior DENV infection, no efficacy was observed for DVC against DENV-3 or DENV-4. In the safety analysis, the number of serious adverse events was similar between the vaccinated (2.9%) and placebo (3.5%) groups.
In March 2021, Takeda submitted TAK-003 to the European Medicines Agency for the prevention of dengue of any DENV serotype among people aged 4 to 60 years.122 The company will also make submissions to regulatory agencies in Argentina, Brazil, Colombia, Indonesia, Malaysia, Mexico, Singapore, Sri Lanka and Thailand during 2021 and has future plans to submit to the FDA.
| TV003 |
TV003 was developed by the National Institutes of Health and was formulated by selecting serotype-specific components that were determined to provide the most balanced safety and immunogenicity profile based on an evaluation of multiple monovalent and tetravalent candidates.123,124 Because antibody titers failed to predict the efficacy of Dengvaxia, a human infection model was developed to evaluate the protective immunity induced by TV003 against DENV-2 challenge.
Forty-eight volunteers were enrolled and randomized to receive TV003 (24) or placebo (24). Six months later, volunteers were administered a naturally attenuated DENV-2 challenge virus.125 The primary efficacy endpoint was protection against detectable viremia after challenge.
After challenge, DENV-2 was recovered by culture or reverse transcriptase polymerase chain reaction (RT-PCR) from 100% of placebo recipients (n = 20) and 0% of TV003 recipient (n = 21) (p < 0.0001). Post-challenge, rash was observed in 80% of patients receiving placebo compared to 0% of those receiving TV003 (p < 0.0001).
TV003 has been licensed to several manufacturers globally, including Merck & Co in the United States and the Butantan Institute in Brazil. Phase 3 trials in Brazil are underway with efficacy and safety results expected in late 2022 (Clinical Trial Registration: NCT02406729).
| Conclusion and future directions |
Dengue is the most common arboviral disease worldwide and is projected to increase in global range and burden.
Although advances in the field have progressed gradually for decades, the recent approval of Dengvaxia for routine use marks a major step forward for control and prevention efforts in the United States and paves the way for future dengue vaccines.
Dengvaxia has several complexities that require future research, including the possibility of fewer doses in the initial schedule followed by booster doses years later.30 Because it is the first vaccine to require laboratory testing before administration, public-public alliances Private companies to develop more specific, sensitive, and accessible tests or algorithms will be key to minimizing vaccination of people without prior DENV infection and maximizing the benefit for those with prior infection.
Jurisdictions wishing to use Dengvaxia will need to collect seroprevalence data and ensure that pre-vaccination screening tests meet requirements for positive and negative predictive values. Additionally, behavioral science evaluations to elicit community-level perceptions and concerns combined with health systems research on optimal “test and vaccinate” strategies will result in dengue vaccination programs that are well accepted. , efficient and tailored to individual communities.
TAK-003 and TV003 are in late-stage testing and could soon be approaching licensing. An indication for use in travelers would offer physicians in non-endemic areas of the United States a prophylactic therapeutic option for their patients. While awaiting approval of a vaccine with balanced serotype immunity, a mix-and-match strategy guided by differences in dominant serotype immune responses in each vaccine (TAK-003 followed by Dengvaxia, for example) could potentially lead to higher levels of protection against dengue, but has not yet been evaluated for safety and efficacy in clinical trials.126 For all 3 vaccines, studies evaluating efficacy against emerging variants of the DENV serotype will be important to evaluate the long-term protection induced by the strains vaccinations.10,127
Future dengue vaccines could also benefit from lessons learned from the COVID-19 pandemic, namely that new vaccine platform technologies plus political will can result in rapid development of safe and effective vaccines and that clear communication with the public is crucial to the success of vaccine rollout.128–130 Dengue vaccines based on an mRNA platform are already under investigation.131
Vaccines are a powerful new tool in our arsenal against dengue, but they are just one of many interventions, including novel vector control strategies, to control a virus with a complex epidemiology, immunopathogenesis and clinical picture influenced by change. climate, urbanization, poverty and human migration. Clinicians must remain vigilant in recognizing and diagnosing patients with dengue, because early treatment remains the cornerstone of reducing morbidity and mortality. However, with the recent approval of Dengvaxia, we are one step closer on the path to dengue elimination and can expect exciting new developments in dengue interventions in the near term.
| Comment |
Dengue is a global public health problem since it affects both recognized endemic areas and others that are not but that present cases due to continuous travel and migration.
Health workers must keep in mind the diagnosis of dengue in order to institute early treatment, recognize clinical warning signs, and make recommendations about future infections. On the other hand, this work highlights that the available strategies are promising, both the new interventions at the level of dengue virus vectors, as well as the approved vaccine and those under investigation.
