Last data update: Mar 21, 2025. (Total: 48935 publications since 2009)
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Dengue outbreak and response - Puerto Rico, 2024
Ware-Gilmore F , Rodriguez DM , Ryff Mph K , Torres JM , Velez MP , Torres-Toro CT , Santiago GA , Rivera A , Madewell ZJ , Maldonado Y , Cardona-Gerena I , Brown GC , Adams LE , Paz-Bailey G , Marzán-Rodriguez M . MMWR Morb Mortal Wkly Rep 2025 74 (5) 54-60 ![]() ![]() Dengue, a mosquitoborne viral infection, is a public health threat in Puerto Rico, where multiple dengue virus (DENV) serotypes circulate. Dengue causes an acute febrile illness that can progress to severe disease or death. The last outbreak declared by the Puerto Rico Department of Health occurred during 2013. In January 2024, the number of dengue cases in Puerto Rico surpassed the epidemic threshold and remained elevated, prompting the Puerto Rico Department of Health to declare a public health emergency in March 2024. In collaboration with CDC, a dengue outbreak response was initiated to monitor the outbreak and implement vector-control measures alongside public health campaigns to raise awareness about increasing dengue case numbers and strategies to prevent mosquito bites. During 2024, a total of 6,291 confirmed dengue cases were reported; the highest numbers of cases were reported in the municipalities of San Juan (1,200; 17.3%), Carolina (354; 5.1%), and Rincón (252; 3.6%). DENV serotype 3 predominated, accounting for 59.2% of cases with known serotype. Approximately one half of ill patients (52.3%) required hospitalization, with the highest percentages of hospitalizations (33.9%) and severe dengue cases (28.4%) occurring among persons aged 10-19 years. Overall, severe dengue was identified in 4.2% of cases, with 11 reported fatalities (0.2%). Transmission remains elevated in multiple regions, underscoring the need for tailored public health measures, including vaccination among eligible populations, vector management, community outreach, and provider education to facilitate improved outcomes. To reduce the risk for mosquito bites, residents of and visitors to Puerto Rico should consider using repellents, wearing protective clothing, and staying in places with door and window screens. |
The Human Phenotype Ontology in 2024: phenotypes around the world
Gargano MA , Matentzoglu N , Coleman B , Addo-Lartey EB , Anagnostopoulos AV , Anderton J , Avillach P , Bagley AM , Bakštein E , Balhoff JP , Baynam G , Bello SM , Berk M , Bertram H , Bishop S , Blau H , Bodenstein DF , Botas P , Boztug K , Čady J , Callahan TJ , Cameron R , Carbon SJ , Castellanos F , Caufield JH , Chan LE , Chute CG , Cruz-Rojo J , Dahan-Oliel N , Davids JR , de Dieuleveult M , de Souza V , de Vries BBA , de Vries E , DePaulo JR , Derfalvi B , Dhombres F , Diaz-Byrd C , Dingemans AJM , Donadille B , Duyzend M , Elfeky R , Essaid S , Fabrizzi C , Fico G , Firth HV , Freudenberg-Hua Y , Fullerton JM , Gabriel DL , Gilmour K , Giordano J , Goes FS , Moses RG , Green I , Griese M , Groza T , Gu W , Guthrie J , Gyori B , Hamosh A , Hanauer M , Hanušová K , He YO , Hegde H , Helbig I , Holasová K , Hoyt CT , Huang S , Hurwitz E , Jacobsen JOB , Jiang X , Joseph L , Keramatian K , King B , Knoflach K , Koolen DA , Kraus ML , Kroll C , Kusters M , Ladewig MS , Lagorce D , Lai MC , Lapunzina P , Laraway B , Lewis-Smith D , Li X , Lucano C , Majd M , Marazita ML , Martinez-Glez V , McHenry TH , McInnis MG , McMurry JA , Mihulová M , Millett CE , Mitchell PB , Moslerová V , Narutomi K , Nematollahi S , Nevado J , Nierenberg AA , Čajbiková NN , Nurnberger JI Jr , Ogishima S , Olson D , Ortiz A , Pachajoa H , Perez de Nanclares G , Peters A , Putman T , Rapp CK , Rath A , Reese J , Rekerle L , Roberts AM , Roy S , Sanders SJ , Schuetz C , Schulte EC , Schulze TG , Schwarz M , Scott K , Seelow D , Seitz B , Shen Y , Similuk MN , Simon ES , Singh B , Smedley D , Smith CL , Smolinsky JT , Sperry S , Stafford E , Stefancsik R , Steinhaus R , Strawbridge R , Sundaramurthi JC , Talapova P , Tenorio Castano JA , Tesner P , Thomas RH , Thurm A , Turnovec M , van Gijn ME , Vasilevsky NA , Vlčková M , Walden A , Wang K , Wapner R , Ware JS , Wiafe AA , Wiafe SA , Wiggins LD , Williams AE , Wu C , Wyrwoll MJ , Xiong H , Yalin N , Yamamoto Y , Yatham LN , Yocum AK , Young AH , Yüksel Z , Zandi PP , Zankl A , Zarante I , Zvolský M , Toro S , Carmody LC , Harris NL , Munoz-Torres MC , Danis D , Mungall CJ , Köhler S , Haendel MA , Robinson PN . Nucleic Acids Res 2023 52 D1333-D1346 ![]() ![]() The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs. |
Genomic analysis, immunomodulation and deep phenotyping of patients with nodding syndrome.
Soldatos A , Nutman TB , Johnson T , Dowell SF , Sejvar JJ , Wilson MR , DeRisi JL , Inati SK , Groden C , Evans C , O'Connell EM , Toliva BO , Aceng JR , Aryek-Kwe J , Toro C , Stratakis CA , Buckler AG , Cantilena C , Palmore TN , Thurm A , Baker EH , Chang R , Fauni H , Adams D , Macnamara EF , Lau CC , Malicdan MCV , Pusey-Swerdzewski B , Downing R , Bunga S , Thomas JD , Gahl WA , Nath A . Brain 2022 146 (3) 968-976 ![]() The etiology of Nodding Syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with Nodding Syndrome, investigate potential contributors to disease etiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for Nodding Syndrome and with a conducive family structure for genomic analyses. Of the eight family members who participated in the study at the National Institutes of Health (NIH) Clinical Center, three had Nodding Syndrome. The three affected patients were extensively evaluated with metagenomic sequencing for infectious pathogens, exome sequencing, spinal fluid immune analyses, neurometabolic and toxicology testing, continuous electroencephalography, and neuroimaging. Five unaffected family members underwent a subset of testing for comparison. A distinctive interictal pattern of sleep-activated bursts of generalized and multifocal epileptiform discharges and slowing was observed in two patients. Brain imaging showed two patients had mild generalized cerebral atrophy, and both patients and unaffected family members had excessive metal deposition in the basal ganglia. Trace metal biochemical evaluation was normal. Cerebrospinal fluid (CSF) was non-inflammatory, and one patient had CSF-restricted oligoclonal bands. Onchocerca volvulus specific antibodies were present in all patients and skin snips were negative for active onchocerciasis. Metagenomic sequencing of serum and CSF revealed hepatitis B virus in the serum of one patient. Vitamin B6 metabolites were borderline low in all family members, and CSF pyridoxine metabolites were normal. Mitochondrial DNA testing was normal. Exome sequencing did not identify potentially causal candidate gene variants. Nodding Syndrome is characterized by a distinctive pattern of sleep-activated epileptiform activity. The associated growth stunting may be due to hypothalamic dysfunction. Extensive testing years after disease onset did not clarify a causal etiology. A trial of immunomodulation (plasmapheresis in two patients and intravenous immunoglobulin in one patient) was given without short-term effect, but longer-term follow-up was not possible to fully assess any benefit of this intervention. |
Rabies surveillance in the United States during 2020
Ma X , Bonaparte S , Toro M , Orciari LA , Gigante CM , Kirby JD , Chipman RB , Fehlner-Gardiner C , Cedillo VG , Aréchiga-Ceballos N , Rao AK , Petersen BW , Wallace RM . J Am Vet Med Assoc 2022 260 (10) 1-9 OBJECTIVE: To provide epidemiological information on animal and human cases of rabies in the US during 2020 and summaries of 2020 rabies surveillance for Canada and Mexico. ANIMALS: All animals submitted for laboratory diagnosis of rabies in the US during 2020. PROCEDURES: State and territorial public health departments and USDA Wildlife Services provided 2020 rabies surveillance data. Data were analyzed temporally and geographically to assess trends in domestic and wildlife rabies cases. RESULTS: During 2020, 54 jurisdictions submitted 87,895 animal samples for rabies testing, of which 85,483 (97.3%) had a conclusive (positive or negative) test result. Of these, 4,479 (5.2%) tested positive for rabies, representing a 4.5% decrease from the 4,690 cases reported in 2019. Texas (n = 580 [12.9%]), Pennsylvania (371 [8.3%]), Virginia (351 [7.8%]), New York (346 [7.7%]), North Carolina (301 [6.7%]), New Jersey (257 [5.7%]), Maryland (256 [5.7%]), and California (248 [5.5%]) together accounted for > 60% of all animal rabies cases reported in 2020. Of the total reported rabid animals, 4,090 (91.3%) involved wildlife, with raccoons (n = 1,403 [31.3%]), bats (1,400 [31.3%]), skunks (846 [18.9%]), and foxes (338 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (288 [6.4%]), cattle (43 [1.0%]), and dogs (37 [0.8%]) accounted for 95% of rabies cases involving domestic animals in 2020. No human rabies cases were reported in 2020. CONCLUSIONS AND CLINICAL RELEVANCE: For the first time since 2006, the number of samples submitted for rabies testing in the US was < 90,000; this is thought to be due to factors related to the COVID-19 pandemic, as similar decreases in sample submission were also reported by Canada and Mexico. |
Cemeteries as sources of Aedes aegypti and other mosquito species in southeastern Puerto Rico
Otero LM , Medina-Martinez G , Seplveda M , Acevedo V , Toro M , Barrera R . Trop Med Int Health 2022 27 (3) 300-309 OBJECTIVE: To investigate the presence and abundance of mosquito species in containers found in different types of cemeteries in Puerto Rico to assess their importance and make control recommendations. METHODS: We conducted surveys of containers with water in 16 cemeteries in southeastern Puerto Rico to: detect the presence of larvae and pupae of Aedes aegypti and other mosquitoes; identify the most common and productive containers and study their variation in relation to the type of cemetery. RESULTS: The most common containers with water were flowerpots, followed in abundance by a variety of discarded containers and open tombs. We found a positive relationship between density of containers with water and rainfall. There was a rich community of mosquito species developing in containers of the inspected cemeteries: nine mosquito species belonging to four genera with Ae. aegypti and Ae. mediovittatus being the most frequent and abundant. We sampled 13 cement type cemeteries, 2 mixed, and only 1 lawn cemetery, consequently we could not draw any conclusion regarding container productivity and cemetery type. CONCLUSIONS: Surveyed cemeteries were important sources of Ae. aegypti and other mosquitoes in flowerpots, discarded containers, and open tombs. We recommend conducting further studies to establish how frequently inspections should occur; and mosquito control by emptying aquatic habitats and larviciding to reduce mosquito productivity and protect workers and visitors from mosquito bites and possible transmission of arboviruses. |
Patterns of wasting among pregnant and lactating women in Uganda, 2015-2018: analysis of Nutrition surveillance data
Kyamwine IB , Namukose S , Wibabara Y , Bulage L , Kwesiga B , Ario AR , Harris JR . BMC Nutr 2021 7 (1) 59 BACKGROUND: Maternal nutrition is closely linked to the survival and development of children during the first 1000 days of life. Maternal wasting, a measure of malnutrition, is measured using the mid-upper arm circumference. However, in 2019, the rate and distribution of wasting among pregnant and lactating women was not known. We described annual trends and distribution of wasting among pregnant and lactating women (PLW), Uganda, 2015-2018, to inform programming on targeted nutritional interventions. METHODS: We analyzed nutrition surveillance data from the District Health Information System for all PLW from 2015 to 2018. We used the World Health Organization standard thresholds to determine wasting among PLW by year and region, drawing choropleth maps to demonstrate the geographic distribution of wasting among PLW. We used logistic regression to assess wasting trends. RESULTS: During 2015-2018, 268,636 PLW were wasted (prevalence = 5.5%). Of the 15 regions of Uganda, Karamoja (prevalence = 21%) and Lango (prevalence = 17%) registered the highest prevalence while Toro (prevalence = 2.7%) and Kigezi (prevalence = 2.0%) registered the lowest prevalence. The national annual prevalence of wasting among PLW declined by 31% from 2015 to 2018 (OR = 0.69, p < 0.001). Regions in the north had increasing trends of wasting over the period [Lango (OR = 1.6, p < 0.001) and Acholi (OR = 1.2, p < 0.001)], as did regions in the east [(Bugisu (OR = 3.4, p < 0.001), Bukedi (OR = 1.4, p < 0.001), and Busoga (OR = 1.3, p < 0.001)]. The other 11 regions showed declines. CONCLUSION: The trend of wasting among PLW nationally declined during the study period. Lango and Acholi regions, both of which were experiencing a nutrition state of emergency during this period, had both high and rising rates of wasting, as did the Karamoja region, which experienced the highest wasting rates. We recommended that the Ministry of Health increases its focus on nutrition monitoring for PLW and conduct an analysis to clearly identify the factors underlying malnutrition specific for PLW in these regions. |
Notes from the Field: COVID-19 Prevention Practices in State Prisons - Puerto Rico, 2020.
Davlantes E , Toro M , Villalobos R , Sanchez-Gonzalez L . MMWR Morb Mortal Wkly Rep 2020 69 (33) 1144 As of August 17, 2020, the Puerto Rico Department of Health had reported 11,723 confirmed cases of coronavirus disease 2019 (COVID-19), 15,037 probable cases, and 335 deaths. Among persons incarcerated in state prisons, a high-risk congregate setting, only two COVID-19 cases and no associated deaths had been reported* (1). These results followed implementation in mid-March of a protocol (2) for the diagnosis, management, and prevention of COVID-19 in all Puerto Rico Department of Correction and Rehabilitation prisons based on CDC’s interim guidance on management of COVID-19 in correctional and detention facilities (3). The protocol featured wide-ranging measures, from visitor restrictions to enhanced cleaning; this report focuses specifically on COVID-19 mitigation measures directed toward incarcerated persons. |
Characteristics of Persons Who Died with COVID-19 - United States, February 12-May 18, 2020.
Wortham JM , Lee JT , Althomsons S , Latash J , Davidson A , Guerra K , Murray K , McGibbon E , Pichardo C , Toro B , Li L , Paladini M , Eddy ML , Reilly KH , McHugh L , Thomas D , Tsai S , Ojo M , Rolland S , Bhat M , Hutchinson K , Sabel J , Eckel S , Collins J , Donovan C , Cope A , Kawasaki B , McLafferty S , Alden N , Herlihy R , Barbeau B , Dunn AC , Clark C , Pontones P , McLafferty ML , Sidelinger DE , Krueger A , Kollmann L , Larson L , Holzbauer S , Lynfield R , Westergaard R , Crawford R , Zhao L , Bressler JM , Read JS , Dunn J , Lewis A , Richardson G , Hand J , Sokol T , Adkins SH , Leitgeb B , Pindyck T , Eure T , Wong K , Datta D , Appiah GD , Brown J , Traxler R , Koumans EH , Reagan-Steiner S . MMWR Morb Mortal Wkly Rep 2020 69 (28) 923-929 During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City). |
Lessons from the reestablishment of Public Health Laboratory activities in Puerto Rico after Hurricane Maria
Hardy MC , Stinnett RC , Kines KJ , Rivera-Nazario DM , Lowe DE , Mercante AM , Gonzalez Jimenez N , Cuevas Ruiz RI , Rivera Arbolay HI , Gonzalez Pena RL , Toro M , Trujillo AA , Pappas CL , Llewellyn AC , Candal F , Burgos Garay M , Gomez GA , Concepcion Acevedo J , Ansbro M , Moura H , Shaw MW , Muehlenbachs A , Romanoff LC , Sunshine BJ , Rose DA , Patel A , Shapiro CN , Luna-Pinto SC , Pillai SK , O'Neill E . Nat Commun 2019 10 (1) 2720 Public Health Laboratories (PHLs) in Puerto Rico did not escape the devastation caused by Hurricane Maria. We implemented a quality management system (QMS) approach to systematically reestablish laboratory testing, after evaluating structural and functional damage. PHLs were inoperable immediately after the storm. Our QMS-based approach began in October 2017, ended in May 2018, and resulted in the reestablishment of 92% of baseline laboratory testing capacity. Here, we share lessons learned from the historic recovery of the largest United States' jurisdiction to lose its PHL capacity, and provide broadly applicable tools for other jurisdictions to enhance preparedness for public health emergencies. |
Factors associated with accuracy of self-assessment compared with tested non-English language proficiency among primary care providers
Diamond L , Toro Bejarano M , Chung S , Ferguson W , Gonzalez J , Genoff Garzon M , Mujawar I , Gany F . Med Care 2019 57 (5) 385-390 BACKGROUND: There are no accepted best practices for clinicians to report their non-English language (NEL) fluencies. Language discordance between patients with limited English proficiency and their clinicians may contribute to suboptimal quality of care. OBJECTIVES: To compare self-assessed clinician NEL proficiency with a validated oral language proficiency test. To identify clinician characteristics associated with self-assessment accuracy. SUBJECTS: Primary care providers from California and Massachusetts. RESEARCH DESIGN: We surveyed 98 clinicians about demographics and their NEL self-assessment using an adapted version of the Interagency Language Roundtable (ILR) scale followed by an oral proficiency interview: The Clinician Cultural and Linguistic Assessment (CCLA). We compared the ILR to the CCLA and analyzed factors associated with the accuracy of self-assessment. RESULTS: Ninety-eight primary care providers participated: 75.5% were women, 62.2% were white, and Spanish was the most common NEL reported (81.6%). The average CCLA score was 78/100 with a 70% passing-rate. There was a moderate correlation between the ILR and CCLA (0.512; P<0.0001). Participants whose self-reported levels were "fair" and "poor" had a 0% pass-rate and 100% who self-reported "excellent" passed the CCLA. Middle ILR levels showed a wider variance. Clinicians who reported a NEL other than Spanish and whose first language was not English were more likely to accurately self-assess their abilities. CONCLUSIONS: Self-assessment showed a moderate correlation with the validated CCLA test. Additional testing may be required for clinicians at the middle levels. Clinicians whose native languages were not English and those using languages other than Spanish with patients may be more accurate in their self-assessment. |
Initial public health laboratory response after Hurricane Maria - Puerto Rico, 2017
Concepcion-Acevedo J , Patel A , Luna-Pinto C , Pena RG , Cuevas Ruiz RI , Arbolay HR , Toro M , Deseda C , De Jesus VR , Ribot E , Gonzalez JQ , Rao G , De Leon Salazar A , Ansbro M , White BB , Hardy MC , Georgi JC , Stinnett R , Mercante AM , Lowe D , Martin H , Starks A , Metchock B , Johnston S , Dalton T , Joglar O , Stafford C , Youngblood M , Klein K , Lindstrom S , Berman L , Galloway R , Schafer IJ , Walke H , Stoddard R , Connelly R , McCaffery E , Rowlinson MC , Soroka S , Tranquillo DT , Gaynor A , Mangal C , Wroblewski K , Muehlenbachs A , Salerno RM , Lozier M , Sunshine B , Shapiro C , Rose D , Funk R , Pillai SK , O'Neill E . MMWR Morb Mortal Wkly Rep 2018 67 (11) 333-336 Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services. |
The epidemiology of syphilis in New York City; historic trends and the current outbreak among men who have sex with men, 2016
Schillinger JA , Slutsker JS , Pathela P , Klingler E , Hennessy RR , Toro B , Blank S . Sex Transm Dis 2018 45 S48-S54 BACKGROUND: Male primary and secondary (P&S) and early latent (EL) syphilis cases have increased markedly in New York City (NYC) after a historic nadir in 1998. The majority of cases are among men-who-have-sex-with-men (MSM). We describe the epidemiology of syphilis among NYC males to provide a model of how one jurisdiction collects, analyzes, interprets, uses, and disseminates local data to guide programmatic activities directed at syphilis control. METHODS: We analyzed trends in reported infectious syphilis cases using routinely collected surveillance and case investigation data. HIV co-infection status was ascertained by routine deterministic match between sexually transmitted infection and HIV surveillance registries, and self-report. We mapped diagnosing facilities to display the relative contribution of different public/private facilities. Characteristics of male syphilis cases diagnosed in public sexual health (SH) clinics were compared to those diagnosed elsewhere. RESULTS: During 2012-2016, male P&S syphilis case rates increased 81%, from 24.8 to 44.8/100,000 (1832 cases); the highest rates were among black non-Hispanic men. Overall, 87.6% (902/1030) of interviewed men in 2016 disclosed >1 male partner. HIV co-infection rates are high among MSM with P&S syphilis (43.4%; 394/907 in 2016), but appear to be decreasing (from 54.1% in 2012). Maps highlighted SH clinics' contribution to diagnosing P&S syphilis cases among men of color. HIV co-infection rates were lower among men with P&S syphilis diagnosed in SH clinics than among those diagnosed elsewhere (34%, SH clinics versus 49%, other settings, p<0.0001). CONCLUSIONS: Syphilis infections continue to increase among MSM in NYC. Novel interventions responsive to the drivers of the current outbreak are needed. |
Laboratory validation of the sand fly fever virus antigen assay
Reeves WK , Szymczak MS , Burkhalter KL , Miller MM . J Am Mosq Control Assoc 2015 31 (4) 380-3 Sandfly fever group viruses in the genus Phlebovirus (family Bunyaviridae) are widely distributed across the globe and are a cause of disease in military troops and indigenous peoples. We assessed the laboratory sensitivity and specificity of the Sand Fly Fever Virus Antigen Assay, a rapid dipstick assay designed to detect sandfly fever Naples virus (SFNV) and Toscana virus (TOSV) against a panel of phleboviruses. The assay detected SFNV and TOSV, as well as other phleboviruses including Aguacate, Anahanga, Arumowot, Chagres, and Punta Toro viruses. It did not detect sandfly fever Sicilian, Heartland, Rio Grande, or Rift Valley fever viruses. It did not produce false positive results in the presence of uninfected sand flies (Lutzomyia longipalpis) or Cache Valley virus, a distantly related bunyavirus. Results from this laboratory evaluation suggest that this assay may be used as a rapid field-deployable assay to detect sand flies infected with TOSV and SFNV, as well as an assortment of other phleboviruses. |
Urinary phthalate metabolites in relation to maternal serum thyroid and sex hormone levels during pregnancy: a longitudinal analysis
Johns LE , Ferguson KK , Soldin OP , Cantonwine DE , Rivera-Gonzalez LO , Del Toro LV , Calafat AM , Ye X , Alshawabkeh AN , Cordero JF , Meeker JD . Reprod Biol Endocrinol 2015 13 4 BACKGROUND: Increasing scientific evidence suggests that exposure to phthalates during pregnancy may be associated with an elevated risk of adverse reproductive outcomes such as preterm birth. Maternal endocrine disruption across pregnancy may be one pathway mediating some of these relationships. We investigated whether urinary phthalate metabolites were associated with maternal serum thyroid (free thyroxine [FT4], free triiodothyronine [FT3], and thyroid-stimulating hormone [TSH]), and sex (estradiol, progesterone, and sex hormone-binding globulin [SHBG]) hormone levels at multiple time points during pregnancy. METHODS: Preliminary data (n = 106) were obtained from an ongoing prospective birth cohort in Northern Puerto Rico. We collected urine and serum sample at the first and third study visits that occurred at 18 +/- 2 and 26 +/- 2 weeks of gestation, respectively. To explore the longitudinal relationships between urinary phthalate metabolites and serum thyroid and sex hormone concentrations, we used linear mixed models (LMMs) adjusted for prepregnancy body mass index (BMI) and maternal age. An interaction term was added to each LMM to test whether the effect of urinary phthalate metabolites on serum thyroid and sex hormone levels varied by study visit. In cross-sectional analyses, we stratified BMI- and age-adjusted linear regression models by study visit. RESULTS: In adjusted LMMs, we observed significant inverse associations between mono-3-carboxypropyl phthalate (MCPP) and FT3 and between mono-ethyl phthalate (MEP) and progesterone. In cross-sectional analyses by study visit, we detected stronger and statistically significant inverse associations at the third study visit between FT3 and MCPP as well as mono-carboxyisooctyl phthalate (MCOP); also at the third study visit, significant inverse associations were observed between FT4 and metabolites of di-(2-ethylhexyl) phthalate (DEHP). The inverse association between MEP and progesterone was consistent across study visits. CONCLUSIONS: In this group of pregnant women, urinary phthalate metabolites may be associated with altered maternal serum thyroid and sex hormone levels, and the magnitude of these effects may depend on the timing of exposure during gestation. |
Distribution and determinants of urinary biomarkers of exposure to organophosphate insecticides in Puerto Rican pregnant women
Lewis RC , Cantonwine DE , Anzalota Del Toro LV , Calafat AM , Valentin-Blasini L , Davis MD , Montesano MA , Alshawabkeh AN , Cordero JF , Meeker JD . Sci Total Environ 2015 512-513c 337-344 Globally, human exposures to organophosphate (OP) insecticides may pose a significant burden to the health of mothers and their developing fetuses. Unfortunately, relevant data is limited in certain areas of the world concerning sources of exposure to OP insecticides in pregnant populations. To begin to address this gap in information for Puerto Rico, we studied repeated measures of urinary concentrations of 10 OP insecticide metabolites among 54 pregnant women from the northern karst region of the island. We also collected demographic data and self-reported information on the consumption of fruits, vegetables, and legumes in the past 48h before urine collection and home pest-related issues. We calculated the distributions of the urinary biomarkers and compared them to women of reproductive age from the general U.S. population. We also used statistical models accounting for correlated data to assess within-subject temporal variability of the urinary biomarkers and to identify predictors of exposure. We found that for all but two metabolites (para-nitrophenol [PNP], diethylthiophosphate [DETP]), 50th or 95th percentile urinary concentrations (the metric that was used for comparison was based on the biomarker's detection frequency) of the other eight metabolites (3,5,6-trichloro-2-pyridinol [TCPY], 2-isopropyl-4-methyl-6-hydroxy-pyrimidine, malathion dicarboxylic acid, diethylphosphate, diethyldithiophosphate, dimethylphosphate, dimethylthiophosphate [DMTP], dimethyldithiophosphate) were somewhat lower in our cohort compared with similarly aged women from the continental United States. TCPY, PNP, DETP, and DMTP, which were the only urinary metabolites detected in greater than 50% of the samples, had poor reproducibility (intraclass correlation coefficient range: 0.19-0.28) during pregnancy. Positive predictors of OP insecticide exposure included: age; marital or employment status; consumption of cherries, grape juice, peanuts, peanut butter, or raisins; and residential application of pesticides. Further research is needed to understand what aspects of the predictors identified influence OP insecticide exposure during pregnancy. |
Urinary biomarkers of exposure to insecticides, herbicides, and one insect repellent among pregnant women in Puerto Rico
Lewis RC , Cantonwine DE , Anzalota Del Toro LV , Calafat AM , Valentin-Blasini L , Davis MD , Baker SE , Alshawabkeh AN , Cordero JF , Meeker JD . Environ Health 2014 13 97 BACKGROUND: There are potential adverse health risks to the mother and fetus from exposure to pesticides. Thus, studies of exposure to pesticides among pregnant women are of interest as they will assist with understanding the potential burden of exposure globally, identifying sources of exposure, and designing epidemiology studies. METHODS: We measured urinary concentrations of the insect repellent N-N-diethyl-meta-toluamide (DEET) and two of its metabolites [3-diethyl-carbamoyl benzoic acid (DCBA) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB)], four pyrethroid insecticide metabolites [4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA); 3-phenoxybenzoic acid (3-PBA); trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA); and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA)], and two chlorophenoxy herbicides [2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)] in 54 pregnant women from Puerto Rico at three separate time points (20 ± 2 weeks, 24 ± 2 weeks, and 28 ± 2 weeks of gestation). We calculated the distributions of the biomarker concentrations and compared them to those of women of reproductive age from the general U.S. population where available, and estimated the within-subject temporal variability of these repeated measurements. We also collected questionnaire data on demographics, consumption of select fruits, vegetables, and legumes in the past 48-hr, and pest-related issues, and associations between these variables and biomarker concentrations were examined. RESULTS: We found that 95th percentile urinary concentrations of DEET, 3-PBA, trans-DCCA, and 2,4-D were lower than women of reproductive age on the U.S. mainland, whereas 95th percentile urinary concentrations of 4-F-3-PBA, cis-DBCA, and 2,4,5-T were similar. DCBA, the only urinary biomarker detected in >50% of the samples, showed fair to good reproducibility across pregnancy (intraclass correlation coefficient: 0.60). Women were more likely (p <0.05) to have greater urinary concentrations of pesticide biomarkers if they were less educated (DCBA and trans-DCCA), unemployed (DHMB), or married (2,4-D), had consumed collards or spinach in past 48-hr (2,4-D) or had been using insect repellent since becoming pregnant (DCBA), or were involved with residential applications of pesticides (trans-DCCA). CONCLUSIONS: We identified concentrations and predictors of several pesticides among pregnant women in Puerto Rico. Further research is needed to understand what aspects of the predictors identified lead to greater exposure, and whether exposure during pregnancy is associated with adverse health. |
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Wang Z , Zhu B , Zhang M , Parikh H , Jia J , Chung CC , Sampson JN , Hoskins JW , Hutchinson A , Burdette L , Ibrahim A , Hautman C , Raj PS , Abnet CC , Adjei AA , Ahlbom A , Albanes D , Allen NE , Ambrosone CB , Aldrich M , Amiano P , Amos C , Andersson U , Andriole G Jr , Andrulis IL , Arici C , Arslan AA , Austin MA , Baris D , Barkauskas DA , Bassig BA , Beane Freeman LE , Berg CD , Berndt SI , Bertazzi PA , Biritwum RB , Black A , Blot W , Boeing H , Boffetta P , Bolton K , Boutron-Ruault MC , Bracci PM , Brennan P , Brinton LA , Brotzman M , Bueno-de-Mesquita HB , Buring JE , Butler MA , Cai Q , Cancel-Tassin G , Canzian F , Cao G , Caporaso NE , Carrato A , Carreon T , Carta A , Chang GC , Chang IS , Chang-Claude J , Che X , Chen CJ , Chen CY , Chen CH , Chen C , Chen KY , Chen YM , Chokkalingam AP , Chu LW , Clavel-Chapelon F , Colditz GA , Colt JS , Conti D , Cook MB , Cortessis VK , Crawford ED , Cussenot O , Davis FG , De Vivo I , Deng X , Ding T , Dinney CP , Di Stefano AL , Diver WR , Duell EJ , Elena JW , Fan JH , Feigelson HS , Feychting M , Figueroa JD , Flanagan AM , Fraumeni JF Jr , Freedman ND , Fridley BL , Fuchs CS , Gago-Dominguez M , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Garcia-Closas R , Gastier-Foster JM , Gaziano JM , Gerhard DS , Giffen CA , Giles GG , Gillanders EM , Giovannucci EL , Goggins M , Gokgoz N , Goldstein AM , Gonzalez C , Gorlick R , Greene MH , Gross M , Grossman HB , Grubb R 3rd , Gu J , Guan P , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Hartge P , Hattinger C , Hayes RB , He Q , Helman L , Henderson BE , Henriksson R , Hoffman-Bolton J , Hohensee C , Holly EA , Hong YC , Hoover RN , Hosgood HD 3rd , Hsiao CF , Hsing AW , Hsiung CA , Hu N , Hu W , Hu Z , Huang MS , Hunter DJ , Inskip PD , Ito H , Jacobs EJ , Jacobs KB , Jenab M , Ji BT , Johansen C , Johansson M , Johnson A , Kaaks R , Kamat AM , Kamineni A , Karagas M , Khanna C , Khaw KT , Kim C , Kim IS , Kim YH , Kim YC , Kim YT , Kang CH , Jung YJ , Kitahara CM , Klein AP , Klein R , Kogevinas M , Koh WP , Kohno T , Kolonel LN , Kooperberg C , Kratz CP , Krogh V , Kunitoh H , Kurtz RC , Kurucu N , Lan Q , Lathrop M , Lau CC , Lecanda F , Lee KM , Lee MP , Le Marchand L , Lerner SP , Li D , Liao LM , Lim WY , Lin D , Lin J , Lindstrom S , Linet MS , Lissowska J , Liu J , Ljungberg B , Lloreta J , Lu D , Ma J , Malats N , Mannisto S , Marina N , Mastrangelo G , Matsuo K , McGlynn KA , McKean-Cowdin R , McNeill LH , McWilliams RR , Melin BS , Meltzer PS , Mensah JE , Miao X , Michaud DS , Mondul AM , Moore LE , Muir K , Niwa S , Olson SH , Orr N , Panico S , Park JY , Patel AV , Patino-Garcia A , Pavanello S , Peeters PH , Peplonska B , Peters U , Petersen GM , Picci P , Pike MC , Porru S , Prescott J , Pu X , Purdue MP , Qiao YL , Rajaraman P , Riboli E , Risch HA , Rodabough RJ , Rothman N , Ruder AM , Ryu JS , Sanson M , Schned A , Schumacher FR , Schwartz AG , Schwartz KL , Schwenn M , Scotlandi K , Seow A , Serra C , Serra M , Sesso HD , Severi G , Shen H , Shen M , Shete S , Shiraishi K , Shu XO , Siddiq A , Sierrasesumaga L , Sierri S , Sihoe AD , Silverman DT , Simon M , Southey MC , Spector L , Spitz M , Stampfer M , Stattin P , Stern MC , Stevens VL , Stolzenberg-Solomon RZ , Stram DO , Strom SS , Su WC , Sund M , Sung SW , Swerdlow A , Tan W , Tanaka H , Tang W , Tang ZZ , Tardon A , Tay E , Taylor PR , Tettey Y , Thomas DM , Tirabosco R , Tjonneland A , Tobias GS , Toro JR , Travis RC , Trichopoulos D , Troisi R , Truelove A , Tsai YH , Tucker MA , Tumino R , Van Den Berg D , Van Den Eeden SK , Vermeulen R , Vineis P , Visvanathan K , Vogel U , Wang C , Wang C , Wang J , Wang SS , Weiderpass E , Weinstein SJ , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolk A , Wolpin BM , Wong MP , Wrensch M , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xiang YB , Xu J , Yang HP , Yang PC , Yatabe Y , Ye Y , Yeboah ED , Yin Z , Ying C , Yu CJ , Yu K , Yuan JM , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Mirabello L , Savage SA , Kraft P , Chanock SJ , Yeager M , Landi MT , Shi J , Chatterjee N , Amundadottir LT . Hum Mol Genet 2014 23 (24) 6616-33 ![]() Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. |
Urinary phthalate metabolite associations with biomarkers of inflammation and oxidative stress across pregnancy in Puerto Rico
Ferguson KK , Cantonwine DE , Rivera-Gonzalez LO , Loch-Caruso R , Mukherjee B , Anzalota Del Toro LV , Jimenez-Velez B , Calafat AM , Ye X , Alshawabkeh AN , Cordero JF , Meeker JD . Environ Sci Technol 2014 48 (12) 7018-25 Phthalate exposure during pregnancy has been linked to adverse birth outcomes such as preterm birth, and inflammation and oxidative stress may mediate these relationships. In a prospective cohort study of pregnant women recruited early in gestation in Northern Puerto Rico, we investigated the associations between urinary phthalate metabolites and biomarkers of inflammation, including C-reactive protein, IL-1beta, IL-6, IL-10, and TNF-alpha, and oxidative stress, including 8-hydroxydeoxyguanosine (OHdG) and 8-isoprostane. Inflammation biomarkers were measured in plasma twice during pregnancy (N = 215 measurements, N = 120 subjects), and oxidative stress biomarkers in urine were measured three times (N = 148 measurements, N = 54 subjects) per woman. In adjusted linear mixed models, metabolites of di-2-ethylhexyl phthalate (DEHP) were associated with increased IL-6 and IL-10 but relationships were generally not statistically significant. All phthalates were associated with increases in oxidative stress markers. Relationships with OHdG were significant for DEHP metabolites as well as mono-n-butyl phthalate (MBP) and monoiso-butyl phthalate (MiBP). For 8-isoprostane, associations with nearly all phthalates were statistically significant and the largest effect estimates were observed for MBP and MiBP (49-50% increase in 8-isoprostane with an interquartile range increase in metabolite concentration). These relationships suggest a possible mechanism for phthalate action that may be relevant to a number of adverse health outcomes. |
Urinary phthalate metabolite concentrations among pregnant women in northern Puerto Rico: distribution, temporal variability, and predictors
Cantonwine DE , Cordero JF , Rivera-Gonzalez LO , Anzalota Del Toro LV , Ferguson KK , Mukherjee B , Calafat AM , Crespo N , Jiménez-Vélez B , Padilla IY , Alshawabkeh AN , Meeker JD . Environ Int 2013 62C 1-11 BACKGROUND: Phthalate contamination exists in the North Coast karst aquifer system in Puerto Rico. In light of potential health impacts associated with phthalate exposure, targeted action for elimination of exposure sources may be warranted, especially for sensitive populations such as pregnant women. However, information on exposure to phthalates from a variety of sources in Puerto Rico is lacking. The objective of this study was to determine concentrations and predictors of urinary phthalate biomarkers measured at multiple times during pregnancy among women living in the Northern karst area of Puerto Rico. METHODS: We recruited 139 pregnant women in Northern Puerto Rico and collected urine samples and questionnaire data at three separate visits (18+/-2weeks, 22+/-2weeks, and 26+/-2weeks of gestation). Urine samples were analyzed for eleven phthalate metabolites: mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-benzyl phthalate, mono-isobutyl phthalate, mono-3-carboxypropyl phthalate (MCPP), mono carboxyisononyl phthalate (MCNP), and mono carboxyisooctyl phthalate (MCOP). RESULTS: Detectable concentrations of phthalate metabolites among pregnant women living in Puerto Rico was prevalent, and metabolite concentrations tended to be higher than or similar to those measured in women of reproductive age from the general US population. Intraclass correlation coefficients ranged from very weak (MCNP; 0.05) to moderate (MEP; 0.44) reproducibility among all phthalate metabolites. We observed significant or suggestive positive associations between urinary phthalate metabolite concentrations and water usage/storage habits (MEP, MCNP, MCOP), use of personal care products (MEP), and consumption of certain food items (MCPP, MCNP, and MCOP). CONCLUSIONS: To our knowledge this is the first study to report concentrations, temporal variability, and predictors of phthalate biomarkers among pregnant women in Puerto Rico. Preliminary results suggest several potentially important exposure sources to phthalates in this population and future analysis from this ongoing prospective cohort will help to inform targeted approaches to reduce exposure. |
The utility of animal surveillance in the detection of West Nile virus activity in Puerto Rico, 2007
Phoutrides E , Jusino-Mendez T , Perez-Medina T , Seda-Lozada R , Garcia-Negron M , Davila-Toro F , Hunsperger E . Vector Borne Zoonotic Dis 2010 11 (4) 447-50 After the isolation of West Nile virus (WNV) from humans, mosquitoes, and chickens in 2007, an analysis of animal surveillance involving multiple species (horses, monkeys, sheep, dogs, and birds) used to track WNV transmission from 2006 to 2008 was performed. During this period 13.4% of all the animal samples collected were seropositive by blocking ELISA for WNV. The most complete island-wide sampling was obtained from horses of which 22% were serologically positive and 96% were confirmed as WNV infections by plaque-reduction neutralization test. Our conclusion from this 3-year study is that animal surveillance is an early indicator of WNV activity before the identification of human cases. Additionally, the results indicated that horses have a greater geographical range and should be continued to be used as sentinels for passive surveillance in the tropics. |
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