Implementation and Evaluation of Guillain-Barré Syndrome Surveillance in Puerto Rico during the 2016 Zika Virus Epidemic.

OBJECTIVE: Guillain-Barré syndrome (GBS) is an uncommon autoimmune disorder that follows infection or vaccination, and increased incidence has been reported during Zika virus (ZIKV) transmission. During the 2016 ZIKV epidemic, the Puerto Rico Department of Health (PRDH) implemented the Enhanced GBS Surveillance System (EGBSSS). Here, we describe EGBSSS implementation and evaluate completeness, validity, and timeliness. METHODS: GBS cases were identified using passive surveillance and discharge diagnostic code for GBS. Completeness was evaluated by capture-recapture methods. Sensitivity and positive predictive value (PPV) for confirmed GBS cases were calculated for both case identification methods. Median time to completion of key time steps were compared by quarter (Q1-4) and hospital size. RESULTS: A total of 122 confirmed GBS cases with onset of neurologic illness in 2016 were identified. Capture-recapture methodology estimated that four confirmed GBS cases were missed by both identification methods. Identification of cases by diagnostic code had a higher sensitivity than passive surveillance (89% vs. 80%), but a lower PPV (60% vs. 72%). There was a significant decrease from Q1 to Q3 in median time from hospital admission to case reporting (11 days vs. 2 days, p = 0.032) and from Q2 to Q3 in median time from specimen receipt to arbovirus laboratory test reporting (35 days vs. 26 days, p = 0.004). CONCLUSION: EGBSSS provided complete, valid, and increasingly timely surveillance data, which guided public health action and supported healthcare providers during the ZIKV epidemic. This evaluation provides programmatic lessons for GBS surveillance and emergency response surveillance.

Clinical Features of Guillain-Barré Syndrome With vs Without Zika Virus Infection, Puerto Rico, 2016.

Importance: The pathophysiologic mechanisms of Guillain-Barré syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. Objective: To identify specific clinical features of GBS associated with ZIKV infection. Design, Setting, and Participants: During the ZIKV epidemic in Puerto Rico, prospective and retrospective strategies were used to identify patients with GBS who had neurologic illness onset in 2016 and were hospitalized at all 57 nonspecialized hospitals and 2 rehabilitation centers in Puerto Rico. Guillain-Barré syndrome diagnosis was confirmed via medical record review using the Brighton Collaboration criteria. Specimens (serum, urine, cerebrospinal fluid, and saliva) from patients with GBS were tested for evidence of ZIKV infection by real-time reverse transcriptase-polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. In this analysis of public health surveillance data, a total of 123 confirmed GBS cases were identified, of which 107 had specimens submitted for testing; there were 71 patients with and 36 patients without evidence of ZIKV infection. Follow-up telephone interviews with patients were conducted 6 months after neurologic illness onset; 60 patients with and 27 patients without evidence of ZIKV infection participated. Main Outcomes and Measures: Acute and long-term clinical characteristics of GBS associated with ZIKV infection. Results: Of 123 patients with confirmed GBS, the median age was 54 years (age range, 4-88 years), and 68 patients (55.3%) were male. The following clinical features were more frequent among patients with GBS and evidence of ZIKV infection compared with patients with GBS without evidence of ZIKV infection: facial weakness (44 [62.0%] vs 10 [27.8%]; P < .001), dysphagia (38 [53.5%] vs 9 [25.0%]; P = .005), shortness of breath (33 [46.5%] vs 9 [25.0%]; P = .03), facial paresthesia (13 [18.3%] vs 1 [2.8%]; P = .03), elevated levels of protein in cerebrospinal fluid (49 [94.2%] vs 23 [71.9%]; P = .008), admission to the intensive care unit (47 [66.2%] vs 16 [44.4%]; P = .03), and required mechanical ventilation (22 [31.0%] vs 4 [11.1%]; P = .02). Six months after neurologic illness onset, patients with GBS and evidence of ZIKV infection more frequently reported having excessive or inadequate tearing (30 [53.6%] vs 6 [26.1%]; P = .03), difficulty drinking from a cup (10 [17.9%] vs 0; P = .03), and self-reported substantial pain (15 [27.3%] vs 1 [4.3%]; P = .03). Conclusions and Relevance: In this study, GBS associated with ZIKV infection was found to have higher morbidity during the acute phase and more frequent cranial neuropathy during acute neuropathy and 6 months afterward. Results indicate GBS pathophysiologic mechanisms that may be more common after ZIKV infection.

Postmortem Findings in Patient with Guillain-Barré Syndrome and Zika Virus Infection.

Postmortem examination results of a patient with Guillain-Barré syndrome and confirmed Zika virus infection revealed demyelination of the sciatic and cranial IV nerves, providing evidence of the acute demyelinating inflammatory polyneuropathy Guillain-Barré syndrome variant. Lack of evidence of Zika virus in nervous tissue suggests that pathophysiology was antibody mediated without neurotropism.

Effects of cold ischemia time on hepatic allograft function / Efeitos do tempo de isquemia fria sobre os enxertos hepáticos

ABSTRACT Background : Cold ischemia time is related to success of liver transplantation. Aim : To compare the impact of cold ischemia time on allografts locally collected to those collected distantly. Methods : Were evaluated 83 transplantations. The patients were divided in two groups: those who received liver grafts collected from cities out of Curitiba (n=42) and locally (n=41). From the donors were compared: cause of death, days at ICU, cardiac arrest, vasoactive drugs, lab exams, gender, age, and BMI. Were compared the subsequent information of receptors: cold ischemia time, warm ischemia time, length of surgery, lab exams, etiology of cirrhosis, MELD score, age, gender, histology of graft, use of vasoactive drugs, and blood components transfusion. Were evaluated the correlation between cold ischemia time and lab results. Results : The liver grafts collected from other cities were submitted to a longer cold ischemia time (500±145 min) compared to those locally collected (317,85±105 min). Donors from other cities showed a higher serum sodium level at donation (154±16 mEq/dl) compared to those from Curitiba (144±10 mEq/dl). The length of cold ischemia time was related to serum levels of ALT and total bilirubin. Conclusion : Liver grafts distantly collected underwent longer cold ischemia times, although it caused neither histologic injuries nor higher transfusion demands. There is a correlation between cold ischemia time and hepatic injury, translated by elevation of serum ALT and total bilirubin levels.

RESUMO Racional : O tempo de isquemia fria está relacionado ao sucesso do transplante hepático. Objetivo : Comparar o impacto do tempo dela sobre enxertos captados localmente com os distantes. Métodos : Avaliaram-se 83 transplantes. Os pacientes foram divididos em dois grupos: enxertos captados fora de Curitiba (n=42) e captados localmente (n=41). Dos doadores compararam-se causa do óbito, dias de UTI, parada cardíaca, drogas vasoativas, exames laboratoriais, gênero, idade e IMC. Dos receptores seguintes dados: tempos de isquemia fria e morna, tempo operatório, exames laboratoriais, causa da cirrose, MELD, idade na operação, gênero, biópsia do enxerto, uso de drogas vasoativas e necessidade de transfusões. Foi realizada avaliação de correlação entre o tempo de isquemia fria e os exames laboratoriais. Resultados : Os enxertos captados à distância foram submetidos a maior tempo de isquemia fria (500,3±145 min) quando comparados aos captados localmente (317,85±105 min). Os doadores de fora apresentaram níveis mais elevados de sódio no momento da doação (154±16 mEq/dl) comparados aos doadores de Curitiba (144±10 mEq/dl). Houve correlação entre o tempo de isquemia fria e os níveis de ALT e de bilirrubina total. Não houve diferenças ao comparar-se os demais dados. Conclusão : Enxertos captados à distância sofreram maior tempo de isquemia fria. Isso não refletiu nos prejuízos histológicos nem na demanda transfusional durante o pós-operatório. Houve correlação entre o tempo de isquemia fria e o grau de lesão hepática avaliada pela ALT e pela bilirrubina total.

EFFECTS OF COLD ISCHEMIA TIME ON HEPATIC ALLOGRAFT FUNCTION.

BACKGROUND: Cold ischemia time is related to success of liver transplantation. AIM: To compare the impact of cold ischemia time on allografts locally collected to those collected distantly. METHODS: Were evaluated 83 transplantations. The patients were divided in two groups: those who received liver grafts collected from cities out of Curitiba (n=42) and locally (n=41). From the donors were compared: cause of death, days at ICU, cardiac arrest, vasoactive drugs, lab exams, gender, age, and BMI. Were compared the subsequent information of receptors: cold ischemia time, warm ischemia time, length of surgery, lab exams, etiology of cirrhosis, MELD score, age, gender, histology of graft, use of vasoactive drugs, and blood components transfusion. Were evaluated the correlation between cold ischemia time and lab results. RESULTS: The liver grafts collected from other cities were submitted to a longer cold ischemia time (500±145 min) compared to those locally collected (317,85±105 min). Donors from other cities showed a higher serum sodium level at donation (154±16 mEq/dl) compared to those from Curitiba (144±10 mEq/dl). The length of cold ischemia time was related to serum levels of ALT and total bilirubin. CONCLUSION: Liver grafts distantly collected underwent longer cold ischemia times, although it caused neither histologic injuries nor higher transfusion demands. There is a correlation between cold ischemia time and hepatic injury, translated by elevation of serum ALT and total bilirubin levels.

Guillain-Barré Syndrome During Ongoing Zika Virus Transmission - Puerto Rico, January 1-July 31, 2016.

Guillain-Barré syndrome (GBS) is a postinfectious autoimmune disorder characterized by bilateral flaccid limb weakness attributable to peripheral nerve damage (1). Increased GBS incidence has been reported in countries with local transmission of Zika virus, a flavivirus transmitted primarily by certain Aedes species mosquitoes (2). In Puerto Rico, three arthropod-borne viruses (arboviruses) are currently circulating: Zika, dengue, and chikungunya. The first locally acquired Zika virus infection in Puerto Rico was reported in December 2015 (3). In February 2016, the Puerto Rico Department of Health (PRDH), with assistance from CDC, implemented the GBS Passive Surveillance System (GBPSS) to identify new cases of suspected GBS (4). Fifty-six suspected cases of GBS with onset of neurologic signs during January 1-July 31, 2016, were identified. Thirty-four (61%) patients had evidence of Zika virus or flavivirus infection; the median age of these patients was 55 years (range = 21-88 years), and 20 (59%) patients were female. These 34 patients were residents of seven of eight PRDH public health regions. All 34 patients were hospitalized and treated with intravenous immunoglobulin G (IVIg), the standard treatment for GBS; 21 (62%) required intensive care unit admission, including 12 (35%) who required endotracheal intubation and mechanical ventilation. One patient died of septic shock after treatment for GBS. Additionally, 26 cases of neurologic conditions other than GBS were reported through GBPSS, including seven (27%) in patients with evidence of Zika virus or flavivirus infection. Residents of and travelers to Puerto Rico and countries with active Zika virus transmission should follow recommendations for prevention of Zika virus infections.* Persons with signs or symptoms consistent with GBS should promptly seek medical attention. Health care providers in areas with ongoing local transmission seeing patients with neurologic illnesses should consider GBS and report suspected cases to public health authorities.

Effect of a Dengue Clinical Case Management Course on Physician Practices in Puerto Rico.

BACKGROUND: Prior to 2010, the clinical management of dengue in Puerto Rico was inconsistent with World Health Organization guidelines. A 4-hour classroom-style course on dengue clinical management was developed in 2009 and mandated for Puerto Rico medical licensure in 2010. Fifty physicians were trained as "master trainers" and gave this course to 7638 physicians. This study evaluated the effect of the course on the clinical management of hospitalized dengue patients. METHODS: Pre- and post-course test responses were compared. Changes in physician practices were assessed by reviewing medical records of 430 adult and 1075 pediatric dengue patients at the 12 hospitals in Puerto Rico that reported the most cases during 2008-2009 (pre-intervention) and 2011 (post-intervention). Mixed-effects logistic regression was used to compare key indicators of dengue management. RESULTS: Physician test scores increased from 48% to 72% correct. Chart reviews showed that the percentage of adult patients who did not receive corticosteroids increased from 30% to 68% (odds ratio [OR], 5.9; 95% confidence interval [CI], 3.7-9.5) and from 91% to 96% in pediatric patients (OR, 2.7; 95% CI, 1.5-4.9). Usage of isotonic intravenous saline during the critical period increased from 57% to 90% in adult patients (OR, 6.2; 95% CI, 1.9-20.4) and from 25% to 44% in pediatric patients (OR, 3.4; 95% CI, 2.2-5.3). CONCLUSIONS: Management of dengue inpatients significantly improved following implementation of a classroom-style course taught by master trainers. An online version of the course was launched in 2014 to expand its reach and sustainability.

Probable and possible transfusion-transmitted dengue associated with NS1 antigen-negative but RNA confirmed-positive red blood cells.

BACKGROUND: In the absence of active blood donation screening, dengue viruses (DENV) have been implicated in only a limited number of transfusion transmissions worldwide. This study attempted to identify if blood from donors testing negative by an NS1-antigen (Ag) enzyme-linked immunosorbent assay (ELISA) but confirmed positive for DENV RNA caused DENV-related disease in recipients during the epidemic years of 2010 to 2012 in Puerto Rico. STUDY DESIGN AND METHODS: Donation aliquots testing negative by an investigational NS1-Ag ELISA were stored frozen and retested retrospectively using a research transcription-mediated amplification assay (TMA) detecting DENV RNA. All RNA-reactive donations were subject to confirmatory RNA and antibody testing. Recipient tracing was conducted for all components manufactured from TMA-reactive components. Medical chart review, recipient interview, and follow-up sampling occurred for 42 recipients transfused with TMA-reactive components. RESULTS: Six of 42 recipients developed new-onset fever in the 2 weeks posttransfusion; three (50%) received RNA confirmed-positive, NS1-Ag-negative red blood cell (RBC) units. One recipient of a high-titer unit (7 × 10(7) DENV-4 RNA copies/mL) developed severe dengue, and a second recipient had only fever recorded but had a negative sepsis work-up. New fever attributable to DENV infection in a third recipient was confounded by fever potentially attributable to posttransfusion sepsis. CONCLUSIONS: In our retrospective study, NS1-Ag detected 20% of all RNA confirmed-positive donations demonstrating limitations of NS1-Ag ELISA for blood donation screening. We identified one recipient with a clinical syndrome compatible with severe dengue who had received an NS1-Ag-negative but RNA confirmed-positive RBC unit. This investigation illustrates the difficulty in confirming transfusion transmission in dengue-endemic areas among severely ill transfusion recipients.