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 aims to determine the association between these arboviruses and GBS in a Mexican population and to establish the clinical characteristics of the patients, including the severity of the infection. A case-control study was conducted (2016/07/01-2018/06/30) in Instituto Mexicano del Seguro Social (Mexican Social Security Institute) hospitals, using serum and urine samples that were collected to determine exposure to ZIKV, DENV, CHIKV by RT-qPCR and serology (IgM). For the categorical variables analysis, Pearson’s χ2 or Fisher exact tests were used, and the Mann-Whitney U test for continuous variables. To determine the association of GBS and viral infection diagnosis through laboratory and symptomatology before admission, we calculated the odds ratio (OR) and 95% confidence intervals (95%CI) using a 2x2 contingency table. A p-value ≤ 0.05 was considered as significant. Ninety-seven GBS cases and 184 controls were included. The association of GBS with ZIKV acute infection (OR, 8.04; 95% CI, 0.89–73.01, p = 0.047), as well as laboratory evidence of ZIKV infection (OR, 16.45; 95% CI, 2.03–133.56; p = 0.001) or Flavivirus (ZIKV and DENV) infection (OR, 6.35; 95% CI, 1.99–20.28; p = 0.001) was observed. Cases of GBS associated with ZIKV demonstrated a greater impairment of functional status and a higher percentage of mechanical ventilation. According to laboratory results, an association between ZIKV or ZIKV and DENV infection in patients with GBS was found. Cases of GBS associated with ZIKV exhibited a more severe clinical picture. Cases with co-infection were not found.

43Background 44 Zika, dengue and chikungunya viruses (ZIKV, CHIKV and DENV) are temporally 45 associated with neurological diseases such as Guillain-Barré syndrome (GBS). 46 Because these three arboviruses coexist in Mexico, the frequency and severity of 47 GBS could theoretically increase. This study aimed to determine the association 48 between these arboviruses and GBS in a Mexican population, and to establish the 49 clinical features of the patients, including the severity of the infection. 50 Methodology/Principal findings 51 A case-control study was conducted (2016/07/01-2018/06/30) in hospitals from the 52 Instituto Mexicano del Seguro Social. Serum and urine samples were collected to 53 determine the exposure to ZIKV, DENV and CHIKV by RT-qPCR and serology 54 (IgM). The association between arboviral infection and GBS was analysed with χ 2 55 or exact Fisher tests and Kruskall-Wallis folloed by Mann Whitney U test for 56 comparing symptomatology. A p ≤ 0.05 was considered as significant. Ninety-57 seven GBS cases and 184 controls were included. Evidence of association of GBS 58 with ZIKV acute infection (OR, 8.04; 95% CI, 0.89-73.01, p =0.047), as well as 59 ZIKV recent infection (OR, 16.68; 95% CI, 2.05-135.31; p = 0.001) and Flavivirus 60 (ZIKV and DENV) recent infection (OR, 5.8; 95% CI, 1.8-18.8; p = 0.002) was 61 observed. Cases with GBS associated with ZIKV demonstrated a greater 62 impairment of functional status, a higher percentage of mechanical ventilation and 63 mortality. Dizziness, ataxia and low blood pressure showed statistically signifant 4 64 differences in cases with GBS associated with DENV. Co-infection cases were not 65 observed. 66 Conclusions/Significance 67 According to the laboratory results, an association between ZIKV or ZIKV and 68 DENV infection in patients with GBS was found. Cases of GBS associated with 69 ZIKV but not with DENV exhibited a more severe clinical picture. Cases with co-70 infection were not found.71 72 Author summary 73 Dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) are considered as 74 emerging or re-emerging viruses. In recent years, these viruses have produced 75 great epidemics in tropical climate urban centers, and have been associated with 76 neurological manifestations, including Guillain-Barre syndrome (GBS), which 77 causes muscle weakness, unstable gait, and decreased or absent musculoskeletal 78 reflexes. This study aimed to investigate the association between these viral 79 infections and GBS. A case and control study was conducted nationwide, including 80 97 cases of GBS and 184 controls matched by age, gender, and locality, but 81 without the disease. This study showed the positive association between GBS 82 cases and ZIKV or ZIKV and DENV infection. GBS cases associated with ZIKV 83 showed a more severe clinical picture (more impairment of functional status and 84 incapacity, a higher percentage of mechanical ventilation, and mortality). GBS 85 associated with DENV cases seemed to show more dizziness, ataxia, and low 86 blood pressure....

The Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) virus infections have been linked to Guillain-Barré syndrome (GBS). GBS has an estimated lethality of 4% to 8%, even with effective treatment. Mexico is considered a hyperendemic country for DENV due to the circulation of four serotypes, and the ZIKV and CHIKV viruses have also been circulating in the country. The objective of this study was to predict the number of GBS cases in relation to the cumulative incidence of ZIKV / DENV / CHIKV in Mexico from 2014 to 2019. A six-year time series ecological study was carried out from GBS cases registered in the Acute Flaccid Paralysis (AFP) Epidemiological Surveillance System (ESS), and DENV, ZIKV and CHIKV estimated cases from cases registered in the epidemiological vector-borne diseases surveillance system. The results shows that the incidence of GBS in Mexico is positively correlated with DENV and ZIKV. For every 1,000 estimated DENV cases, 1.45 GBS cases occurred on average, and for every 1,000 estimated ZIKV cases, 1.93 GBS cases occurred on average. A negative correlation between GBS and CHIKV estimated cases was found. The increase in the incidence of GBS cases in Mexico can be predicted by observing DENV and ZIKV cases through the epidemiological surveillance systems. These results can be useful in public health by providing the opportunity to improve capacities for the prevention of arbovirus diseases and for the timely procurement of supplies for the treatment of GBS.