Resumen
La fiebre chikungunya es una enfermedad producida por un alfavirus perteneciente a la familia Togaviridae, transmitida por miembros de diferentes especies del género Aedes: Aedes aegypti y Aedes albopictus (A. albopictus). Es endémica en África y Asia, ocasionando brotes epidémicos recurrentes. En 2007, surge de forma emergente en Europa transmitida por A. albopictus, asentado en el área mediterránea. Los primeros casos autóctonos detectados recientemente en las islas caribeñas suponen una seria amenaza de propagación al continente americano, libre hasta el momento de la enfermedad.
Se manifiesta de forma aguda con fiebre, rash cutáneo y poliartritis. La mortalidad es baja, pero un porcentaje elevado de enfermos desarrollan una fase crónica definida por poliartritis persistente durante meses e incluso años.
Una severa reacción inmunitaria de defensa con incremento de citocinas proinflamatorias es la responsable de la inflamación articular. El tratamiento es sintomático. No disponemos de terapia antiviral específica ni vacuna preventiva. Por ello, debemos profundizar en el estudio de la inmunopatogénesis, con el fin encontrar dianas terapéuticas más apropiadas.
Keywords
Chikungunya fever; Chronic polyarthritis; Emergent outbreak; International alert
Palabras clave
Fiebre chikungunya; Poliartritis crónica; Epidemia emergente; Alerta internacional
Introduction
Chikungunya fever is a viral infection caused by a single-stranded RNA alphavirus belonging to the Togaviridae family. It is transmitted to humans by Aedes mosquitoes: Aedes aegypti (A. aegypti) and Aedes albopictus (A. albopictus). It is endemic in Africa and Asia, causing recurrent outbreaks. The spread of the disease through imported cases has caused outbreaks in indigenous regions of the Indian Ocean and Europe, as happened in northern Italy in 2007. 1
The notification, in December 2013, of the first indigenous cases in the territories of the Caribbean islands has alerted international authorities on the possibility of spread of the disease to the Americas, a continent so far free from the disease. Since then, the number of reported cases has progressively increased. The spread of the disease in a globalized world is causing alarm among global epidemiological health authorities. Multiple European travelers come each year to the region of the Caribbean islands, the current focus of the disease and may act as a vehicle to spread the disease to the European continent. Suitable climatic conditions for the development of the A. albopictus mosquito occur in the Mediterranean region of Europe favoring the colonization of this vector. Their presence has been detected in various regions of Spain. Therefore, Chikungunya fever could become, from imported cases, an emerging disease in our territory.
Clinically, the disease manifests itself as acute and abrupt fever, rash, joint pain/arthritis and fatigue that causes significant functional disability. The response to symptomatic treatment is slow, showing a high incidence of recurrence and chronicity at the joint level.2
A severe immune response to the viral infection is responsible for rheumatic manifestations. Current therapeutic resources are scarce. We have no effective antiviral treatment or vaccine, and response to symptomatic treatment is moderate. The study of the immunopathogenesis will lead us to more appropriate therapeutic targets.
Epidemiology and Natural History
Chikungunya virus (CHIKV) is a single-stranded RNA alphavirus belonging the Togaviridae family. Alphaviruses are small, spherical and encapsulated viruses, measuring 60–70 nm in diameter. Their replicative cycle is very fast, about 4 h. 2
The reservoir of CHIKV in its urban endemic/epidemic cycle is infected human beings, and transmission occurs primarily through the bite of mosquitoes of the Aedes genus: A. aegypti and A. albopictus. A. aegypti is widely distributed in the urban areas of the tropics and subtropics and is responsible for human transmission in endemic areas. A. albopictus, known in Spain as “Asian tiger mosquito”, is a more aggressive mosquito, active throughout the day and with longer lifetime. The use of plastic containers and climate change in developing countries have facilitated the spread of this vector, expanding to other geographical areas through transport containers and tires from Asia. 3Environmental changes have also led to a suitable habitat for vector development in recipient countries. 4Moreover, in the course of the epidemic in the Indian Ocean, there was a mutation in the E1 protein (A226V) of CHIKV, conferring an evolutionary advantage in replication to the A. albopictus mosquito, the main vector involved in the epidemic. 5 In Spain, the A. albopictus vector is present at least since 2004, when it was first detected in Sant Cugat del Vallès (Barcelona). In late 2012, the vector had established in many cities of the Mediterranean coast (Girona to Murcia, with the exception of Valencia) and Mallorca, making it impossible to rule out its circulation to areas of the Ebro Valley. 6
CHIKV was first isolated in Tanzania in 1952. Initially, it remained limited to East Africa and Southeast Asia, causing massive epidemics, such as the one that occurred between 1999 and 2000 in the Democratic Republic of Congo, which affected some 50 000 people, and the one that in 2000–2003 occurred in Indonesia. In 2004 it began a process of global expansion, characterized by various epidemics affecting 5–10 million people.7 In 2004 propagation was produced, from Kenya, of a new virus variant (A226V) adapted to the A. albopictus vector, to the islands of the Indian Ocean. 5 The epidemic in Réunion island (2006–2007) attracted worldwide interest in this disease as a result of the significant economic and social impact produced in a zone with an elevated sociosanitary development. 8 From the beginning of the epidemic, more than 1000 cases of imported CHIKV have been detected in European and American travelers arriving from affected areas. 4 Between July and September 2007, 205 indigenous cases of Chikungunya fever were detected in Italy, 175 confirmed, constituting the first autoctonous epidemic in Europe. The cases disappeared after a drop in temperature, and no new cases have been recorded so far. 9 In 2010, 2 new cases of local transmission occurred on the southwestern coast of France. 10 As for Spain, since 2006, several imported cases have been notified. Seco Sanchez et al. analyzed 11 the presence of the infection in 308 travelers with clinical manifestations of the disease who came from endemic areas.PCR and culture were used for detection. 29 cases were diagnosed in total, 9 in travelers from the western islands of the Indian Ocean and 20 in India. These cases occurred between 2006 and 2007, coinciding with epidemic outbreaks in these geographical areas. Confirmation of Chikungunya fever imported into Spain has promoted the adoption, in 2013, of a monitoring protocol designed to avoid the occurrence of cases and preventing vector settlement. 12
Today, a new outbreak is emerging in the region of the Caribbean islands. In December 2013, the publication of the first indigenous cases of Chikungunya reported in America, covering the territories of the Caribbean islands: British Virgin Islands, Guadeloupe, Martinique, St. Barthelemy, St. Maarten (Dutch) St. Martin (French), French Guiana, Dominica, Anguilla and Aruba, Santo Domingo and Haiti, with 130,941 suspected cases and 4486 confirmed cases (June 6, 2014, last updated by WHO).13 The disease spreads quickly and progressively. The emergence of Chikungunya fever as an emerging disease in the Americas has led to the publication by the WHO (24 January 2014) of a series of recommendations to prevent the progression of indigenous transmission of this disease.14 and 15
Clinical Manifestations
The bite of an infected mosquito in humans produces manifestations of the disease in 95% of cases. After CHIKV infection, a silent incubation period occurs lasting 2–4 days. After this short period, the acute period of the disease occurs abruptly, coinciding with maximum viremia. It occurs with high fever, followed within hours by myalgia, joint pain and generalized, severe and disabling arthritis, accompanied by headache, backache and1 maculopapular rash, predominantly on the thorax. Sometimes, facial edema and bullous dermatitis can also appear, specially in children.16 and 17 The acute phase reactants are normal or moderately elevated. There may be leucopenia, lymphopenia and thrombocytopenia. Among the ophthalmologic manifestations described, we found anterior uveitis, retinal vasculitis with a subsequently benign course, with resolution in 6–8 weeks.18 and 19 Less common manifestations are myopericarditis, massive toxic hepatitis and meningoencephalitis. After this acute episode of 7–10 days, a high percentage of patients start the chronic phase of the disease. This is manifested in the form of persistent polyarthritis/polyarthralgia, accompanied by morning stiffness and fatigue, which remains even after 3 years.20
Fetal-maternal transmission of the virus is possible. Out of 35 pregnant women with confirmed disease at the time of delivery, 30 transmitted the disease to infants, constituting the first cases of fetomaternal transmission documented.21 Subsequently, other cases have been published by various authors. Likewise, transmission may occur through blood transfusion. This caused considerable problems for the Italian health authorities during the epidemic that affected its territory in 2007; the application of the precautionary measures taken by the blood banks led to a considerable drop in blood products.22
Chikungunya fever cannot be considered a serious disease in terms of mortality refers.23 Its incidence is low and, for the most part, occurs in patients over 65. Its severity lies in the massive involvement of numerous individuals, as well as the chronicity