Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
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Query Trace: Hunsperger EA [original query] |
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Characterizing the countrywide epidemic spread of influenza A(H1N1)pdm09 virus in Kenya between 2009 and 2018 (preprint)
Owuor DC , de Laurent ZR , Kikwai GK , Mayieka LM , Ochieng M , Müller NF , Otieno NA , Emukule GO , Hunsperger EA , Garten R , Barnes JR , Chaves SS , Nokes DJ , Agoti CN . medRxiv 2021 2021.03.30.21254587 Background The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data is lacking.Methods We isolated, sequenced, and analyzed 383 influenza A(H1N1)pdm09 viral genomes isolated from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods.Results The transmission dynamics of influenza A(H1N1)pdm09 virus in Kenya was characterized by: (i) multiple virus introductions into Kenya over the study period, although these were remarkably few, with only a few of those introductions instigating seasonal epidemics that then established local transmission clusters; (ii) persistence of transmission clusters over several epidemic seasons across the country; (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres; (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-11 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-17; and (v) virus migration from multiple geographical regions to multiple geographical destinations in Kenya.Conclusion Considerable influenza virus diversity circulates within Africa, as demonstrated in this report, including virus lineages that are unique to the region, which may be capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding: The authors D.C.O. and C.N.A. were supported by the Initiative to Develop African Research Leaders (IDeAL) through the DELTAS Africa Initiative [DEL-15-003]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. The study was also part funded by a Wellcome Trust grant [1029745] and the USA CDC grant [GH002133]. N.F.M. is supported by the Swiss National Science Foundation (PZEZP3_191891). This paper is published with the permission of the Director of KEMRI.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Kenya Medical Research Institute (KEMRI) and KEMRI-Wellcome Trust Research Programme Scientific and Ethics Review Unit (SERU), which is mandated to provide ethical approval for research work conducted in Kenya, provided ethical approval for the studies which collected and archived the samples used in these studies. These were approved under the following Scientific Steering Committee (SSC) approvals: 1. SSC No. 1899, SSC No. 2558 and SSC No. 2692; 2. KEMRI-Wellcome Trust Research Programme SSC No. 1055 and SSC No. 1433.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as Clini alTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll generated sequence data were deposited in the Global Initiative on Sharing All Influenza Data (GISAID). https://github.com/DCollinsOwuor/H1N1pdm09_Kenya_Phylodynamics/tree/main/Data/. |
Outbreak of Middle East Respiratory Syndrome Coronavirus in Camels and Probable Spillover Infection to Humans in Kenya.
Ngere I , Hunsperger EA , Tong S , Oyugi J , Jaoko W , Harcourt JL , Thornburg NJ , Oyas H , Muturi M , Osoro EM , Gachohi J , Ombok C , Dawa J , Tao Y , Zhang J , Mwasi L , Ochieng C , Mwatondo A , Bodha B , Langat D , Herman-Roloff A , Njenga MK , Widdowson MA , Munyua PM . Viruses 2022 14 (8) The majority of Kenya's > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0-24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April-September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya. |
Characterizing the Countrywide Epidemic Spread of Influenza A(H1N1)pdm09 Virus in Kenya between 2009 and 2018.
Owuor DC , de Laurent ZR , Kikwai GK , Mayieka LM , Ochieng M , Müller NF , Otieno NA , Emukule GO , Hunsperger EA , Garten R , Barnes JR , Chaves SS , Nokes DJ , Agoti CN . Viruses 2021 13 (10) The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (R(e)) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions. |
Distinguishing patients with laboratory-confirmed chikungunya from dengue and other acute febrile illnesses, Puerto Rico, 2012-2015
Alvarado LI , Lorenzi OD , Torres-Velasquez BC , Sharp TM , Vargas L , Munoz-Jordan JL , Hunsperger EA , Perez-Padilla J , Rivera A , Gonzalez-Zeno GE , Galloway RL , Glass Elrod M , Mathis DL , Oberste MS , Nix WA , Henderson E , McQuiston J , Singleton J , Kato C , Garcia-Gubern C , Santiago-Rivera W , Muns-Sosa R , Ortiz-Rivera JD , Jimenez G , Rivera-Amill V , Andujar-Perez DA , Horiuchi K , Tomashek KM . PLoS Negl Trop Dis 2019 13 (7) e0007562 Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever </=7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI. |
Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015
Tomashek KM , Lorenzi OD , Andujar-Perez DA , Torres-Velasquez BC , Hunsperger EA , Munoz-Jordan JL , Perez-Padilla J , Rivera A , Gonzalez-Zeno GE , Sharp TM , Galloway RL , Glass Elrod M , Mathis DL , Oberste MS , Nix WA , Henderson E , McQuiston J , Singleton J , Kato C , Garcia Gubern C , Santiago-Rivera W , Cruz-Correa J , Muns-Sosa R , Ortiz-Rivera JD , Jimenez G , Galarza IE , Horiuchi K , Margolis HS , Alvarado LI . PLoS Negl Trop Dis 2017 11 (9) e0005859 Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management. |
Rapid and accurate interpretation of dengue diagnostics in the context of dengue vaccination implementation: Viewpoints and guidelines issued from an experts group consultation
Hunsperger EA , Duarte Dos Santos CN , Vu HTQ , Yoksan S , Deubel V . PLoS Negl Trop Dis 2017 11 (9) e0005719 There are 4 serologically distinct dengue viruses (DENVs), which contemporarily cocirculate in a majority of countries of the tropical and subtropical belt in Latin America, Asia-Pacific, and Africa [1]. DENVs are members of the Flavivirus genus, related to other medically important mosquito-borne viruses such as yellow fever virus (YFV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). A chimeric YF-DEN tetravalent dengue vaccine CYD-TDV (Dengvaxia) has now been licensed in 13 countries [2]. A phase IIb trial in Thailand and 2 phase III large-scale efficacy trials in 10 countries in Asia and Latin America have been conducted [2]. The vaccine clinical monitoring and careful diagnosis of the vaccinated and unvaccinated populations enrolled in these studies have provided valuable information that is useful for the later stage of vaccination implementation and its monitoring [2]. A recent study of the validity of the serological diagnosis of dengue immunoglobulin G (IgG) and immunoglobulin M (IgM) by ELISA according to WHO recommendations [3] in acute febrile and in convalescent individuals vaccinated and unvaccinated (Placebo), and virologically confirmed or not, showed a high sensitivity (97.1%) but a low specificity (85.1%) in the IgM ELISA due to the presence of residual IgM from previous vaccination or subclinical undetected dengue, which may introduce a diagnostic bias [4]. The proportion of false positives IgM in the CYD-TDV vaccinated group (17.4%) was higher than in the control group (10.1%), particularly within the 2 months following vaccination. Therefore, it was necessary to review and redefine a reliable diagnostic testing algorithm in light of false dengue positives, which would be used by healthcare professionals to confirm suspected dengue cases in vaccinees and to evaluate the effectiveness of the CYD-TDV vaccine in the vaccinated populations. Here, a group of experts in the diagnosis and monitoring of DENV and other flaviviruses has considered key questions regarding sensitive and specific dengue diagnostics and their application for dengue surveillance in countries where the CYD-TDV vaccine has been implemented. |
Enhanced surveillance for fatal dengue-like acute febrile illness in Puerto Rico, 2010-2012
Tomashek KM , Rivera A , Torres-Velasquez B , Hunsperger EA , Munoz-Jordan JL , Sharp TM , Rivera I , Sanabria D , Blau DM , Galloway R , Torres J , Rodriguez R , Serrano J , Chavez C , Davila F , Perez-Padilla J , Ellis EM , Caballero G , Wright L , Zaki SR , Deseda C , Rodriguez E , Margolis HS . PLoS Negl Trop Dis 2016 10 (10) e0005025 BACKGROUND: Dengue is a leading cause of morbidity throughout the tropics; however, accurate population-based estimates of mortality rates are not available. METHODS/PRINCIPAL FINDINGS: We established the Enhanced Fatal Acute Febrile Illness Surveillance System (EFASS) to estimate dengue mortality rates in Puerto Rico. Healthcare professionals submitted serum and tissue specimens from patients who died from a dengue-like acute febrile illness, and death certificates were reviewed to identify additional cases. Specimens were tested for markers of dengue virus (DENV) infection by molecular, immunologic, and immunohistochemical methods, and were also tested for West Nile virus, Leptospira spp., and other pathogens based on histopathologic findings. Medical records were reviewed and clinical data abstracted. A total of 311 deaths were identified, of which 58 (19%) were DENV laboratory-positive. Dengue mortality rates were 1.05 per 100,000 population in 2010, 0.16 in 2011 and 0.36 in 2012. Dengue mortality was highest among adults 19-64 years and seniors ≥65 years (1.17 and 1.66 deaths per 100,000, respectively). Other pathogens identified included 34 Leptospira spp. cases and one case of Burkholderia pseudomallei and Neisseria meningitidis. CONCLUSIONS/SIGNIFICANCE: EFASS showed that dengue mortality rates among adults were higher than reported for influenza, and identified a leptospirosis outbreak and index cases of melioidosis and meningitis. |
Performance of dengue diagnostic tests in a single-specimen diagnostic algorithm
Hunsperger EA , Munoz-Jordan J , Beltran M , Colon C , Carrion J , Vazquez J , Acosta LN , Medina-Izquierdo JF , Horiuchi K , Biggerstaff BJ , Margolis HS . J Infect Dis 2016 214 (6) 836-44 BACKGROUND: Anti-dengue virus (DENV) immunoglobulin M (IgM) seroconversion has been the reference standard for dengue diagnosis. However, paired specimens are rarely obtained, and the interval for this testing negates its usefulness in guiding clinical case management. The presence of DENV viremia and appearance of IgM during the febrile phase of dengue provides the framework for dengue laboratory diagnosis by using a single serum specimen. METHODS: Archived paired serum specimens (n = 1234) from patients with laboratory-confirmed dengue from 2005 through 2011 were used to determine the diagnostic performance of real-time reverse transcription polymerase chain reaction (RT-PCR), for detection of DENV serotypes 1-4, and enzyme-linked immunosorbent assays (ELISAs), for detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM. RESULTS: During 1-3 days after illness onset, real-time RT-PCR and NS1 antigen testing detected 82%-69% and 90%-84% of cases, respectively, as viremia levels declined, while anti-DENV IgM ELISA detected 5%-41% of cases as antibody appeared. Over the 10-day period of the febrile phase of dengue, the cumulative effect of using these 3 types of tests in a diagnostic algorithm confirmed ≥90% of dengue cases. CONCLUSIONS: The use of molecular or NS1 antigen tests to detect DENV and one to detect anti-DENV IgM in a single serum specimen collected during the first 10 days of illness accurately identified ≥90% of dengue primary and secondary cases. |
Non-human primate antibody response to mosquito salivary proteins: Implications for dengue virus transmission in Puerto Rico
Hemme RR , Poole-Smith BK , Hunsperger EA , Felix GE , Horiuchi K , Biggerstaff BJ , Lopez-Ortiz R , Barrera R . Acta Trop 2016 164 369-374 An important step to incriminate a mosquito as a vector of a disease pathogen is finding evidence of direct contact between the mosquito and humans. Typically, this is accomplished through landing/biting catches, or host blood meal analysis in engorged mosquitoes via immunologic assays. An alternate approach is to identify the presence of specific mosquito anti-saliva protein antibodies in the blood of exposed hosts. Following the discovery of dengue infected, free roaming non-human primates in Puerto Rico, we investigated which mosquito species had bitten these primates using a serologic assay. Serum samples from 20 patas monkeys (Erythrocebus patas) and two rhesus macaques (Macaca mulatta) were used to evaluate mosquito bite exposure to Aedes aegypti, Aedes mediovittatus, Aedes taeniorhynchus, and Culex quinquefasciatus mosquitoes. Of 22 non-human primates examined 20 (90%), 17 (77%), 13 (59%), and 7 (31%) were positive for exposure to Ae. mediovittatus, Cx. quinquefasciatus, Ae. taeniorhynchus, and Ae. aegypti, respectively. Our findings indicated that free-roaming primates in Puerto Rico were exposed to the bites of one proven dengue vector, Ae. aegypti and one potential dengue vector, Ae. mediovittatus. |
Use of a Rapid Test for Diagnosis of Dengue during Suspected Dengue Outbreaks in Resource-Limited Regions
Hunsperger EA , Sharp TM , Lalita P , Tikomaidraubuta K , Cardoso YR , Naivalu T , Khan AS , Marfel M , Hancock WT , Tomashek KM , Margolis HS . J Clin Microbiol 2016 Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response leading to initiation of appropriate clinical care. Because the clinical presentation of dengue is non-specific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real time RT-PCR and anti-DENV IgM ELISA were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3-91.7% and 85.3-98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7-92.9% and 22.2-89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. Use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable. |
Binational dengue outbreak along the United States-Mexico border - Yuma County, Arizona, and Sonora, Mexico, 2014
Jones JM , Lopez B , Adams L , Galvez FJ , Nunez AS , Santillan NA , Plante L , Hemme RR , Casal M , Hunsperger EA , Munoz-Jordan J , Acevedo V , Ernst K , Hayden M , Waterman S , Gomez D , Sharp TM , Komatsu KK . MMWR Morb Mortal Wkly Rep 2016 65 (19) 495-499 Dengue is an acute febrile illness caused by any of four dengue virus types (DENV-1-4). DENVs are transmitted by mosquitos of the genus Aedes (1) and are endemic throughout the tropics (2). In 2010, an estimated 390 million DENV infections occurred worldwide (2). During 2007-2013, a total of three to 10 dengue cases were reported annually in Arizona and all were travel-associated. During September-December 2014, coincident with a dengue outbreak in Sonora, Mexico, 93 travel-associated dengue cases were reported in Arizona residents; 70 (75%) cases were among residents of Yuma County, which borders San Luis Rio Colorado, Sonora, Mexico. San Luis Rio Colorado reported its first case of locally acquired dengue in September 2014. To investigate the temporal relationship of the dengue outbreaks in Yuma County and San Luis Rio Colorado and compare patient characteristics and signs and symptoms, passive surveillance data from both locations were analyzed. In addition, household-based cluster investigations were conducted near the residences of reported dengue cases in Yuma County to identify unreported cases and assess risk for local transmission. Surveillance data identified 52 locally acquired cases (21% hospitalized) in San Luis Rio Colorado and 70 travel-associated cases (66% hospitalized) in Yuma County with illness onset during September-December 2014. Among 194 persons who participated in the cluster investigations in Yuma County, 152 (78%) traveled to Mexico at least monthly during the preceding 3 months. Four (2%) of 161 Yuma County residents who provided serum samples for diagnostic testing during cluster investigations had detectable DENV immunoglobulin M (IgM); one reported a recent febrile illness, and all four had traveled to Mexico during the preceding 3 months. Entomologic assessments among 105 households revealed 24 water containers per 100 houses colonized by Ae. aegypti. Frequent travel to Mexico and Ae. aegypti colonization indicate risk for local transmission of DENV in Yuma County. Public health officials in Sonora and Arizona should continue to collaborate on dengue surveillance and educate the public regarding mosquito abatement and avoidance practices. Clinicians evaluating patients from the U.S.-Mexico border region should consider dengue in patients with acute febrile illness and report suspected cases to public health authorities. |
Serological evidence of infection with endemic human pathogens among free-ranging old world monkeys in Puerto Rico
Hemme RR , Lopez-Ortiz R , Garcia BR , Sharp TM , Galloway RL , Elrod MG , Hunsperger EA . Am J Trop Med Hyg 2016 94 (5) 1095-9 Serum specimens from free-ranging but nonnative patas monkeys (Erythrocebus patas) and rhesus macaques (Macaca mulatta) in southwestern Puerto Rico (PR) were tested for antibodies to infection with dengue viruses (DENVs), West Nile virus (WNV), Leptospira species, and Burkholderia pseudomallei by microneutralization, plaque reduction neutralization, microscopic agglutination, and indirect hemagglutination, respectively. Of 23 animals (21 E. patas and two M. mulatta) tested, all had evidence of prior DENV infection, and of 17 animals tested for WNV, nine (53%) had evidence of prior infection. Of 24 (22 E. patas, two M. mulatta) tested for Leptospira spp., 10 (42%) had evidence of prior exposure, and one patas monkey had antibodies against B. pseudomallei. The acquisition of pathogens endemic among humans in PR by resident nonhuman primates merits further study to define modes of acquisition. |
Comparison of vector competence of Aedes mediovittatus and Aedes aegypti for dengue virus: implications for dengue control in the Caribbean
Poole-Smith BK , Hemme RR , Delorey M , Felix G , Gonzalez AL , Amador M , Hunsperger EA , Barrera R . PLoS Negl Trop Dis 2015 9 (2) e0003462 BACKGROUND: Aedes mediovittatus mosquitoes are found throughout the Greater Antilles in the Caribbean and often share the same larval habitats with Ae. Aegypti, the primary vector for dengue virus (DENV). Implementation of vector control measures to control dengue that specifically target Ae. Aegypti may not control DENV transmission in Puerto Rico (PR). Even if Ae. Aegypti is eliminated or DENV refractory mosquitoes are released, DENV transmission may not cease when other competent mosquito species like Ae. Mediovittatus are present. To compare vector competence of Ae. Mediovittatus and Ae. Aegypti mosquitoes, we studied relative infection and transmission rates for all four DENV serotypes. METHODS: To compare the vector competence of Ae. Mediovittatus and Ae. Aegypti, mosquitoes were exposed to DENV 1-4 per os at viral titers of 5-6 logs plaque-forming unit (pfu) equivalents. At 14 days post infectious bloodmeal, viral RNA was extracted and tested by qRT-PCR to determine infection and transmission rates. Infection and transmission rates were analyzed with a generalized linear model assuming a binomial distribution. RESULTS: Ae. Aegypti had significantly higher DENV-4 infection and transmission rates than Ae. mediovittatus. CONCLUSIONS: This study determined that Ae. Mediovittatus is a competent DENV vector. Therefore dengue prevention programs in PR and the Caribbean should consider both Ae. Mediovittatus and Ae. Aegypti mosquitoes in their vector control programs. |
Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody
Hunsperger EA , Yoksan S , Buchy P , Nguyen VC , Sekaran SD , Enria DA , Vazquez S , Cartozian E , Pelegrino JL , Artsob H , Guzman MG , Olliaro P , Zwang J , Guillerm M , Kliks S , Halstead S , Peeling RW , Margolis HS . PLoS Negl Trop Dis 2014 8 (10) e3171 Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60-75% and specificity 71-80%; NS1 RDT sensitivity was 38-71% and specificity 76-80%; the IgM anti-DENV RDTs sensitivity was 30-96%, with a specificity of 86-92%, and IgM anti-DENV ELISA sensitivity was 96-98% and specificity 78-91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88-94%. |
Discovery and characterization of potential prognostic biomarkers for dengue hemorrhagic fever
Poole-Smith BK , Gilbert A , Gonzalez AL , Beltran M , Tomashek KM , Ward BJ , Hunsperger EA , Ndao M . Am J Trop Med Hyg 2014 91 (6) 1218-26 Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2-5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue. |
Optimization of the cut-off value for a commercial anti-dengue virus IgG immunoassay
Marrero-Santos KM , Beltran M , Carrion-Lebron J , Sanchez-Vegas C , Hamer DH , Barnett ED , Santiago LM , Hunsperger EA . Clin Vaccine Immunol 2013 20 (3) 358-62 A commercial anti-dengue virus (DENV) indirect IgG enzyme-linked immunosorbent assay (ELISA) for serological diagnosis was evaluated for its utility in determining previous DENV exposure in US travelers. The Boston Area Travel Medicine Network clinics used Focus Diagnostics anti-DENV IgG ELISA to measure anti-DENV IgG antibodies in 591 pre-travel specimens from US residents who had traveled to dengue endemic countries. When using the manufacturer's index cut-off value for this ELISA, false-positive results were observed that overestimated the perceived past DENV exposure in US travelers. Validation of 121 of these anti-DENV IgG results by plaque reduction neutralization test (PRNT) was used for receiver operator characteristics (ROC) curve optimization of the index cut-off value from 1 to 3.0, improving the specificity of the anti-DENV IgG ELISA from 24% to 95.7%. Additionally, previous vaccination with yellow fever virus contributed to 52.8% of the false positive rate in the anti-DENV IgG ELISA results. Optimization of the cut-off value of the anti-DENV IgG ELISA provided better interpretation and confidence in the results and eliminated the need for confirmation by PRNT. The travel history of US travelers was also useful for categorizing these travelers in groups for analysis of previous DENV exposure. |
Dengue outbreak in Key West, Florida, USA, 2009
Radke EG , Gregory CJ , Kintziger KW , Sauber-Schatz EK , Hunsperger EA , Gallagher GR , Barber JM , Biggerstaff BJ , Stanek DR , Tomashek KM , Blackmore CG . Emerg Infect Dis 2012 18 (1) 135-7 After 3 dengue cases were acquired in Key West, Florida, we conducted a serosurvey to determine the scope of the outbreak. Thirteen residents showed recent infection (infection rate 5%; 90% CI 2%-8%), demonstrating the reemergence of dengue in Florida. Increased awareness of dengue among health care providers is needed. |
Dengue virus seroprevalence among febrile patients in Bamako, Mali: results of a 2006 surveillance study
Phoutrides EK , Coulibaly MB , George CM , Sacko A , Traore S , Bessoff K , Wiley MR , Kolivras KN , Adelman Z , Traore M , Hunsperger EA . Vector Borne Zoonotic Dis 2011 11 (11) 1479-85 BACKGROUND: Dengue viruses (DENV) are endemic in over 100 countries worldwide, and annually 50 to 100 million people are infected by one of the four DENV serotypes, whereas over 2.5 billion people are at risk for infection. West African countries lack the surveillance to determine the true incidence of dengue; hence, this disease is likely significantly underestimated. In Mali, approximately 14 million people are potentially at risk of acquiring a dengue infection. METHODS AND FINDINGS: A serosurvey for DENV was conducted on 95 human serum samples obtained from the Institute National de Recherche en Sante Publique in 2006. DENV-specific IgM and IgG enzyme-linked immunosorbent assays were performed on all samples, and a subset was tested using the plaque-reduction neutralization test against the DENV and yellow fever virus (YFV). Samples collected during the acute infection (0-5 days postonset of symptoms) were tested for dengue NS1 antigen and reverse-transcriptase polymerase chain reaction for Flaviviruses, Alphaviruses, and Bunyaviruses RNA. A total of 87 (93%) of samples were positive for anti-DENV IgG antibodies. Of a subset of 13 IgG positive samples, 2 samples neutralized monotypically against DENV-1 and -2, whereas 3 others neutralized broadly against YFV and multiple DENV. Although no polymerase chain reaction positives were found, DENV NS1 was detected in 1 of the 20 acute samples tested. CONCLUSIONS: Of the 93 human serum samples tested, the dengue prevalence based on dengue IgG enzyme-linked immunosorbent assay results was 93%. Three DENV specific positive samples and two YFV positives were identified by plaque-reduction neutralization test. Finally, one sample tested positive for dengue NS1, thus suggestive of an acute infection within 14 days of obtaining the sample from the patient. Based on these serological data from this study, YFV and DENV appear to be co-circulating in Mali. |
Mosquito vectors of West Nile virus during an epizootic outbreak in Puerto Rico
Barrera R , MacKay A , Amador M , Vasquez J , Smith J , Diaz A , Acevedo V , Caban B , Hunsperger EA , Munoz-Jordan JL . J Med Entomol 2010 47 (6) 1185-1195 The purpose of this investigation was to identify the mosquito (Diptera: Culicidae) vectors of West Nile virus (WNV; family Flaviviridae, genus Flavivirus) during an epizootic WNV outbreak in eastern Puerto Rico in 2007. In June 2006, 12 sentinel chicken pens with five chickens per pen were deployed in six types of habitats: herbaceous wetlands, mangrove forests, deciduous forests, evergreen forests, rural areas, and urban areas. Once WNV seroconversion in chickens was detected in June 2007, we began trapping mosquitoes using Centers for Disease Control and Prevention (CDC) miniature (light/CO2-baited) traps, CMT-20 collapsible mosquito (CO2- and ISCA SkinLure-baited) traps, and CDC gravid (hay infusion-baited) traps. We placed the CDC miniature traps both 2-4 m and >30 m from the chicken pens, the collapsible traps 2-4 m from the pens, and the gravid traps in backyards of houses with sentinel chicken pens and in a wetland adjacent to an urban area. We found numerous blood-engorged mosquitoes in the traps nearest to the sentinel chickens and reasoned that any such mosquitoes with a disseminated WNV infection likely served as vectors for the transmission of WNV to the sentinels. We used reverse transcriptase-polymerase chain reaction and isolation (C636) on pools of heads, thoraxes/abdomens, and legs of collected blood-engorged mosquitoes to determine whether the mosquitoes carried WNV. We detected WNV-disseminated infections in and obtained WNV isolates from Culex nigripalpus Theo (minimum infection rate [MIR] 1.1-9.7/1,000), Culex bahamensis Dyar and Knab (MIR 1.8-6.0/1,000), and Aedes taeniorhynchus (Wied.) (MIR 0.34-0.36/1,000). WNV was also identified in and isolated from the pool of thoraxes and abdomens of Culex quinquefasciatus Say (4.17/1,000) and identified in one pool of thoraxes and abdomens of Culex habilitator Dyar and Knab (13.39/1,000). Accumulated evidence since 2002 suggests that WNV has not become endemic in Puerto Rico. |
West Nile virus from blood donors, vertebrates, and mosquitoes, Puerto Rico, 2007
Hunsperger EA , McElroy KL , Bessoff K , Colon C , Barrera R , Munoz-Jordan JL . Emerg Infect Dis 2009 15 (8) 1298-300 West Nile virus (WNV) was isolated from a human blood donor, a dead falcon, and mosquitoes in Puerto Rico in 2007. Phylogenetic analysis of the 4 isolates suggests a recent introduction of lineage I WNV that is closely related to WNV currently circulating in North America. |
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