Dengue on the Rise

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.

 

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