Zika Virus infection and Guillain-Barré syndrome in Northeastern Mexico: A case-control study.

BACKGROUND: Beginning August 2017, we conducted a prospective case-control investigation in Monterrey, Mexico to assess the association between Zika virus (ZIKV) and Guillain-Barré syndrome (GBS). METHODS: For each of 50 GBS case-patients, we enrolled 2-3 afebrile controls (141 controls in total) matched by sex, age group, and presentation to same hospital within 7 days. RESULTS: PCR results for ZIKV in blood and/or urine were available on all subjects; serum ZIKV IgM antibody for 52% of case-patients and 80% of controls. Subjects were asked about antecedent illness in the two months prior to neurological onset (for case-patients) or interview (for controls). Laboratory evidence of ZIKV infection alone (PCR+ or IgM+) was not significantly different between case-patients and controls (OR: 1.26, 95% CI: 0.45-3.54) but antecedent symptomatic ZIKV infection [a typical ZIKV symptom (rash, joint pain, or conjunctivitis) plus laboratory evidence of ZIKV infection] was higher among case-patients (OR: 12.45, 95% CI: 1.45-106.64). GBS case-patients with laboratory evidence of ZIKV infection were significantly more likely to have had typical ZIKV symptoms than controls with laboratory evidence of ZIKV infection (OR: 17.5, 95% CI: 3.2-96.6). This association remained significant even when only GBS case-patients who were afebrile for 5 days before onset were included in the analysis, (OR 9.57 (95% CI: 1.07 to 85.35). CONCLUSIONS: During ZIKV epidemics, this study indicates that increases in GBS will occur primarily among those with antecedent symptomatic ZIKV.

Long-term outcomes of Guillain-Barré syndrome possibly associated with Zika virus infection.

BACKGROUND: This prospective cohort investigation analyzed the long-term functional and neurologic outcomes of patients with Zika virus-associated Guillain-Barré syndrome (GBS) in Barranquilla, Colombia. METHODS: Thirty-four Zika virus-associated GBS cases were assessed a median of 17 months following acute GBS illness. We assessed demographics, results of Overall Disability Sum Scores (ODSS), Hughes Disability Score (HDS), Zung Depression Scale (ZDS), and Health Related Quality of Life (HRQL) questionnaires; and compared outcomes indices with a normative sample of neighborhood-selected control subjects in Barranquilla without GBS. RESULTS: Median age at time of acute neurologic onset was 49 years (range, 10-80); 17 (50%) were male. No deaths occurred. At long-term follow-up, 25 (73%) patients had a HDS 0-1, indicating complete / near complete recovery. Among the group, HDS (mean 1.4, range 0-4), ODSS (mean 1.9, range 0-9) and ZDS score (mean 34.4, range 20-56) indicated mild / moderate ongoing disability. Adjusting for age and sex, Zika virus-associated GBS cases were similar to a population comparison group (n = 368) in Barranquilla without GBS in terms of prevalence of physical or mental health complaints, though GBS patients were more likely to have an ODSS of ≥ 1 (OR 8.8, 95% CI 3.2-24.5) and to suffer from moderate / moderate-severe depression (OR 3.89, 95% CI 1.23-11.17) than the comparison group. CONCLUSIONS: Long-term outcomes of Zika virus-associated GBS are consistent with those associated with other antecedent antigenic stimuli in terms of mortality and ongoing long-term morbidity, as published in the literature. Persons with Zika virus-associated GBS more frequently reported disability and depression after approximately one year compared with those without GBS.

Increased rates of Guillain-Barré syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil.

In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barré syndrome (GBS), coinciding with the introduction and spread of Zika virus (ZIKV). We found that GBS incidence during April-July 2015 among those ≥12 years of age was 5.6 cases/100,000 population/year and increased markedly with increasing age to 14.7 among those ≥60 years of age. We conducted interviews with 41 case-patients and 85 neighborhood controls and found no differences in demographics or exposures prior to GBS-symptom onset. A higher proportion of case-patients (83%) compared to controls (21%) reported an antecedent illness (OR 18.1, CI 6.9-47.5), most commonly characterized by rash, headache, fever, and myalgias, within a median of 8 days prior to GBS onset. Our investigation confirmed an outbreak of GBS, particularly in older adults, that was strongly associated with Zika-like illness and geo-temporally associated with ZIKV transmission, suggesting that ZIKV may result in severe neurologic complications.

Cardiac Complications, Earlier Treatment, and Initial Disease Severity in Kawasaki Disease.

OBJECTIVES: To assess if observed higher observed risks of cardiac complications for patients with Kawasaki disease (KD) treated earlier may reflect bias due to confounding from initial disease severity, as opposed to any negative effect of earlier treatment. STUDY DESIGN: We used data from Japanese nationwide KD surveys from 1997 to 2004. Receipt of additional intravenous immunoglobulin (IVIG) (data available all years) or any additional treatment (available for 2003-2004) were assessed as proxies for initial disease severity. We determined associations between earlier or later IVIG treatment (defined as receipt of IVIG on days 1-4 vs days 5-10 of illness) and cardiac complications by stratifying by receipt of additional treatment or by using logistic modeling to control for the effect of receiving additional treatment. RESULTS: A total of 48 310 patients with KD were included in the analysis. In unadjusted analysis, earlier IVIG treatment was associated with a higher risk for 4 categories of cardiac complications, including all major cardiac complications (risk ratio, 1.10; 95% CI, 1.06-1.15). Stratifying by receipt of additional treatment removed this association, and earlier IVIG treatment became protective against all major cardiac complications when controlling for any additional treatment in logistic regressions (OR, 0.90; 95% CI, 0.80-1.00). CONCLUSIONS: Observed higher risks of cardiac complications among patients with KD receiving IVIG treatment on days 1-4 of the illness are most likely due to underlying higher initial disease severity, and patients with KD should continue to be treated with IVIG as early as possible.

Clinical assessment of self-reported acute flaccid paralysis in a population-based setting in Guatemala.

Historically, poliovirus infection has been an important cause of acute flaccid paralysis (AFP) worldwide; however, successful elimination of wild-type poliovirus in much of the world has highlighted the importance of other causes of AFP. Despite the evolving etiology, AFP surveillance in most developing countries still focuses on poliovirus detection and fails to detect many AFP cases, particularly among adults. We assessed 41 subjects self-reporting symptoms suggestive of AFP during a population-based health survey in the Department of Santa Rosa, Guatemala. Thirty-five (85%) of the suspected cases were not hospitalized. Most subjects (37) did not have features consistent with AFP or had other diagnoses explaining weakness. We identified two adults who had not received medical attention for a clinical illness consistent with Guillain-Barré syndrome, the most important cause of non-poliovirus AFP. Usual surveillance methods for AFP, particularly in developing countries, may underestimate the true burden of non-poliovirus AFP.

Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients.

OBJECTIVE: Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions. STUDY DESIGN: A cohort (N=6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex. RESULTS: There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P<.0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P<.0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P<.0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P<.0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000. CONCLUSIONS: The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary-derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypoglycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism.