Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Borland E[original query] |
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Impact of SARS-CoV-2 infection on the association between laboratory tests and severe outcomes among hospitalized children
Xie J , Kuppermann N , Florin TA , Tancredi DJ , Funk AL , Kim K , Salvadori MI , Yock-Corrales A , Shah NP , Breslin KA , Chaudhari PP , Bergmann KR , Ahmad FA , Nebhrajani JR , Mintegi S , Gangoiti I , Plint AC , Avva UR , Gardiner MA , Malley R , Finkelstein Y , Dalziel SR , Bhatt M , Kannikeswaran N , Caperell K , Campos C , Sabhaney VJ , Chong SL , Lunoe MM , Rogers AJ , Becker SM , Borland ML , Sartori LF , Pavlicich V , Rino PB , Morrison AK , Neuman MI , Poonai N , Simon NE , Kam AJ , Kwok MY , Morris CR , Palumbo L , Ambroggio L , Navanandan N , Eckerle M , Klassen TP , Payne DC , Cherry JC , Waseem M , Dixon AC , Ferre IB , Freedman SB . Open Forum Infect Dis 2023 10 (10) ofad485 BACKGROUND: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. METHODS: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. RESULTS: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 10(9)/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 10(9)/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. CONCLUSIONS: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative. |
Exposure of Egyptian rousette bats (Rousettus aegyptiacus) and a little free-tailed bat (Chaerephon pumilus) to alphaviruses in Uganda
Kading RC , Borland EM , Mossel EC , Nakayiki T , Nalikka B , Ledermann JP , Crabtree MB , Panella NA , Nyakarahuka L , Gilbert AT , Kerbis-Peterhans JC , Towner JS , Amman BR , Sealy TK , Miller BR , Lutwama JJ , Kityo RM , Powers AM . Diseases 2022 10 (4) The reservoir for zoonotic o'nyong-nyong virus (ONNV) has remained unknown since this virus was first recognized in Uganda in 1959. Building on existing evidence for mosquito blood-feeding on various frugivorous bat species in Uganda, and seroprevalence for arboviruses among bats in Uganda, we sought to assess if serum samples collected from bats in Uganda demonstrated evidence of exposure to ONNV or the closely related zoonotic chikungunya virus (CHIKV). In total, 652 serum samples collected from six bat species were tested by plaque reduction neutralization test (PRNT) for neutralizing antibodies against ONNV and CHIKV. Forty out of 303 (13.2%) Egyptian rousettes from Maramagambo Forest and 1/13 (8%) little free-tailed bats from Banga Nakiwogo, Entebbe contained neutralizing antibodies against ONNV. In addition, 2/303 (0.7%) of these Egyptian rousettes contained neutralizing antibodies to CHIKV, and 8/303 (2.6%) contained neutralizing antibodies that were nonspecifically reactive to alphaviruses. These data support the interepidemic circulation of ONNV and CHIKV in Uganda, although Egyptian rousette bats are unlikely to serve as reservoirs for these viruses given the inconsistent occurrence of antibody-positive bats. |
Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.
Funk AL , Kuppermann N , Florin TA , Tancredi DJ , Xie J , Kim K , Finkelstein Y , Neuman MI , Salvadori MI , Yock-Corrales A , Breslin KA , Ambroggio L , Chaudhari PP , Bergmann KR , Gardiner MA , Nebhrajani JR , Campos C , Ahmad FA , Sartori LF , Navanandan N , Kannikeswaran N , Caperell K , Morris CR , Mintegi S , Gangoiti I , Sabhaney VJ , Plint AC , Klassen TP , Avva UR , Shah NP , Dixon AC , Lunoe MM , Becker SM , Rogers AJ , Pavlicich V , Dalziel SR , Payne DC , Malley R , Borland ML , Morrison AK , Bhatt M , Rino PB , Beneyto Ferre I , Eckerle M , Kam AJ , Chong SL , Palumbo L , Kwok MY , Cherry JC , Poonai N , Wassem M , Simon NJ , Freedman SB . JAMA Netw Open 2022 5 (7) e2223253 IMPORTANCE: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE: SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). CONCLUSIONS AND RELEVANCE: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older. |
Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.
Funk AL , Florin TA , Kuppermann N , Tancredi DJ , Xie J , Kim K , Neuman MI , Ambroggio L , Plint AC , Mintegi S , Klassen TP , Salvadori MI , Malley R , Payne DC , Simon NJ , Yock-Corrales A , Nebhrajani JR , Chaudhari PP , Breslin KA , Finkelstein Y , Campos C , Bergmann KR , Bhatt M , Ahmad FA , Gardiner MA , Avva UR , Shah NP , Sartori LF , Sabhaney VJ , Caperell K , Navanandan N , Borland ML , Morris CR , Gangoiti I , Pavlicich V , Kannikeswaran N , Lunoe MM , Rino PB , Kam AJ , Cherry JC , Rogers AJ , Chong SL , Palumbo L , Angelats CM , Morrison AK , Kwok MY , Becker SM , Dixon AC , Poonai N , Eckerle M , Wassem M , Dalziel SR , Freedman SB . JAMA Netw Open 2022 5 (1) e2142322 IMPORTANCE: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. OBJECTIVE: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. EXPOSURES: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. MAIN OUTCOMES AND MEASURES: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. RESULTS: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). CONCLUSIONS AND RELEVANCE: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions. |
Genomic characterization of 99 viruses from the bunyavirus families Nairoviridae, Peribunyaviridae, and Phenuiviridae, including 35 previously unsequenced viruses.
Kapuscinski ML , Bergren NA , Russell BJ , Lee JS , Borland EM , Hartman DA , King DC , Hughes HR , Burkhalter KL , Kading RC , Stenglein MD . PLoS Pathog 2021 17 (3) e1009315 Bunyaviruses (Negarnaviricota: Bunyavirales) are a large and diverse group of viruses that include important human, veterinary, and plant pathogens. The rapid characterization of known and new emerging pathogens depends on the availability of comprehensive reference sequence databases that can be used to match unknowns, infer evolutionary and pathogenic potential, and make response decisions in an evidence-based manner. In this study, we determined the coding-complete genome sequences of 99 bunyaviruses in the Centers for Disease Control and Prevention's Arbovirus Reference Collection, focusing on orthonairoviruses (family Nairoviridae), orthobunyaviruses (Peribunyaviridae), and phleboviruses (Phenuiviridae) that either completely or partially lacked genome sequences. These viruses had been collected over 66 years from 27 countries from vertebrates and arthropods representing 37 genera. Many of the viruses had been characterized serologically and through experimental infection of animals but were isolated in the pre-sequencing era. We took advantage of our unusually large sample size to systematically evaluate genomic characteristics of these viruses, including reassortment, and co-infection. We corroborated our findings using several independent molecular and virologic approaches, including Sanger sequencing of 197 genome segments, and plaque isolation of viruses from putative co-infected virus stocks. This study contributes to the described genetic diversity of bunyaviruses and will enhance the capacity to characterize emerging human pathogenic bunyaviruses. |
Socioeconomic patterns of smoking cessation behavior in low and middle-income countries: Emerging evidence from the Global Adult Tobacco Surveys and International Tobacco Control Surveys
Nargis N , Yong HH , Driezen P , Mbulo L , Zhao L , Fong GT , Thompson ME , Borland R , Palipudi KM , Giovino GA , Thrasher JF , Siahpush M . PLoS One 2019 14 (9) e0220223 INTRODUCTION: Tobacco smoking is often more prevalent among those with lower socio-economic status (SES) in high-income countries, which can be driven by the inequalities in initiation and cessation of smoking. Smoking is a leading contributor to socio-economic disparities in health. To date, the evidence for any socio-economic inequality in smoking cessation is lacking, especially in low- and middle-income countries (LMICs). This study examined the association between cessation behaviours and SES of smokers from eight LMICs. METHODS: Data among former and current adult smokers aged 18 and older came from contemporaneous Global Adult Tobacco Surveys (2008-2011) and the International Tobacco Control Surveys (2009-2013) conducted in eight LMICs (Bangladesh, Brazil, China, India, Mexico, Malaysia, Thailand and Uruguay). Adjusted odds ratios (AORs) of successful quitting in the past year by SES indicators (household income/wealth, education, employment status, and rural-urban residence) were estimated using multivariable logistic regression controlling for socio-demographics and average tobacco product prices. A random effects meta-analysis was used to combine the estimates of AORs pooled across countries and two concurrent surveys for each country. RESULTS: Estimated quit rates among smokers (both daily and occasional) varied widely across countries. Meta-analysis of pooled AORs across countries and data sources indicated that there was no clear evidence of an association between SES indicators and successful quitting. The only exception was employed smokers, who were less likely to quit than their non-employed counterparts, which included students, homemakers, retirees, and the unemployed (pooled AOR approximately 0.8, p<0.10). CONCLUSION: Lack of clear evidence of the impact of lower SES on adult cessation behaviour in LMICs suggests that lower-SES smokers are not less successful in their attempts to quit than their higher-SES counterparts. Specifically, lack of employment, which is indicative of younger age and lower nicotine dependence for students, or lower personal disposable income and lower affordability for the unemployed and the retirees, may be associated with quitting. Raising taxes and prices of tobacco products that lowers affordability of tobacco products might be a key strategy for inducing cessation behaviour among current smokers and reducing overall tobacco consumption. Because low-SES smokers are more sensitive to price increases, tobacco taxation policy can induce disproportionately larger decreases in tobacco consumption among them and help reduce socio-economic disparities in smoking and consequent health outcomes. |
Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats
Kading RC , Kityo RM , Mossel EC , Borland EM , Nakayiki T , Nalikka B , Nyakarahuka L , Ledermann JP , Panella NA , Gilbert AT , Crabtree MB , Peterhans JK , Towner JS , Amman BR , Sealy TK , Nichol ST , Powers AM , Lutwama JJ , Miller BR . Infect Ecol Epidemiol 2018 8 (1) 1439215 Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011-2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion: Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats (Epomophorus labiatus) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation. |
Zika virus disease-associated Guillain-Barre syndrome - Barranquilla, Colombia 2015-2016
Salinas JL , Walteros DM , Styczynski A , Garzon F , Quijada H , Bravo E , Chaparro P , Madero J , Acosta-Reyes J , Ledermann J , Arteta Z , Borland E , Burns P , Gonzalez M , Powers AM , Mercado M , Solano A , Sejvar JJ , Ospina ML . J Neurol Sci 2017 381 272-277 Background An outbreak of Guillain-Barre syndrome (GBS), a disorder characterized by acute, symmetric limb weakness with decreased or absent deep-tendon reflexes, was reported in Barranquilla, Colombia, after the introduction of Zika virus in 2015. We reviewed clinical data for GBS cases in Barranquilla and performed a case-control investigation to assess the association of suspect and probable Zika virus disease with GBS. Methods We used the Brighton Collaboration Criteria to confirm reported GBS patients in Barranquilla during October 2015-April 2016. In April 2016, two neighborhood and age range-matched controls were selected for each confirmed GBS case-patient. We obtained demographics and antecedent symptoms in the 2-month period before GBS onset for case-patients and the same period for controls. Sera were collected for Zika virus antibody testing. Suspected Zika virus disease was defined as a history of rash and >= 2 other Zika-related symptoms (fever, arthralgia, myalgia, or conjunctivitis). Probable Zika virus disease was defined as suspected Zika virus disease with laboratory evidence of a recent Zika virus or flavivirus infection. Conditional logistic regression adjusted for sex and race/ethnicity was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results We confirmed 47 GBS cases. Incidence increased with age (10-fold higher in those >= 60 years versus those < 20 years). We interviewed 40 case-patients and 79 controls. There was no significant difference in laboratory evidence of recent Zika virus or flavivirus infection between case-patients and controls (OR: 2.2; 95% CI: 0.9-5.1). GBS was associated with having suspected (OR: 3.0, 95% CI: 1.1-8.6) or probable Zika virus disease (OR: 4.6, CI: 1.1-19.0). Conclusions Older individuals and those with suspected and probable Zika virus disease had higher odds of developing GBS. Key points We confirmed a Guillain-Barre syndrome (GBS) outbreak in Barranquilla, Colombia, during October 2015-April 2016. A case-control investigation using neighborhood controls showed an association of suspected and probable Zika virus disease with GBS. |
Minimum infectious dose for chikungunya virus in Aedes aegypti and Ae. albopictus mosquitoes
Ledermann JP , Borland EM , Powers AM . Rev Panam Salud Publica 2017 41 e65 Understanding the ability of the chikungunya virus (CHIKV) to be transmitted by Aedes vectors in the Americas is critical for assessing epidemiological risk. One element that must be considered is the minimum infectious dose of virus that can lead to transmission following the extrinsic incubation period. This study aimed to determine the minimum infection rate for the two Aedes species studied. The results revealed that doses as low as 3.9 log10 plaque-forming units per mL (pfu/mL) of an Asian genotype CHIKV strain can lead to transmission by Ae. albopictus, and doses of at least 5.3 log10 pfu/mL from the same strain are needed for transmission from Ae. aegypti. These low infecting doses suggest that infected individuals may be infectious for almost the entire period of their viremia, and therefore, to prevent further cases, measures should be taken to prevent them from getting bitten by mosquitoes during this period. |
Arboviruses isolated from mosquitoes collected in Uganda, 2008-2012
Mossel EC , Crabtree MB , Mutebi JP , Lutwama JJ , Borland EM , Powers AM , Miller BR . J Med Entomol 2017 54 (5) 1403-1409 A large number of arthropod-borne viruses are endemic to East Africa. As a part of the process of undertaking a systematic characterization of the mosquito fauna of Uganda, we examined mosquitoes collected from 2008 through early 2012 for known and novel viruses. In all, 8,288 mosquito pools containing 157,554 mosquitoes were tested. Twenty-nine isolations of 11 different viruses were made from mosquitoes of nine distinct species and from pools identified only to genus Culex. Identified viruses were from family Togaviridae, alphaviruses Sindbis and Babanki viruses; family Rhabdoviridae, hapaviruses Mossuril and Kamese viruses; family Flaviviridae, flaviviruses West Nile and Usutu viruses; family Phenuiviridae, phlebovirus Arumowot virus; and family Peribunyaviridae, orthobunyaviruses Witwatersrand, Pongola, and Germiston viruses. In addition, a novel orthobunyavirus, provisionally named Mburo virus, was isolated from Coquillettidia metallica (Theobald). This is the first report of Babanki, Arumowot, and Mossuril virus isolation from Uganda. |
Increased rates of Guillain-Barre syndrome associated with Zika virus outbreak in the Salvador metropolitan area, Brazil
Styczynski AR , Malta JMAS , Krow-Lucal ER , Percio J , Nobrega ME , Vargas A , Lanzieri TM , Leite PL , Staples JE , Fischer MX , Powers AM , Chang GJ , Burns PL , Borland EM , Ledermann JP , Mossel EC , Schonberger LB , Belay EB , Salinas JL , Badaro RD , Sejvar JJ , Coelho GE . PLoS Negl Trop Dis 2017 11 (8) e0005869 In mid-2015, Salvador, Brazil, reported an outbreak of Guillain-Barre 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. |
Dengue and West Nile virus transmission in children and adults in coastal Kenya
Vu DM , Banda T , Teng CY , Heimbaugh C , Muchiri EM , Mungai PL , Mutuku FM , Brichard J , Gildengorin G , Borland EM , Powers AM , Kitron U , King CH , LaBeaud AD . Am J Trop Med Hyg 2016 96 (1) 141-143 Dengue virus (DENV) and West Nile virus (WNV) are important reemerging arboviruses that are under-recognized in many parts of Africa due to lack of surveillance. As a part of a study on flavivirus, alphavirus, and parasite exposure in coastal Kenya, we measured neutralizing antibody against DENV and, to evaluate assay specificity, WNV in serum samples that tested positive for serum anti-DENV IgG by enzyme-linked immunosorbent assay. Of 830 anti-DENV IgG-positive samples that were tested for neutralizing activity, 488 (58.8%) neutralized DENV and 94 (11.3%) neutralized WNV. Of children ≤ 10 years of age, 23% and 17% had serum neutralizing antibody to DENV and WNV, respectively, indicating that DENV and WNV transmission has occurred in this region within the past decade. The results suggest that ongoing DENV and WNV transmission continues on the coast of Kenya and supports a need for routine arboviral surveillance in the area to detect and respond to future outbreaks. |
Culex Tarsalis Mosquitoes as Vectors of Highlands J Virus.
Borland EM , Ledermann JP , Powers AM . Vector Borne Zoonotic Dis 2016 16 (8) 558-65 Highlands J virus (HJV) is an alphavirus closely related to western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV). HJV is an avian pathogen with the potential for disruption of poultry operations, but is not known to cause human or equine disease. HJV has only been identified in the eastern United States and is thought to have a transmission cycle similar to that of EEEV involving Culiseta melanura mosquitoes and birds. However, HJV is more genetically similar to WEEV and it remains unclear if it may be transmitted by Culex species mosquitoes like WEEV. Seven strains of HJV were characterized to assess this potential. Phylogenetic analysis of whole genome sequences revealed four distinct HJV lineages (lineages 1-4), and vector competence studies in Cx. tarsalis with four of the HJV strains from different lineages yielded two distinct infection patterns. Lineage 1 strains had low infection rates, while lineages 2 and 4 had significantly higher infection rates similar to those previously published for WEEV. The average mosquito body viral titer was highest at 8 dpi (6.60-7.26 log10 pfu equivalents/body), and head titers at all time points ranged between 6.01 and 6.80 log10 pfu equivalents/head. Nearly 45% of mosquitoes infected with strain AB-80-9 were able to transmit virus in saliva with an average titer of 5.02 log10 pfu equivalents/saliva. A single amino acid difference between high and low infectivity phenotypes was identified at genome position 8605, in the E2 gene. A nonpolar glycine was present in the low infectivity lineage 1 strains, while an acidic glutamic acid was present in the higher infectivity lineage 2 and 4 strains. This study demonstrates HJV transmission by Cx. tarsalis mosquitoes and clearly identifies the potential for transmission in the western United States. Two infection phenotypes were exhibited, indicating the need for further studies to understand Culex species transmission patterns. |
High rates of o'nyong nyong and Chikungunya virus transmission in coastal Kenya
LaBeaud AD , Banda T , Brichard J , Muchiri EM , Mungai PL , Mutuku FM , Borland E , Gildengorin G , Pfeil S , Teng CY , Long K , Heise M , Powers AM , Kitron U , King CH . PLoS Negl Trop Dis 2015 9 (2) e0003436 BACKGROUND: Chikungunya virus (CHIKV) and o'nyong nyong virus (ONNV) are mosquito-borne alphaviruses endemic in East Africa that cause acute febrile illness and arthritis. The objectives of this study were to measure the seroprevalence of CHIKV and ONNV in coastal Kenya and link it to demographics and other risk factors. METHODOLOGY: Demographic and exposure questionnaires were administered to 1,848 participants recruited from two village clusters (Milalani-Nganja and Vuga) in 2009. Sera were tested for alphavirus exposure using standardized CHIKV IgG ELISA protocols and confirmed with plaque reduction neutralization tests (PRNT). Logistic regression models were used to determine the variables associated with seropositivity. Weighted K test for global clustering of houses with alphavirus positive participants was performed for distance ranges of 50-1,000 meters, and G* statistic and kernel density mapping were used to identify locations of higher seroprevalence. PRINCIPAL FINDINGS: 486 (26%) participants were seropositive by IgG ELISA. Of 443 PRNT confirmed positives, 25 samples (6%) were CHIKV+, 250 samples (56%) were ONNV+, and 168 samples (38%) had high titers for both. Age was significantly associated with seropositivity (OR 1.01 per year, 95% C.I. 1.00-1.01); however, younger adults were more likely to be seropositive than older adults. Males were less likely to be seropositive (p<0.05; OR 0.79, 95% C.I. 0.64-0.97). Adults who owned a bicycle (p<0.05; OR 1.37, 95% C.I. 1.00-1.85) or motor vehicle (p<0.05; OR 4.64, 95% C.I. 1.19-18.05) were more likely to be seropositive. Spatial analysis demonstrated hotspots of transmission within each village and clustering among local households in Milalani-Nganja, peaking at the 200-500m range. CONCLUSIONS/SIGNIFICANCE: Alphavirus exposure, particularly ONNV exposure, is common in coastal Kenya with ongoing interepidemic transmission of both ONNV and CHIKV. Women and adults were more likely to be seropositive. Household location may be a defining factor for the ecology of alphaviral transmission in this region. |
2014 Consensus Statement from the first Economics of Physical Inactivity Consensus (EPIC) conference (Vancouver)
Davis JC , Verhagen E , Bryan S , Liu-Ambrose T , Borland J , Buchner D , Hendriks MR , Weiler R , Morrow JR Jr , van Mechelen W , Blair SN , Pratt M , Windt J , Al-Tunaiji H , Macri E , Khan KM . Br J Sports Med 2014 48 (12) 947-51 This article describes major topics discussed from the 'Economics of Physical Inactivity Consensus Workshop' (EPIC), held in Vancouver, Canada, in April 2011. Specifically, we (1) detail existing evidence on effective physical inactivity prevention strategies; (2) introduce economic evaluation and its role in health policy decisions; (3) discuss key challenges in establishing and building health economic evaluation evidence (including accurate and reliable costs and clinical outcome measurement) and (4) provide insight into interpretation of economic evaluations in this critically important field. We found that most methodological challenges are related to (1) accurately and objectively valuing outcomes; (2) determining meaningful clinically important differences in objective measures of physical inactivity; (3) estimating investment and disinvestment costs and (4) addressing barriers to implementation. We propose that guidelines specific for economic evaluations of physical inactivity intervention studies are developed to ensure that related costs and effects are robustly, consistently and accurately measured. This will also facilitate comparisons among future economic evidence. |
Sunguru virus: a novel virus in the family Rhabdoviridae isolated from a chicken in north-western Uganda.
Ledermann JP , Zeidner N , Borland EM , Mutebi JP , Lanciotti RS , Miller BR , Lutwama JJ , Tendo JM , Andama V , Powers AM . J Gen Virol 2014 95 1436-1443 Sunguru virus (SUNV), a novel virus belonging to the highly diverse Rhabdoviridae family, was isolated from a domestic chicken in the district of Arua, Uganda in 2011. This is the first documented isolation of a rhabdovirus from a chicken. SUNV is related to, but distinct from, Boteke virus and other members of the unclassified Sandjimba group. The genome is 11,056 kb in length and contains the five core rhabdovirus genes plus an additional C gene (within the open reading frame of the phosphoprotein gene) and a small hydrophobic protein (between the matrix and glycoprotein genes). Inoculation of vertebrate cells resulted in significant growth, with a peak titer of 7.8 log10 PFU/mL observed in baby hamster kidney cells. Little to no growth was observed in invertebrate cells and in live mosquitoes, with Anopheles gambiae mosquitoes demonstrating a 47.4% infection rate in the body but no dissemination to the salivary glands; this suggests that this novel virus is not arthropod-borne like some other members of the family Rhabdoviridae. |
Prevalence of antibodies to alphaviruses and flaviviruses in free-ranging game animals and nonhuman primates in the greater Congo basin
Kading RC , Borland EM , Cranfield M , Powers AM . J Wildl Dis 2013 49 (3) 587-99 Vector-borne and zoonotic pathogens have comprised a significant proportion of the emerging infectious diseases in humans in recent decades. The role of many wildlife species as reservoirs for arthropod-borne viral pathogens is poorly understood. We investigated the exposure history of various African wildlife species from the Congo basin to mosquito-borne flaviviruses and alphaviruses by testing archived serum samples. Sera from 24 African forest buffalo (Syncerus caffer nanus), 34 African elephants (Loxodonta africana), 40 duikers (Cephalophus and Philantomba spp.), 25 mandrills (Mandrillus sphinx), 32 mountain gorillas (Gorilla beringei beringei), five Grauer's gorillas (Gorilla beringei graueri), two L'Hoest's monkeys (Cercopithecus lhoesti), two golden monkeys (Cercopithecus kandti), and three chimpanzees (Pan troglodytes) sampled between 1991 and 2009 were tested for antibodies against chikungunya virus (CHIKV), o'nyong-nyong virus (ONNV), West Nile virus (WNV), dengue 2 virus (DENV-2), and yellow fever virus (YFV) by plaque reduction neutralization test. Specific neutralizing antibodies against ONNV were found in African forest buffalo in the Democratic Republic of the Congo (DRC) and Gabon, duikers in the DRC, and mandrills in Gabon, providing novel evidence of enzootic circulation of ONNV in these countries. African forest buffalo in the DRC and Gabon also demonstrated evidence of exposure to CHIKV, WNV, and DENV-2, while mandrills in Gabon were antibody positive for CHIKV, DENV-2, WNV, and YFV. All of the elephants tested had a strong neutralizing antibody response to WNV. We also document results from a survey of gorillas for arboviruses, of which 4/32 (13%) had antibody to an alphavirus or flavivirus. Overall, our results demonstrate a high prevalence of neutralizing antibodies against multiple arboviruses in wildlife in equatorial Africa. |
Molecular determinants of mouse neurovirulence and mosquito infection for Western equine encephalitis virus
Mossel EC , Ledermann JP , Phillips AT , Borland EM , Powers AM , Olson KE . PLoS One 2013 8 (3) e60427 Western equine encephalitis virus (WEEV) is a naturally occurring recombinant virus derived from ancestral Sindbis and Eastern equine encephalitis viruses. We previously showed that infection by WEEV isolates McMillan (McM) and IMP-181 (IMP) results in high ( approximately 90-100%) and low (0%) mortality, respectively, in outbred CD-1 mice when virus is delivered by either subcutaneous or aerosol routes. However, relatively little is known about specific virulence determinants of WEEV. We previously observed that IMP infected Culex tarsalis mosquitoes at a high rate (app. 80%) following ingestion of an infected bloodmeal but these mosquitoes were infected by McM at a much lower rate (10%). To understand the viral role in these phenotypic differences, we characterized the pathogenic phenotypes of McM/IMP chimeras. Chimeras encoding the E2 of McM on an IMP backbone (or the reciprocal) had the most significant effect on infection phenotypes in mice or mosquitoes. Furthermore, exchanging the arginine, present on IMP E2 glycoprotein at position 214, for the glutamine present at the same position on McM, ablated mouse mortality. Curiously, the reciprocal exchange did not confer mouse virulence to the IMP virus. Mosquito infectivity was also determined and significantly, one of the important loci was the same as the mouse virulence determinant identified above. Replacing either IMP E2 amino acid 181 or 214 with the corresponding McM amino acid lowered mosquito infection rates to McM-like levels. As with the mouse neurovirulence, reciprocal exchange of amino acids did not confer mosquito infectivity. The identification of WEEV E2 amino acid 214 as necessary for both IMP mosquito infectivity and McM mouse virulence indicates that they are mutually exclusive phenotypes and suggests an explanation for the lack of human or equine WEE cases even in the presence of active transmission. |
O'nyong nyong virus molecular determinants of unique vector specificity reside in non-structural protein 3
Saxton-Shaw KD , Ledermann JP , Borland EM , Stovall JL , Mossel EC , Singh AJ , Wilusz J , Powers AM . PLoS Negl Trop Dis 2013 7 (1) e1931 O'nyong nyong virus (ONNV) and Chikungunya virus (CHIKV) are two closely related alphaviruses with very different infection patterns in the mosquito, Anopheles gambiae. ONNV is the only alphavirus transmitted by anopheline mosquitoes, but specific molecular determinants of infection of this unique vector specificity remain unidentified. Fifteen distinct chimeric viruses were constructed to evaluate both structural and non-structural regions of the genome and infection patterns were determined through artificial infectious feeds in An. gambiae with each of these chimeras. Only one region, non-structural protein 3 (nsP3), was sufficient to up-regulate infection to rates similar to those seen with parental ONNV. When ONNV non-structural protein 3 (nsP3) replaced nsP3 from CHIKV virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%. No other single gene or viral region addition was able to restore infection rates. Thus, we have shown that a non-structural genome element involved in viral replication is a major element involved in ONNV's unique vector specificity. |
Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism
Plante K , Wang E , Partidos CD , Weger J , Gorchakov R , Tsetsarkin K , Borland EM , Powers AM , Seymour R , Stinchcomb DT , Osorio JE , Frolov I , Weaver SC . PLoS Pathog 2011 7 (7) e1002142 Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES) from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus. |
Probing the attenuation and protective efficacy of a candidate chikungunya virus vaccine in mice with compromised interferon (IFN) signaling
Partidos CD , Weger J , Brewoo J , Seymour R , Borland EM , Ledermann JP , Powers AM , Weaver SC , Stinchcomb DT , Osorio JE . Vaccine 2011 29 (16) 3067-73 Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes explosive outbreaks of febrile illness associated with rash, and painful arthralgia. The CHIK vaccine strain 181/clone25 (181/25) developed by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) was shown to be well-tolerated and highly immunogenic in phase I and II clinical trials although it induced transient arthralgia in some healthy adult volunteers. In an attempt to better understand the host factors that are involved in the attenuating phenotype of CHIK 181/25 vaccine virus we conducted studies in interferon (IFN)-compromised mice and also evaluated its immunogenic potential and protective capacity. Infection of AG129 mice (defective in IFN-alpha/beta and IFN-gamma receptor signaling) with CHIK 181/25 resulted in rapid mortality within 3-4 days. In contrast, all infected A129 mice (defective in IFN-alpha/beta receptor signaling) survived with temporary morbidity characterized by ruffled appearance and body weight loss. A129 heterozygote mice that retain partial IFN-alpha/beta receptor signaling activity remained healthy. Infection of A129 mice with CHIK 181/25 induced significant levels of IFN-gamma and IL-12 while the inflammatory cytokines, TNFalpha and IL-6 remained low. A single administration of the CHIK 181/25 vaccine provided both short-term and long-term protection (38 days and 247 days post-prime, respectively) against challenge with wt CHIKV-La Reunion (CHIKV-LR). This protection was at least partially mediated by antibodies since passively transferred immune serum protected both A129 and AG129 mice from wt CHIKV-LR and 181/25 virus challenge. Overall, these data highlight the importance of IFNs in controlling CHIK 181/25 vaccine and demonstrate the ability of this vaccine to elicit neutralizing antibody responses that confer short-and long-term protection against wt CHIKV-LR challenge. |
Obesity prevalence among low-income, preschool-aged children - United States, 1998-2008
Sharma AJ , Grummer-Strawn LM , Dalenius K , Galuska D , Anandappa M , Borland E , Mackintosh H , Smith R . MMWR Morb Mortal Wkly Rep 2009 58 (28) 769-73 Childhood obesity continues to be a leading public health concern that disproportionately affects low-income and minority children. Children who are obese in their preschool years are more likely to be obese in adolescence and adulthood and to develop diabetes, hypertension, hyperlipidemia, asthma, and sleep apnea. One of the Healthy People 2010 objectives (19-3) is to reduce to 5% the proportion of children and adolescents who are obese. CDC's Pediatric Nutrition Surveillance System (PedNSS) is the only source of nationally compiled obesity surveillance data obtained at the state and local level for low-income, preschool-aged children participating in federally funded health and nutrition programs. To describe progress in reducing childhood obesity, CDC examined trends and current prevalence in obesity using PedNSS data submitted by participating states, territories, and Indian tribal organizations during 1998-2008. The findings indicated that obesity prevalence among low-income, preschool-aged children increased steadily from 12.4% in 1998 to 14.5% in 2003, but subsequently remained essentially the same, with a 14.6% prevalence in 2008. Reducing childhood obesity will require effective prevention strategies that focus on environments and policies promoting physical activity and a healthy diet for families, child care centers, and communities. |
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