Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders.
OBJECTIVE
The acute manifestations of dengue are well known. The clinical symptoms that present during the convalescent phase of infection are less well characterized, but may be autoimmune-based. This study was undertaken to determine the prevalence of persistent clinical symptoms among individuals infected during the 2006 Cuban epidemic and to evaluate the immunological and genetic factors associated with their occurrence.


METHODS
In 2008, clinical data and blood samples were collected from a random sample of adult individuals diagnosed during the 2006 epidemic with dengue fever (DF, n=68), dengue hemorrhagic fever (DHF, n=29), or an asymptomatic infection (AI, n=42). The presence of persistent symptoms was evaluated in all individuals and a psychological assessment was performed. IgG titers and the Fc receptor (FcR) were also evaluated. The following autoimmune markers were assessed in a subset (n=26) of symptomatic individuals: complement factors C3/C4, rheumatoid factor (RF), C-reactive protein (CRP), antinuclear antibodies (ANA), and immune complex (IC).


RESULTS
Over half (55/97) the individuals with a prior of diagnosis of DF or DHF had persistent clinical symptoms in the 2 years following infection. The sequelae were unrelated to the initial diagnosis and were more common among women (44/55). No symptoms were reported in the AI group and all study participants had normal mental and cognitive function. Persistent clinical symptoms were associated with HH polymorphic variant (p=0.027) and high IgG titer (p=0.041). Autoimmune marker alterations were common (20/26) in the subset of symptomatic individuals evaluated.


CONCLUSIONS
Clinical sequelae after recovery from an acute dengue virus infection are common in the 2 years following infection. The results obtained in this study suggest that persistent symptoms are associated with alterations in some immunological parameters and FcγRIIa gene polymorphism. This could suggest an autoimmune-based disturbance.
Tropical Medicine Institute Pedro Kourí, Autopista Novia del Mediodía, Km 6, entre Autopista Nacional y Carretera Central, La Lisa, Apartado 601, Marianao 13, C. Havana, Cuba. gmd@ipk.sld.cu
Gissel
G
García
Narjara
N
González
Ana Beatriz
AB
Pérez
Beatriz
B
Sierra
Eglis
E
Aguirre
Damaris
D
Rizo
Alienys
A
Izquierdo
Lizet
L
Sánchez
Danay
D
Díaz
Magnolia
M
Lezcay
Betsi
B
Pacheco
Kenji
K
Hirayama
Maria G
MG
Guzmán
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology / Q000821:virology*; D015415:Biomarkers / Q000097:blood; D003462:Cuba; D003715:Dengue / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D015415:Biomarkers; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG