Zika and dengue but not chikungunya are associated with Guillain-Barré syndrome in Mexico: a case-control study
Authors: Grijalva Israel , Grajales-Muñiz Concepción , González-Bonilla César , Borja-Aburto Victor Hugo , Paredes-Cruz Martín , Guerrero-Cantera José , González-Ibarra Joaquín , Vallejos-Parás Alfonso , Rojas-Mendoza Teresita , Santacruz-Tinoco Clara Esperanza , Hernández-Bautista Porfirio , Arriaga-Nieto Lumumba , Garza-Sagástegui María , Vargas-Ramos Ignacio , Sepúlveda-Núñez Ana , Campos-Villarreal Omar Israel , Corrales-Pérez Roberto , Azuara-Castillo Mallela , Sierra-González Elsa , Meza-Medina José Alfonso , Martínez-Miguel Bernardo , López-Becerril Gabriela , Ramos-Orozco Jessica , Muñoz-Guerrero Tomás , Gutiérrez-Lozano María Soledad , Cervantes-Ocampo Arlette Areli 
Published: January 2020

Background

Zika, dengue and chikungunya viruses (ZIKV, CHIKV and DENV) are temporally associated with neurological diseases such as Guillain-Barré syndrome (GBS). Because these three arboviruses coexist in Mexico, the frequency and severity of GBS could theoretically increase. This study aimed to determine the association between these arboviruses and GBS in a Mexican population, and to establish the clinical features of the patients, including the severity of the infection.

Methodology/Principal findings

A case-control study was conducted (2016/07/01-2018/06/30) in hospitals from the Instituto Mexicano del Seguro Social. Serum and urine samples were collected to determine the exposure to ZIKV, DENV and CHIKV by RT-qPCR and serology (IgM). The association between arboviral infection and GBS was analysed with χ2or exact Fisher tests and Kruskall-Wallis folloed by Mann Whitney U test for comparing symptomatology. A p ≤ 0.05 was considered as significant. Ninety-seven GBS cases and 184 controls were included. Evidence of association of GBS with ZIKV acute infection (OR, 8.04; 95% CI, 0.89–73.01, p =0.047), as well as ZIKV recent infection (OR, 16.68; 95% CI, 2.05–135.31; p = 0.001) and Flavivirus (ZIKV and DENV) recent infection (OR, 5.8; 95% CI, 1.8-18.8; p = 0.002) was observed. Cases with GBS associated with ZIKV demonstrated a greater impairment of functional status, a higher percentage of mechanical ventilation and mortality. Dizziness, ataxia and low blood pressure showed statistically signifant differences in cases with GBS associated with DENV. Co-infection cases were not observed.

Conclusions/Significance

According to the laboratory results, an association between ZIKV or ZIKV and DENV infection in patients with GBS was found. Cases of GBS associated with ZIKV but not with DENV exhibited a more severe clinical picture. Cases with co-infection were not found.

Author summary

Dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) are considered as emerging or re-emerging viruses. In recent years, these viruses have produced great epidemics in tropical climate urban centers, and have been associated with neurological manifestations, including Guillain-Barre syndrome (GBS), which causes muscle weakness, unstable gait, and decreased or absent musculoskeletal reflexes. This study aimed to investigate the association between these viral infections and GBS. A case and control study was conducted nationwide, including 97 cases of GBS and 184 controls matched by age, gender, and locality, but without the disease. This study showed the positive association between GBS cases and ZIKV or ZIKV and DENV infection. GBS cases associated with ZIKV showed a more severe clinical picture (more impairment of functional status and incapacity, a higher percentage of mechanical ventilation, and mortality). GBS associated with DENV cases seemed to show more dizziness, ataxia, and low blood pressure. Finally, the symptoms of ZIKV or DENV suspected disease before the development of GBS were similar to some previous reports. The impact of the interaction of these three arboviruses, particularly ZIKV, on the health of the Mexican population was less than expected. The Mexican experience could be useful for other populations.