Chikungunya virus pathogenesis: From bedside to bench

Abstract

Chikungunya virus (CHIKV) is an arbovirus transmitted to humans by mosquito bite. A decade ago, the virus caused a major outbreak in the islands of the Indian Ocean, then reached India and Southeast Asia. More recently, CHIKV has emerged in the Americas, first reaching the Caribbean and now extending to Central, South and North America. It is therefore considered a major public health and economic threat. CHIKV causes febrile illness typically associated with debilitating joint pains. In rare cases, it may also cause central nervous system disease, notably in neonates. Joint symptoms may persist for months to years, and lead to arthritis. This review focuses on the spectrum of signs and symptoms associated with CHIKV infection in humans. It also illustrates how the analysis of clinical and biological data from human cohorts and the development of animal and cellular models of infection has helped to identify the tissue and cell tropisms of the virus and to decipher host responses in benign, severe or persistent disease. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World".

Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review

“…The acute stage extends from the first symptomatic day to the 21 st day and is characterized by an end-of-incubation sudden high fever (often above 39ºC), headaches, myalgia and the insidious onset of typical symmetric, bilateral polyarthalgia (most frequently of small distal joints – phalanges, wrists, ankles), along with a typical maculopapular evanescent rash 1, 3, 9 . The location of the arthralgias tends to vary between individuals.…”

“…The word “Chikungunya” means “which contorts or bends up” in Makonde language from Tanzania and Mozambique, referring accurately to the difficulty in deambulation or walking of those affected 1, 2 . Despite CHIKV first being documented in 1954 in Tanzania, Africa and subsequently Asia 1, 3, 4 , it was not until 2006 that CHIKV first alarmed the world for being a major public health concern. After an explosive epidemic outbreak in French island La Réunion, where 35% of the total population was infected over six months, CHIKV arrived to central France and extended to Germany, Italy, Norway, and Switzerland 1 .…”

“…After an explosive epidemic outbreak in French island La Réunion, where 35% of the total population was infected over six months, CHIKV arrived to central France and extended to Germany, Italy, Norway, and Switzerland 1 . Later on, the virus hit North, Central and South America and brought with it the concept of a “self-limited febrile illness”, a more benign type of infection with predominantly articular symptomatology 1, 3– 5 .…”

“…“Old World” viruses such as CHIKV are known for their articular tropism and exanthematous febrile syndrome; and the “New World” viruses such as the western equine encephalitis and Venezuelan equine encephalitis viruses 1– 3 have preference for nervous system stromal cells. CHIKV infection pathway in humans is shared with Dengue fever, and is caused by the biting of borne-arthropods from the Aedes mosquito family, Aedes aegypti and most recently Aedes albopictus 1 , the last one being essential to the wide geographic colonization process ever since a new mutation (A226V) in CHIKV has conferred the virus a better ability to replicate in this species.…”

“…Not every patient develops the full three stages, and at least a 20% of the infected population will not develop any symptoms at all, despite serological confirmation 3, 9 . On the other hand, isolated cases have reported severe acute manifestations, far from the classic expected evolution of the disease, especially in areas with renowned late outbreaks such as India (2006) 1, 10 , La Réunion and Mayotte (France, 2006) 9, 11 , Malaysia (2008), Thailand (2008) 12, 13 and South America (Colombia, Venezuela and later Brazil, from 2014 until now) 14, 15 .…”