Thus far, 2019 has been a year marked by several dengue epidemics, from Latin America to Southeast Asia. Data from the Pan American Health Organization (PAHO) indicate about 236,372 total possible cases, with nearly 80,000 laboratory-confirmed cases and 68 deaths this year in the Americas alone. The current total 2019 cases for the region is estimated to already be 42% of the total 2018 cases (561,233 cases), indicating that 2019 totals may potentially surpass those of 2018. This week, Outbreak Observatory explores dengue epidemiology and several challenging factors that are limiting our ability to control this disease.
Current Outbreaks of Dengue
There are a number of concerning dengue epidemics currently ongoing around the world. Médecins Sans Frontières (MSF) recently reported that an outbreak in Honduras has resulted in nearly 800 cases of severe dengue in 2019, more than 80% of which are children 15 years old or younger. Approximately 95% of these cases were reported from a single region in the country (Cortes). Jamaica has also reported increases in dengue cases in 2018 and 2019. There were an estimated 986 total dengue cases in 2018, which was more than four times the yearly total in 2017 (215 total cases). During both December 2018 and January 2019, the number of reported cases exceeded the epidemic threshold for those months. To address the rise in cases, the Jamaican Ministry of Health established an Emergency Operations Center on December 27, 2018 and declared a dengue outbreak on January 3, 2019. Currently, according to PAHO estimates, there were a total of 981 cases reported in the first 5 weeks of 2019 in Jamaica.
In the Pacific Islands and Asia, cases have substantially risen as well. For the first time in a decade, the Cook Islands declared a dengue outbreak. Additionally, the Philippines reported an estimated 40,614 total cases so far in 2019 (through March 2). Nationally, dengue incidence has increased 68% over estimates for the same time period in 2018, and incidence in some areas, such as Zamboanga City, has increased more than 200% compared to 2018. Similarly, the 2018 total (3,135 cases) in Ahmedabad, India, was nearly 5 times what it was in 2014 (638 cases). Interestingly, this increase occurred despite a reported reduction in mosquito density; however, improved surveillance efforts could be contributing to the increase in reported cases.
Characterized by flu-like symptoms including high fever, headache, joint pain, and rash, dengue is spread by bites from Aedes aegypti and Aedes albopictus mosquitoes. While other diseases including Zika and chikungunya are also spread Aedes aegypti, dengue is considered the fastest-spreading vector-borne viral disease worldwide. Generally, symptoms begin within a week of infection and can last between 3 and 10 days. Infections can sometimes cause potentially lethal complications, including dengue hemorrhagic fever and dengue shock syndrome. Dengue fever can be caused by dengue viral serotypes 1-4, but infection with one serotype does not provide any immunity against infections caused by other serotypes. In fact, subsequent infections are actually associated with an increased risk of developing severe dengue disease. This key detail is important to note when discussing challenges facing dengue control programs.
Compared to just 9 countries reporting severe dengue epidemics prior to 1970, dengue is endemic today in more than 100 countries globally. Consequently, nearly half of the world’s population is at risk of infection. The incidence of the disease has increased in the past few decades, and disease burden is likely underestimated because cases may be underreported or misdiagnosed as other illnesses. Additionally, of the 284-528 million people per year estimated to have dengue infections globally, only a small fraction, approximately 67-136 million, exhibit clinical symptoms of infection.
Dengue is endemic primarily in urban and semi-urban tropical or subtropical regions of the world. Dengue epidemics tend to have seasonal patterns, with transmission often peaking or increasing during rainy seasons, such as what has been observed in Honduras. Periodic epidemics in certain regions can also occur, based on mosquito population levels and local immunity or susceptibility to circulating serotypes. Ambient air temperatures, precipitation, and humidity all affect the geographic distribution, reproduction, and feeding patterns of mosquito populations, as well as the dengue virus incubation period. The longer-term global increase in the number of dengue-affected countries and in dengue incidence over the past several decades could be affected by climate change, population growth, urbanization, increased travel, and poor implementation of effective control measures. This interplay of factors has contributed to the expansion of countries or regions that either did not previously have dengue or have not experienced outbreaks in recent years (decades in some cases), including the US. Interestingly, the WHO reported significant reductions in reported dengue cases in the Americas in 2017, with only 3 countries in the region (Panama, Peru, and Aruba) reporting increases in cases that year, making the recent 2019 reports of cases even more concerning.
Control Measures and Challenges
Aedes mosquitoes are highly resilient and can adapt well to different environments, making it difficult to control vector populations and interrupt transmission. Female mosquitoes can lay thousands of eggs in many different types of places, from water containers to septic tanks and toilets. Additionally, eggs can survive without water for months, so even if control measures were able to remove all larvae, pupae, and adult mosquitoes in a particular location, the population could quickly re-emerge once dessicated eggs remaining in the environment are exposed to water. Meta-analyses conducted by the Special Programme for Research and Training in Tropical Diseases (TDR) have assessed interventions aimed at controlling dengue transmission. Placing screens on windows and doors has been shown to be a popular and effective in impacting dengue transmission. Other interventions such as indoor residual house spraying have also been explored and found to be efficient in standalone studies, but there is unclear evidence that those particular interventions can significantly reduce disease transmission based on results from a meta-analysis conducted on such interventions.
Laboratory diagnosis of dengue is important both for optimizing patient treatment and surveillance efforts. Diagnosis utilizes techniques such as PCR to detect viral components or antigens or serological tests that indicate presence of an immune response. Testing needs to be performed in the first week of illness because viremia and certain antigens are only present during that time period. These timing constraints make laboratory confirmation of cases particularly difficult for lower-income countries that do not have robust a public health and laboratory infrastructure. Syndromic surveillance is also an important method of monitoring dengue transmission. For example, TDR developed an Early Warning and Response System (EWARS) to support dengue surveillance as well as an associated surveillance dashboard and operational guidance for use in countries where dengue is endemic.
A vaccine against dengue has been developed; however, uncertainty remains regarding how to optimally employ the vaccine, due to unique epidemiology characteristics of the vaccine and disease. Dengvaxia is a live recombinant vaccine, developed by Sanofi Pasteur, designed to be effective against all four dengue serotypes, and it is currently licensed in 20 countries. Interestingly, the safety and efficacy of the vaccine depends on whether an individual has been previously exposed to dengue. Specifically, the vaccine tends to be more effective in individuals that have been previously exposed to dengue (seropositive) compared to those who have not (seronegative). The data also indicate individuals who are seropositive at the time of vaccination are at an increased risk of severe dengue disease and hospitalization during future dengue infections. This phenomenon is hypothesized to result from the vaccine mimicking primary dengue infection in the body, which increases the risk of severe complications during natural dengue infections, similar to the elevated risk observed among individuals that experience natural primary and secondary infection.
In light of this emerging evidence, in particular the occurrence of longer-term safety issues among seronegative vaccine recipients, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) revised its dengue vaccination recommendations in 2018. SAGE provides specific guidance for dengue screening, including for low-resource areas that cannot perform more complex diagnostic tests, in order to ensure that only those individuals who have been previously exposed to dengue receive the vaccine. Individuals determined to be seronegative should not be vaccinated due to the reduced efficacy of the vaccine and the increased risk of severe disease. In high-priority areas where dengue is endemic, this is less likely to be an issue, because there is a high probability that most individuals will have already been exposed.
Once a disease that appeared to affect only 9 countries just a few decades ago, dengue is now endemic in areas that affect nearly half the global population. The longer-term global rise in dengue incidence, along with the increased occurrence of localized outbreaks—despite the availability of a vaccine—highlights the challenge facing dengue control efforts worldwide. Mitigating the global burden of dengue faces a number of barriers, including the ability of Aedes mosquito populations to flourish in spite of various control measures, difficulties in detecting and diagnosing dengue cases, and the unique epidemiological characteristics that limit the efficacy of available vaccines. Continued dedication to surveillance efforts, particularly syndromic surveillance, and advanced research and development for more effective vaccines could fill existing gaps that currently limit the ability to control the spread of this disease.
Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly to allow others to learn from these experiences in order to improve global outbreak response capabilities.
Photo courtesy of CDC/ James Gathany