Dengue Fever: Mogadishu to Marseille

Richard Allan, 3rd February 2023  https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(22)00454-5/fulltext

A mosquito and a disease – which, until a decade ago, were considered largely an Asian and Latin American problem – have moved into the centre stage as the post-Covid world looks more earnestly at how to be ready for and prevent the next global disease threat.

Dengue virus is transmitted not by human contact, but by the discreet bite of a tiny Aedes mosquito. There are more than 3000 species of mosquitoes on earth, and female mosquitoes need to feed on animal or human blood for successful egg development.  Not all mosquito species can act as disease vectors, but at least 88 species can. This includes 10 or more Aedes species, which transmit major flaviviruses such as dengue, chikungunya, yellow fever and Zika, depending on where you are in the world.

The pathogens carried and transmitted when mosquitos feed on human blood have an intimate relationship with both the mosquito and the human, living part of their life cycle in each of these, needing to go through early development stages within the mosquito before becoming infective to humans, when transmitted in the saliva of the feeding insect.

Both the dengue virus and its vector mosquito species are highly efficient and adaptable, and both have spread across the globe within my lifetime. Since dengue was first discovered and identified in the 1960s, in just 9 countries in Asia and Latin America, it has spread to 129 countries and all continents. The disease follows quickly in the path of the Aedes mosquito. Two Aedes species are responsible for most dengue transmission, Aedes aegypti and Aedes albopictus. Both species have established themselves fully in Asia, Latin America, the Middle East and Africa, but Aedes Albopictus has proven uniquely adaptable to the more seasonal and cooler climates of Europe too. Since it first arrived in Albania  1979, it has spread to over 20 countries across Europe, and is now also found in southern England. Why? Because its preferred egg laying sites are the very pools of containerised water that we create as a result of humans living together in urban settings, for water features, plant pots, rainwater collection barrels, buckets and old tyres, discarded plastic bottles and cans, open rainwater drains, animal drinking troughs and many, many, more.

Whilst disease surveillance for dengue in Europe is still in its early stage, France reported 9 outbreaks in 2022, with 65 autochthonous dengue cases. https://www.ecdc.europa.eu/en/dengue-monthly

If 65 cases does not sound worrying, consider this, in under 60 years, having spread to 129 countries, cases have risen exponentially, resulting in a total of 3,766,153 clinical cases being identified and reported by the health systems in those countries in 2022. For every person sick with dengue fever, several others will have been infected and will not have developed significant disease symptoms, adding many millions more to the pool of infection when they in turn are bitten by mosquitoes not yet infected. Many more cases seeking treatment will simply be misdiagnosed as fevers of unknown origin, due to the lack of sensitive and accurate diagnostic tools. Currently, dengue diagnosis is largely limited to clinical diagnosis, with confirmatory diagnosis being limited to the few with access to facilities with higher-level laboratories that have blood and serum analysis capacity.

The expansion of Aedes mosquitoes and dengue virus has been largely ignored by the world, as a disease that killed few, was poorly understood and for many, considered to be “not our problem”. The result of ignoring it, is that today, dengue is the fastest-growing vector-borne disease on earth, and it has become a problem on our doorstep too.

There is currently no usable vaccine against dengue, and vaccine development programs of the last decade have been severely set back by unforeseen technical challenges. Those setbacks, make it unlikely that any effective vaccine candidates will become available in the coming decade. In the gap that forms, dengue will spread to many more countries and deeper across all countries.

There is currently no cure for dengue, and whilst the symptoms of uncomplicated dengue cases are largely manageable with a week or so in hospital care, space and resources in many countries’ health systems are already stretched, and still trying to recover from the Covid pandemic.

Sadly, the dengue virus has an even uglier side to it. There are four dengue serotypes (DENV-1, DENV-2, DENV-3 and DENV-4), and all or any of these can cause dengue fever. Once countries have three or more of these serotypes in circulation though, and people become infected on a repeat basis, and their immune systems experience different serotypes, then the risks ramp up dramatically. Subsequent infections with dengue may result in dengue haemorrhagic disease. Patients with this serious form of disease may bleed seriously from their mucous membranes, experience a sudden drop in blood pressure (shock) and up to 20% of these cases will die.

With vaccines at least a decade or more away, we urgently need more effective control of Aedes mosquitoes, and easy-to-use and highly-accurate rapid diagnostic tests (RDT).  RDTs will be essential to improving disease surveillance capacity across countries where aedes vectors have already been identified, and for individual patient diagnosis. The earlier patients are diagnosed and receive medical supportive care, the better their chances of recovery will be, and the strain on countries’ healthcare systems will be more manageable.