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.

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.

Comparative analysis of the myoglobin gene in whales and humans reveals evolutionary changes in regulatory elements and expression levels.

Cetacea and other diving mammals have undergone numerous adaptations to their aquatic environment, among them high levels of the oxygen-carrying intracellular hemoprotein myoglobin in skeletal muscles. Hypotheses regarding the mechanisms leading to these high myoglobin levels often invoke the induction of gene expression by exercise, hypoxia, and other physiological gene regulatory pathways. Here we explore an alternative hypothesis: that cetacean myoglobin genes have evolved high levels of transcription driven by the intrinsic developmental mechanisms that drive muscle cell differentiation. We have used luciferase assays in differentiated C2C12 cells to test this hypothesis. Contrary to our hypothesis, we find that the myoglobin gene from the minke whale, Balaenoptera acutorostrata, shows a low level of expression, only about 8% that of humans. This low expression level is broadly shared among cetaceans and artiodactylans. Previous work on regulation of the human gene has identified a core muscle-specific enhancer comprised of two regions, the "AT element" and a C-rich sequence 5' of the AT element termed the "CCAC-box". Analysis of the minke whale gene supports the importance of the AT element, but the minke whale CCAC-box ortholog has little effect. Instead, critical positive input has been identified in a G-rich region 3' of the AT element. Also, a conserved E-box in exon 1 positively affects expression, despite having been assigned a repressive role in the human gene. Last, a novel region 5' of the core enhancer has been identified, which we hypothesize may function as a boundary element. These results illustrate regulatory flexibility during evolution. We discuss the possibility that low transcription levels are actually beneficial, and that evolution of the myoglobin protein toward enhanced stability is a critical factor in the accumulation of high myoglobin levels in adult cetacean muscle tissue.

Development and Content Validity of a Disability Self-Management Questionnaire for Hispanic Older Adults.

OBJECTIVE: There is no Spanish-language instrument for assessing the self-management strategies used by older adults with physical function disabilities to manage the difficulties that can occur in daily living activities. This study aimed to design and test the content validity of a Spanish version of the newly developed Self-Management of Function in Daily Living Activities Questionnaire (SF-DLAQ). METHODS: A methodological study, guided by the Person-Environment-Occupation-Performance (PEOP) model, was conducted to develop the SF-DLAQ. Stage 1 focused on designing the questionnaire, doing so using qualitative data obtained from 24 older adults and obtained from 10 existing scales that measure the self-management of chronic conditions. Stage 2 focused on expert judgement, which consisted of validating the questionnaire with 8 experts in aging using an item-level content validity index (I-CVI), a scale-level CVI (S-CVI), and the kappa statistic. RESULTS: All the scores that were attained in stage 2 were favorable, with those of the I-CVI for clarity ranging from 0.09 to 1.0 and those of the I-CVI for relevancy, the S-CVI, and the kappa all being 1.0. CONCLUSION: The scale and item validity for the SF-DLAQ, Spanish version, has been demonstrated but should be confirmed with further testing.

Indium Tin-Doped Oxide (ITO) as a High Activity Water Oxidation Photoanode.

Photochemical water oxidation was carried out at a mesoporous nanoparticle film composed of indium tin-doped oxide (nanoITO). Annealing nanoITO at temperatures above 250 °C affects both conducting and semiconducting properties. Impressive photoelectrochemical activity was observed at this degenerate n-type semiconductor electrode, outperforming the traditional semiconductor titanium dioxide (TiO2) under the same conditions. In a 0.1 M HNO3 solution, the nanoITO electrode sustained photocurrents of 1.0 mA/cm2 at an Eapplied = 1.5 V vs saturated calomel electrode (SCE) (η = 0.55 V) under a 90 mW/cm2 UV illumination (375 nm). This activity is compared to ∼0.3 mA/cm2 with a traditional TiO2 electrode under the same potential and conditions. Evidence for oxygen generation in the photolysis experiments was quantified using the collector-generator method, and >70% photocurrent efficiency for O2 production was confirmed at this nanoITO photoanode.

Assessment of community support for Wolbachia-mediated population suppression as a control method for Aedes aegypti mosquitoes in a community cohort in Puerto Rico.

Arboviral diseases transmitted by Aedes species mosquitoes pose an increasing public health challenge in tropical regions. Wolbachia-mediated population suppression (Wolbachia suppression) is a vector control method used to reduce Aedes mosquito populations by introducing male mosquitoes infected with Wolbachia, a naturally occurring endosymbiotic bacterium. When Wolbachia-infected male mosquitoes mate with female wild mosquitoes, the resulting eggs will not hatch. Public support is vital to the successful implementation and sustainability of vector control interventions. Communities Organized to Prevent Arboviruses (COPA) is a cohort study to determine the incidence of arboviral disease in Ponce, Puerto Rico and evaluate vector control methods. Focus groups were conducted with residents of COPA communities to gather their opinion on vector control methods; during 2018-2019, adult COPA participants were interviewed regarding their views on Wolbachia suppression; and a follow-up questionnaire was conducted among a subset of participants and non-participants residing in COPA communities. We analyzed factors associated with support for this method. Among 1,528 participants in the baseline survey, median age was 37 years and 63% were female. A total of 1,032 (68%) respondents supported Wolbachia suppression. Respondents with an income of $40,000 or more were 1.34 times as likely [95% CI: 1.03, 1.37] to support Wolbachia suppression than those who earned less than $40,000 annually. Respondents who reported repellant use were 1.19 times as likely to support Wolbachia suppression [95% CI: 1.03, 1.37]. A follow-up survey in 2020 showed that most COPA participants (86%) and non-participants living in COPA communities (84%) supported Wolbachia suppression during and after an educational campaign. The most frequent questions regarding this method were related to its impact on human and animal health, and the environment. Continuous community engagement and education efforts before and during the implementation of novel vector control interventions are necessary to increase and maintain community support.

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.