by Mechas
Dengue fever is an acute and rapidly spreading disease caused by the dengue virus (DENV) that is transmitted by mosquitos of the Aedes species. In 2019 it was ranked one of the top 10 threats to global health by the World Health Organization (WHO). Yet, being restricted mainly to tropical and subtropical regions, it is often disregarded. However, concern about the spread of dengue is growing, prompting the WHO to establish a Global Dengue Dashboard for global surveillance and monitoring of disease incidence and trends.
Dengue infects more than 100 million people and kills approximately 40,000 individuals each year. However, we still lack effective therapeutic agents and the available vaccines provide only limited protection. The result is a worrisome spike in cases these past years and an increased risk in areas of the world previously unaffected. Dengue is now spreading north and south from equatorial regions due to increased travel, urbanization, and climate change, which also affects the distribution of the Aedes mosquito vector.
Fig. 1. Cross section of a dengue virus showing structural components. Source. Frontispiece: Transmission electron micrograph of dengue virus particles (red). Micrograph courtesy of CDC; colorization and visual effects by NIAID. Credit: CDC and NIAID. Source
DENV is a positive-sense single-stranded RNA virus of the Flavivirus family, which also includes other mosquito-transmitted viruses like yellow fever and West Nile viruses. The 11 kb genome of DENV codes for structural and non-structural proteins required for replication and for making up the mature virion (Fig. 1). These viral particles are transmitted to humans when infected Aedes mosquitos bite and feed on human blood. Given that there are four different DENV serotypes, infection can occur multiple times.
In most cases, an infected individual remains asymptomatic as the immune system successfully controls viral replication. Only a small proportion of individuals develop a flu-like fever for the first 2-3 days. The symptoms can escalate in the following days and produce joint pain and headaches. A small percentage of these patients develop inflammation and vascular damage, resulting in low blood pressure, multi-organ failure, and increased risk of death.
Fig. 2. Color print of the mosquito Aedes aegypti (then called Stegomyia fasciata, today also Stegomyia aegypti). To the left, the male, in the middle and on the right, the female. Above left, a flying pair in copula. Source
What is needed to curb the rising number of dengue infections? One current strategy seeks to reduce dengue transmission by Aedes mosquitos. Although mosquitos are fascinating, they are also the deadliest of all animals. As explained in a previous post, the release of Ae. aegypti mosquitoes (Fig. 2) infected with a Wolbachia bacterium (wMel strain) is used to limit transmission and reduce the incidence of dengue. Additional efforts focus on reducing insect numbers by removing containers that hold standing water where mosquitos breed, like discarded plastic containers, buckets, and tires. Infections are also prevented using appropriate clothing and repellents to prevent mosquito bites.
A recent study by Vuong and collaborators from Vietnam, the United Kingdom, the United States, Germany, and Australia provides important insights regarding the infectious process. The authors looked at the kinetics of viremia, which refers to viruses in the blood. They analyzed a dataset of more than two thousand individuals from Vietnam with symptomatic dengue to understand how viremia impacts patient outcome and disease severity. In most cases, viremia declined rapidly following the onset of symptoms. However, high viral levels correlated with reduced platelet counts and severe clinical outcomes, indicating that viremia during the early phase of the disease serves as a predictor of patient outcome. Thus, they suggest that viremia be used to inform clinical practice and to guide the discovery of drugs that reduce the risk of severe dengue by lowering viral load.
Dengue illustrates the difficulty involved in controlling tropical diseases. It results from the convergence of multiple factors, human, environmental, geographic, and specific pathogen traits. While there have been great advances in knowledge of DENV and the disease, control will require more effective vaccines and therapeutics, as well as sensitive, rapid, and cost-effective diagnostics that distinguish among serotypes and allow timely treatment. In the meantime, we would do well to heed expert advice and take precautions to prevent infection. After all, who knows when dengue might be coming to a place near you.
Do you want to comment on this post? We would be happy about it! Please comment on Mastodon, Bluesky, or on 𝕏 (formerly Twitter).
Comments