Last data update: Jun 24, 2024. (Total: 47078 publications since 2009)
Records 1-27 (of 27 Records) |
Query Trace: Margolis HS [original query] |
---|
No evidence of acute dengue virus infections at a rural site in western Kenya, 2011 and 2013
Matheson AI , Mogeni OD , Lacsina JR , Ochieng M , Audi A , Bigogo G , Neatherlin J , Margolis HS , Fields B , Ahenda P , Walson JL , Montgomery JM . Am J Trop Med Hyg 2020 103 (5) 2054-2058 The incidence and spread of dengue virus (DENV) have increased rapidly in recent decades. Dengue is underreported in Africa, but recent outbreaks and seroprevalence data suggest that DENV is widespread there. A lack of ongoing surveillance limits knowledge about its spatial reach and hinders disease control planning. We sought to add data on dengue distribution in Kenya through diagnostic testing of serum specimens from persons with an acute febrile illness (AFI) attending an outpatient clinic in rural western Kenya (Asembo) during rainy seasons. Patients with symptoms not likely to be misclassified as dengue (e.g., diarrhea and anemia), those with a positive diagnostic laboratory results which explained their febrile illness, or those with serum collected more than 5 days after fever onset were excluded. However, febrile patients with a positive malaria smear were included in the study. We used reverse transcription polymerase chain reaction (RT-PCR) to test for DENV and IgM anti-DENV to test for recent infection. Of the 615 serum specimens available for testing, none were dengue positive by either RT-PCR or IgM anti-DENV testing. Dengue did not appear to be a cause of febrile illness in this area of western Kenya, although our relatively small sample size may not have identified DENV infections occurring at low incidence. A more widespread AFI surveillance system that includes dengue diagnostic testing by RT-PCR and antibody-based methods is required to more definitively gauge the size and geographic distribution of DENV infection in western Kenya. |
An open challenge to advance probabilistic forecasting for dengue epidemics.
Johansson MA , Apfeldorf KM , Dobson S , Devita J , Buczak AL , Baugher B , Moniz LJ , Bagley T , Babin SM , Guven E , Yamana TK , Shaman J , Moschou T , Lothian N , Lane A , Osborne G , Jiang G , Brooks LC , Farrow DC , Hyun S , Tibshirani RJ , Rosenfeld R , Lessler J , Reich NG , Cummings DAT , Lauer SA , Moore SM , Clapham HE , Lowe R , Bailey TC , Garcia-Diez M , Carvalho MS , Rodo X , Sardar T , Paul R , Ray EL , Sakrejda K , Brown AC , Meng X , Osoba O , Vardavas R , Manheim D , Moore M , Rao DM , Porco TC , Ackley S , Liu F , Worden L , Convertino M , Liu Y , Reddy A , Ortiz E , Rivero J , Brito H , Juarrero A , Johnson LR , Gramacy RB , Cohen JM , Mordecai EA , Murdock CC , Rohr JR , Ryan SJ , Stewart-Ibarra AM , Weikel DP , Jutla A , Khan R , Poultney M , Colwell RR , Rivera-Garcia B , Barker CM , Bell JE , Biggerstaff M , Swerdlow D , Mier YTeran-Romero L , Forshey BM , Trtanj J , Asher J , Clay M , Margolis HS , Hebbeler AM , George D , Chretien JP . Proc Natl Acad Sci U S A 2019 116 (48) 24268-24274 ![]() ![]() A wide range of research has promised new tools for forecasting infectious disease dynamics, but little of that research is currently being applied in practice, because tools do not address key public health needs, do not produce probabilistic forecasts, have not been evaluated on external data, or do not provide sufficient forecast skill to be useful. We developed an open collaborative forecasting challenge to assess probabilistic forecasts for seasonal epidemics of dengue, a major global public health problem. Sixteen teams used a variety of methods and data to generate forecasts for 3 epidemiological targets (peak incidence, the week of the peak, and total incidence) over 8 dengue seasons in Iquitos, Peru and San Juan, Puerto Rico. Forecast skill was highly variable across teams and targets. While numerous forecasts showed high skill for midseason situational awareness, early season skill was low, and skill was generally lowest for high incidence seasons, those for which forecasts would be most valuable. A comparison of modeling approaches revealed that average forecast skill was lower for models including biologically meaningful data and mechanisms and that both multimodel and multiteam ensemble forecasts consistently outperformed individual model forecasts. Leveraging these insights, data, and the forecasting framework will be critical to improve forecast skill and the application of forecasts in real time for epidemic preparedness and response. Moreover, key components of this project-integration with public health needs, a common forecasting framework, shared and standardized data, and open participation-can help advance infectious disease forecasting beyond dengue. |
Lessons learned from dengue surveillance and research, Puerto Rico, 1899-2013
Sharp TM , Ryff KR , Santiago GA , Margolis HS , Waterman SH . Emerg Infect Dis 2019 25 (8) 1522-1530 Dengue was first reported in Puerto Rico in 1899 and sporadically thereafter. Following outbreaks in 1963 and 1969, the Centers for Disease Control and Prevention has worked closely with the Puerto Rico Department of Health to monitor and reduce the public health burden of dengue. During that time, evolving epidemiologic scenarios have provided opportunities to establish, improve, and expand disease surveillance and interventional research projects. These initiatives have enriched the tools available to the global public health community to understand and combat dengue, including diagnostic tests, methods for disease and vector surveillance, and vector control techniques. Our review serves as a guide to organizations seeking to establish dengue surveillance and research programs by highlighting accomplishments, challenges, and lessons learned during more than a century of dengue surveillance and research conducted in Puerto Rico. |
Autocidal gravid ovitraps protect humans from chikungunya virus infection by reducing Aedes aegypti mosquito populations
Sharp TM , Lorenzi O , Torres-Velasquez B , Acevedo V , Perez-Padilla J , Rivera A , Munoz-Jordan J , Margolis HS , Waterman SH , Biggerstaff BJ , Paz-Bailey G , Barrera R . PLoS Negl Trop Dis 2019 13 (7) e0007538 BACKGROUND: Public health responses to outbreaks of dengue, chikungunya, and Zika virus have been stymied by the inability to control the primary vector, Aedes aegypti mosquitos. Consequently, the need for novel approaches to Aedes vector control is urgent. Placement of three autocidal gravid ovitraps (AGO traps) in ~85% of homes in a community was previously shown to sustainably reduce the density of female Ae. aegypti by >80%. Following the introduction of chikungunya virus (CHIKV) to Puerto Rico, we conducted a seroprevalence survey to estimate the prevalence of CHIKV infection in communities with and without AGO traps and evaluate their effect on reducing CHIKV transmission. METHODS AND FINDINGS: Multivariate models that calculated adjusted prevalence ratios (aPR) showed that among 175 and 152 residents of communities with and without AGO traps, respectively, an estimated 26.1% and 43.8% had been infected with CHIKV (aPR = 0.50, 95% CI: 0.37-0.91). After stratification by time spent in their community, protection from CHIKV infection was strongest among residents who reported spending many or all weekly daytime hours in their community:10.3% seropositive in communities with AGO traps vs. 48.7% in communities without (PR = 0.21, 95% CI: 0.11-0.41). The age-adjusted rate of fever with arthralgia attributable to CHIKV infection was 58% (95% CI: 46-66%). The monthly number of CHIKV-infected mosquitos and symptomatic residents were diminished in communities with AGO traps compared to those without. CONCLUSIONS: These findings indicate that AGO traps are an effective tool that protects humans from infection with a virus transmitted by Ae. aegypti mosquitos. Future studies should evaluate their protective effectiveness in large, urban communities. |
Estimating dengue under-reporting in Puerto Rico using a multiplier model
Shankar MB , Rodriguez-Acosta RL , Sharp TM , Tomashek KM , Margolis HS , Meltzer MI . PLoS Negl Trop Dis 2018 12 (8) e0006650 Dengue is a mosquito-borne viral illness that causes a variety of health outcomes, from a mild acute febrile illness to potentially fatal severe dengue. Between 2005 and 2010, the annual number of suspected dengue cases reported to the Passive Dengue Surveillance System (PDSS) in Puerto Rico ranged from 2,346 in 2006 to 22,496 in 2010. Like other passive surveillance systems, PDSS is subject to under-reporting. To estimate the degree of under-reporting in Puerto Rico, we built separate inpatient and outpatient probability-based multiplier models, using data from two different surveillance systems-PDSS and the enhanced dengue surveillance system (EDSS). We adjusted reported cases to account for sensitivity of diagnostic tests, specimens with indeterminate results, and differences between PDSS and EDSS in numbers of reported dengue cases. In addition, for outpatients, we adjusted for the fact that less than 100% of medical providers submit diagnostic specimens from suspected cases. We estimated that a multiplication factor of between 5 (for 2010 data) to 9 (for 2006 data) must be used to correct for the under-reporting of the number of laboratory-positive dengue inpatients. Multiplication factors of between 21 (for 2010 data) to 115 (for 2008 data) must be used to correct for the under-reporting of laboratory-positive dengue outpatients. We also estimated that, after correcting for underreporting, the mean annual rate, for 2005-2010, of medically attended dengue in Puerto Rico to be between 2.1 (for dengue inpatients) to 7.8 (for dengue outpatients) per 1,000 population. These estimated rates compare to the reported rates of 0.4 (dengue outpatients) to 0.1 (dengue inpatients) per 1,000 population. The multipliers, while subject to limitations, will help public health officials correct for underreporting of dengue cases, and thus better evaluate the cost-and-benefits of possible interventions. |
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. |
A new look at an old disease: Recent insights into the global epidemiology of dengue
Sharp TM , Tomashek KM , Read JS , Margolis HS , Waterman SH . Curr Epidemiol Rep 2017 4 (1) 11-21 PURPOSE OF REVIEW: By all measures, the morbidity and mortality due to dengue are continuing to worsen worldwide. Although both early and recent studies have demonstrated regional differences in how dengue affects local populations, these findings were to varying extents related to disparate surveillance approaches. RECENT FINDINGS: Recent studies have broadened the recognized spectrum of disease resulting from DENV infection, particularly in adults, and have also demonstrated new mechanisms of DENV spread both within and between populations. New results regarding the frequency and duration of homo- and heterotypic anti-DENV antibodies have provided important insights relevant to vaccine design and implementation. SUMMARY: These observations and findings as well as difficulties in comparing the epidemiology of dengue within and between regions of the world underscore the need for population-based dengue surveillance worldwide. Enhanced surveillance should be implemented to complement passive surveillance in countries in the tropics to establish baseline data in order to define affected populations and evaluate the impact of dengue vaccines and novel vector control interventions. |
Surveillance for chikungunya and dengue during the first year of chikungunya virus circulation in Puerto Rico
Sharp TM , Ryff KR , Alvarado L , Shieh WJ , Zaki SR , Margolis HS , Rivera-Garcia B . J Infect Dis 2016 214 S475-s481 After chikungunya virus (CHIKV) transmission was detected in Puerto Rico in May 2014, multiple surveillance systems were used to describe epidemiologic trends and CHIKV-associated disease. Of 28 327 cases reported via passive surveillance, 6472 were tested for evidence of CHIKV infection, and results for 4399 (68%) were positive. Of 250 participants in household cluster investigations, 70 (28%) had evidence of recent CHIKV infection. Enhanced surveillance for chikungunya at 2 hospitals identified 1566 patients who tested positive for CHIKV, of whom 10.9% were hospitalized. Enhanced surveillance for fatal cases enabled identification of 31 cases in which CHIKV was detected in blood or tissue specimens. All surveillance systems detected a peak incidence of chikungunya in September 2014 and continued circulation in 2015. Concomitant surveillance for dengue demonstrated low incidence, which had decreased before CHIKV was introduced. Multifaceted chikungunya surveillance in Puerto Rico resolved gaps in traditional passive surveillance and enabled a holistic description of the spectrum of disease associated with CHIKV infection. |
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. |
Evidence-based risk assessment and communication: a new global dengue-risk map for travellers and clinicians
Jentes ES , Lash RR , Johansson MA , Sharp TM , Henry R , Brady OJ , Sotir MJ , Hay SI , Margolis HS , Brunette GW . J Travel Med 2016 23 (6) BACKGROUND: International travel can expose travellers to pathogens not commonly found in their countries of residence, like dengue virus. Travellers and the clinicians who advise and treat them have unique needs for understanding the geographic extent of risk for dengue. Specifically, they should assess the need for prevention measures before travel and ensure appropriate treatment of illness post-travel. Previous dengue-risk maps published in the Centers for Disease Control and Prevention's Yellow Book lacked specificity, as there was a binary (risk, no risk) classification. We developed a process to compile evidence, evaluate it and apply more informative risk classifications. METHODS: We collected more than 839 observations from official reports, ProMED reports and published scientific research for the period 2005-2014. We classified each location as frequent/continuous risk if there was evidence of more than 10 dengue cases in at least three of the previous 10 years. For locations that did not fit this criterion, we classified locations as sporadic/uncertain risk if the location had evidence of at least one locally acquired dengue case during the last 10 years. We used expert opinion in limited instances to augment available data in areas where data were sparse. RESULTS: Initial categorizations classified 134 areas as frequent/continuous and 140 areas as sporadic/uncertain. CDC subject matter experts reviewed all initial frequent/continuous and sporadic/uncertain categorizations and the previously uncategorized areas. From this review, most categorizations stayed the same; however, 11 categorizations changed from the initial determinations. CONCLUSIONS: These new risk classifications enable detailed consideration of dengue risk, with clearer meaning and a direct link to the evidence that supports the specific classification. Since many infectious diseases have dynamic risk, strong geographical heterogeneities and varying data quality and availability, using this approach for other diseases can improve the accuracy, clarity and transparency of risk communication. |
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. |
Effect of a dengue clinical case management course on physician practices in Puerto Rico
Han GS , Gregory CJ , Biggerstaff BJ , Horiuchi K , Perez C , Soto-Gomez E , Matos D , Margolis HS , Tomashek KM . Clin Infect Dis 2016 63 (10) 1297-1303 BACKGROUND: Prior to 2010, the clinical management of dengue in Puerto Rico was shown to be inconsistent with World Health Organization guidelines. A four-hour classroom-style course on dengue clinical management was developed in 2009 and mandated in 2010 for Puerto Rico medical licensure. Fifty physicians were trained as 'master trainers' and gave this course to 7,638 physicians. This study evaluated the effect of the course on the clinical management of hospitalized dengue patients. METHODS: Pre- and post-course test responses were analyzed. Changes in physician practices were assessed by reviewing the medical records of 430 adult and 1075 pediatric dengue patients at the 12 hospitals in Puerto Rico that reported the most cases during 2008-2009 (pre-intervention) and 2011 (post-intervention). Mixed-effects logistic regression was used to compare key indicators of dengue management. RESULTS: Physician test scores increased from 48% correct to 72% after the course. Medical record review showed that the percentage of adult patients who did not receive corticosteroids increased from 30% to 68% (OR 5.9, 95% CI 3.7-9.5) and from 91% to 96% in pediatric patients (OR 2.7, 95% CI 1.5-4.9). Usage of isotonic intravenous saline solutions during the critical period increased from 57% to 90% in adult patients (OR 6.2, 95% CI 1.9-20.4) and from 25% to 44% in pediatric patients (OR 3.4, 95% CI 2.2-5.3). CONCLUSIONS: The management of hospitalized dengue patients improved significantly following implementation of a classroom-style physician training course taught by master trainers. An online version of the course was launched in 2014 to expand its reach and sustainability. |
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. |
Epidemiology of Dengue Among Children Aged < 18 Months-Puerto Rico, 1999-2011
Hause AM , Perez-Padilla J , Horiuchi K , Han GS , Hunsperger E , Aiwazian J , Margolis HS , Tomashek KM . Am J Trop Med Hyg 2015 94 (2) 404-408 Dengue, a mosquito-borne viral illness caused by dengue virus types (DENV)-1 to DENV-4, is endemic in Puerto Rico. Severe dengue usually occurs in individuals previously infected with DENV or among infants born to previously infected mothers. To describe clinical features of dengue in infants, we retrospectively characterized dengue patients aged < 18 months reported to the Passive Dengue Surveillance System (PDSS) during 1999-2011. To determine frequency of signs, symptoms, and disease severity, case report forms and medical records were evaluated for patients who tested positive for dengue by reverse transcriptase polymerase chain reaction or anti-DENV immunoglobulin M enzyme-linked immunosorbent assay. Of 4,178 reported patients aged < 18 months, 813 (19%) were laboratory positive. Of these, most had fever (92%), rash (53%), bleeding manifestations (52%), and thrombocytopenia (52%). Medical records were available for 145 (31%) of 472 hospitalized patients, of which 40% had dengue, 23% had dengue with warning signs, and 33% had severe dengue. Mean age of patients with severe dengue was 8 months. Anti-DENV immunoglobulin G (IgG) titers were not statistically different in patients with (50%) and without (59%) severe dengue. In this study, one-third of DENV-infected infants met the severe dengue case definition. The role of maternal anti-DENV IgG in development of severe disease warrants further study in prospective cohorts of mother-infant pairs. |
Underrecognition of dengue during 2013 epidemic in Luanda, Angola
Sharp TM , Moreira R , Soares MJ , Miguel da Costa L , Mann J , DeLorey M , Hunsperger E , Munoz-Jordan JL , Colon C , Margolis HS , de Caravalho A , Tomashek KM . Emerg Infect Dis 2015 21 (8) 1311-6 During the 2013 dengue epidemic in Luanda, Angola, 811 dengue rapid diagnostic test-positive cases were reported to the Ministry of Health. To better understand the magnitude of the epidemic and identify risk factors for dengue virus (DENV) infection, we conducted cluster surveys around households of case-patients and randomly selected households 6 weeks after the peak of the epidemic. Of 173 case cluster participants, 16 (9%) exhibited evidence of recent DENV infection. Of 247 random cluster participants, 25 (10%) had evidence of recent DENV infection. Of 13 recently infected participants who had a recent febrile illness, 7 (54%) had sought medical care, and 1 (14%) was hospitalized with symptoms consistent with severe dengue; however, none received a diagnosis of dengue. Behavior associated with protection from DENV infection included recent use of mosquito repellent or a bed net. These findings suggest that the 2013 dengue epidemic was larger than indicated by passive surveillance data. |
A household serosurvey to estimate the magnitude of a dengue outbreak in Mombasa, Kenya, 2013
Ellis EM , Neatherlin JC , Delorey M , Ochieng M , Mohamed AH , Mogeni DO , Hunsperger E , Patta S , Gikunju S , Waiboic L , Fields B , Ofula V , Konongoi SL , Torres-Velasquez B , Marano N , Sang R , Margolis HS , Montgomery JM , Tomashek KM . PLoS Negl Trop Dis 2015 9 (4) e0003733 Dengue appears to be endemic in Africa with a number of reported outbreaks. In February 2013, several individuals with dengue-like illnesses and negative malaria blood smears were identified in Mombasa, Kenya. Dengue was laboratory confirmed and an investigation was conducted to estimate the magnitude of local transmission including a serologic survey to determine incident dengue virus (DENV) infections. Consenting household members provided serum and were questioned regarding exposures and medical history. RT-PCR was used to identify current DENV infections and IgM anti-DENV ELISA to identify recent infections. Of 1,500 participants from 701 households, 210 (13%) had evidence of current or recent DENV infection. Among those infected, 93 (44%) reported fever in the past month. Most (68, 73%) febrile infected participants were seen by a clinician and all but one of 32 participants who reportedly received a diagnosis were clinically diagnosed as having malaria. Having open windows at night (OR = 2.3; CI: 1.1-4.8), not using daily mosquito repellent (OR = 1.6; CI: 1.0-2.8), and recent travel outside of Kenya (OR = 2.5; CI: 1.1-5.4) were associated with increased risk of DENV infection. This survey provided a robust measure of incident DENV infections in a setting where cases were often unrecognized and misdiagnosed. |
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%. |
Chikungunya cases identified through passive surveillance and household investigations - Puerto Rico, May 5-August 12, 2014
Sharp TM , Roth NM , Torres J , Ryff KR , Perez Rodriguez NM , Mercado C , Pilar Diaz Padro MD , Ramos M , Phillips R , Lozier M , Arriola CS , Johansson M , Hunsperger E , Munoz-Jordan JL , Margolis HS , Garcia BR . MMWR Morb Mortal Wkly Rep 2014 63 (48) 1121-8 Chikungunya and dengue are mosquito-borne, viral, acute febrile illnesses that can be difficult to distinguish clinically. Whereas dengue is endemic in many countries in the Caribbean and the Americas, the first locally acquired chikungunya case in the Western Hemisphere was reported from the Caribbean island of St. Martin in December 2013 and was soon followed by cases in many parts of the region. In January 2014, the Puerto Rico Department of Health (PRDH) and CDC initiated chikungunya surveillance by building on an existing passive dengue surveillance system. To assess the extent of chikungunya in Puerto Rico, the severity of illnesses, and the health care-seeking behaviors of residents, PRDH and CDC analyzed data from passive surveillance and investigations conducted around the households of laboratory-positive chikungunya patients. Passive surveillance indicated that the first locally acquired, laboratory-positive chikungunya case in Puerto Rico was in a patient with illness onset on May 5, 2014. By August 12, a total of 10,201 suspected chikungunya cases (282 per 100,000 residents) had been reported. Specimens from 2,910 suspected cases were tested, and 1,975 (68%) were positive for chikungunya virus (CHIKV) infection. Four deaths were reported. The household investigations found that, of 250 participants, 70 (28%) tested positive for current or recent CHIKV infection, including 59 (84%) who reported illness within the preceding 3 months. Of 25 laboratory-positive participants that sought medical care, five (20%) were diagnosed with chikungunya and two (8%) were reported to PRDH. These investigative efforts indicated that chikungunya cases were underrecognized and underreported, prompting PRDH to conduct information campaigns to increase knowledge of the disease among health care professionals and the public. PRDH and CDC recommended that health care providers manage suspected chikungunya cases as they do dengue because of the similarities in symptoms and increased risk for complications in dengue patients that are not appropriately managed. Residents of and travelers to the tropics can minimize their risk for both chikungunya and dengue by taking standard measures to avoid mosquito bites. |
Dengue virus infections among Haitian and expatriate non-governmental organization workers - Leogane and Port-au-Prince, Haiti, 2012
Salyer SJ , Ellis EM , Salomon C , Bron C , Juin S , Hemme RR , Hunsperger E , Jentes ES , Magloire R , Tomashek KM , Desormeaux AM , Munoz-Jordan JL , Etienne L , Beltran M , Sharp TM , Moffett D , Tappero J , Margolis HS , Katz MA . PLoS Negl Trop Dis 2014 8 (10) e3269 In October 2012, the Haitian Ministry of Health and the US CDC were notified of 25 recent dengue cases, confirmed by rapid diagnostic tests (RDTs), among non-governmental organization (NGO) workers. We conducted a serosurvey among NGO workers in Leogane and Port-au-Prince to determine the extent of and risk factors for dengue virus infection. Of the total 776 staff from targeted NGOs in Leogane and Port-au-Prince, 173 (22%; 52 expatriates and 121 Haitians) participated. Anti-dengue virus (DENV) IgM antibody was detected in 8 (15%) expatriates and 9 (7%) Haitians, and DENV non-structural protein 1 in one expatriate. Anti-DENV IgG antibody was detected in 162 (94%) participants (79% of expatriates; 100% of Haitians), and confirmed by microneutralization testing as DENV-specific in 17/34 (50%) expatriates and 42/42 (100%) Haitians. Of 254 pupae collected from 68 containers, 65% were Aedes aegypti; 27% were Ae. albopictus. Few NGO workers reported undertaking mosquito-avoidance action. Our findings underscore the risk of dengue in expatriate workers in Haiti and Haitians themselves. |
Sequential episodes of dengue - Puerto Rico, 2005-2010
Sharp TM , Hunsperger E , Munoz-Jordan JL , Margolis HS , Tomashek KM . Am J Trop Med Hyg 2014 91 (2) 235-239 Of 53,633 suspected dengue cases reported to a passive dengue surveillance system in Puerto Rico during 2005-2010, 949 individuals were reported on more than one occasion and 21 had laboratory-confirmed dengue on two separate occasions. Median time between episodes was 2.9 years (range: 62 days-5.3 years). Seventeen (81%) individuals with sequential episodes of dengue were male, and seven (33%) were adults. All 21 individuals had one episode and seven (33%) individuals had both episodes during an epidemic that occurred in 2010. These observations show that heterotypic dengue virus immunity that protects against illness may have considerable variability but typically does not last longer than approximately 3 years. |
Burden of dengue infection and disease in a pediatric cohort in urban Sri Lanka
Tissera H , Amarasinghe A , De Silva AD , Kariyawasam P , Corbett KS , Katzelnick L , Tam C , Letson GW , Margolis HS , de Silva AM . Am J Trop Med Hyg 2014 91 (1) 132-7 Dengue is the most significant arthropod-borne viral infection of humans. Persons infected with dengue viruses (DENV) have subclinical or clinically apparent infections ranging from undifferentiated fever to dengue hemorrhagic fever/shock syndrome. Although recent studies estimated that the Indian subcontinent has the greatest burden of DENV infection and disease worldwide, we do not have reliable, population-based estimates of the incidence of infection and disease in this region. The goal of this study was to follow-up a cohort of 800 children living in a heavily urbanized area of Colombo, Sri Lanka to obtain accurate estimates of the incidence of DENV infection and disease. Annual blood samples were obtained from all children to estimate dengue seroprevalence at enrollment and to identify children exposed to new DENV infections during the study year. Blood was also obtained from any child in whom fever developed over the course of the study year to identify clinically apparent DENV infections. At enrollment, dengue seroprevalence was 53.07%, which indicated high transmission in this population. Over the study year, the incidence of DENV infection and disease were 8.39 (95% confidence interval = 6.56-10.53) and 3.38 (95% confidence interval = 2.24-4.88), respectively, per 100 children per year. The ratio of clinically inapparent to apparent infections was 1.48. These results will be useful for obtaining more accurate estimates of the burden of dengue in the region and for making decisions about testing and introduction of vaccines. |
Virus-specific differences in rates of disease during the 2010 dengue epidemic in Puerto Rico
Sharp TM , Hunsperger E , Santiago GA , Munoz-Jordan JL , Santiago LM , Rivera A , Rodriguez-Acosta RL , Gonzalez Feliciano L , Margolis HS , Tomashek KM . PLoS Negl Trop Dis 2013 7 (4) e2159 BACKGROUND: Dengue is a potentially fatal acute febrile illness (AFI) caused by four mosquito-transmitted dengue viruses (DENV-1-4) that are endemic in Puerto Rico. In January 2010, the number of suspected dengue cases reported to the passive dengue surveillance system exceeded the epidemic threshold and an epidemic was declared soon after. METHODOLOGY/PRINCIPAL FINDINGS: To characterize the epidemic, surveillance and laboratory diagnostic data were compiled. A suspected case was a dengue-like AFI in a person reported by a health care provider with or without a specimen submitted for diagnostic testing. Laboratory-positive cases had: (i) DENV nucleic acid detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in an acute serum specimen; (ii) anti-DENV IgM antibody detected by ELISA in any serum specimen; or (iii) DENV antigen or nucleic acid detected in an autopsy-tissue specimen. In 2010, a total of 26,766 suspected dengue cases (7.2 per 1,000 residents) were identified, of which 46.6% were laboratory-positive. Of 7,426 RT-PCR-positive specimens, DENV-1 (69.0%) and DENV-4 (23.6%) were detected more frequently than DENV-2 (7.3%) and DENV-3 (<0.1%). Nearly half (47.1%) of all laboratory-positive cases were adults, 49.7% had dengue with warning signs, 11.1% had severe dengue, and 40 died. Approximately 21% of cases were primary DENV infections, and 1-4 year olds were the only age group for which primary infection was more common than secondary. Individuals infected with DENV-1 were 4.2 (95% confidence interval [CI]: 1.7-9.8) and 4.0 (95% CI: 2.4-6.5) times more likely to have primary infection than those infected with DENV-2 or -4, respectively. CONCLUSIONS/SIGNIFICANCE: This epidemic was long in duration and yielded the highest incidence of reported dengue cases and deaths since surveillance began in Puerto Rico in the late 1960's. This epidemic re-emphasizes the need for more effective primary prevention interventions to reduce the morbidity and mortality of dengue. |
Dengue infection in children in Ratchaburi, Thailand: a cohort study. I. Epidemiology of symptomatic acute dengue infection in children, 2006-2009
Sabchareon A , Sirivichayakul C , Limkittikul K , Chanthavanich P , Suvannadabba S , Jiwariyavej V , Dulyachai W , Pengsaa K , Margolis HS , Letson GW . PLoS Negl Trop Dis 2012 6 (7) e1732 BACKGROUND: There is an urgent need to field test dengue vaccines to determine their role in the control of the disease. Our aims were to study dengue epidemiology and prepare the site for a dengue vaccine efficacy trial. METHODS AND FINDINGS: We performed a prospective cohort study of children in primary schools in central Thailand from 2006 through 2009. We assessed the epidemiology of dengue by active fever surveillance for acute febrile illness as detected by school absenteeism and telephone contact of parents, and dengue diagnostic testing. Dengue accounted for 394 (6.74%) of the 5,842 febrile cases identified in 2882, 3104, 2717 and 2312 student person-years over the four years, respectively. Dengue incidence was 1.77% in 2006, 3.58% in 2007, 5.74% in 2008 and 3.29% in 2009. Mean dengue incidence over the 4 years was 3.6%. Dengue virus (DENV) types were determined in 333 (84.5%) of positive specimens; DENV serotype 1 (DENV-1) was the most common (43%), followed by DENV-2 (29%), DENV-3 (20%) and DENV-4 (8%). Disease severity ranged from dengue hemorrhagic fever (DHF) in 42 (10.5%) cases, dengue fever (DF) in 142 (35.5%) cases and undifferentiated fever (UF) in 210 (52.5%) cases. All four DENV serotypes were involved in all disease severity. A majority of cases had secondary DENV infection, 95% in DHF, 88.7% in DF and 81.9% in UF. Two DHF (0.5%) cases had primary DENV-3 infection. CONCLUSION: The results illustrate the high incidence of dengue with all four DENV serotypes in primary school children, with approximately 50% of disease manifesting as mild clinical symptoms of UF, not meeting the 1997 WHO criteria for dengue. Severe disease (DHF) occurred in one tenth of cases. Data of this type are required for clinical trials to evaluate the efficacy of dengue vaccines in large scale clinical trials. |
Dengue: a potential transfusion-transmitted disease
Tomashek KM , Margolis HS . Transfusion 2011 51 (8) 1654-60 Dengue is caused by four related RNA viruses of the genus Flavivirus, dengue virus (DENV)−1, −2, −3, and −4. Infection with DENV is usually asymptomatic but each DENV is capable of causing the full spectrum of clinical disease from mild, undifferentiated acute febrile illness, to classic dengue fever and more severe disease including dengue hemorrhagic fever and dengue shock syndrome. Severe disease manifestations including hypovolemic shock and clinically significant hemorrhage are more commonly observed among patients during their second or subsequent episodes of DENV infection.1 Infection with one DENV produces lifelong immunity against that DENV type and short-term (≤2 months) cross-protection against infection with the other three DENVs. Therefore, an individual has a lifetime risk of up to four DENV infections. | DENVs are transmitted from person to person through the bite of an infected Aedes aegypti mosquito (less commonly Aedes albopictus or Aedes polynesiensis).2 Unlike other related flaviviruses such as West Nile virus, humans are the main amplifying host for DENV. While there is a sylvatic nonhuman primate cycle of DENV transmission, it rarely crosses to humans, and antibodies to the sylvatic virus appear to protect against human DENV. The transmission cycle begins when a mosquito ingests DENV in a blood meal from an infected person (Fig. 1). DENV replicates and disseminates within the mosquito and reaches the salivary glands after 8 to 12 days (extrinsic incubation period). Higher ambient temperatures may reduce the extrinsic incubation period and increase the chance they will infect a human before dying.3 The mosquito remains infectious for life (typically less than 1 month) and can transmit infection with 102 viral particles.4 DENV replicates in humans for an intrinsic incubation period of 3 to 14 days before symptom onset. Infected persons can transmit DENV to mosquitoes as early as 1 to 2 days before symptoms develop5 and throughout the approximately 7-day viremic period. Infected persons, even those who remain asymptomatic, have concentrations as high as 107 viral RNA copies per milliliter of blood.6,7 |
Dengue virus infection in Africa
Amarasinghe A , Kuritsk JN , Letson GW , Margolis HS . Emerg Infect Dis 2011 17 (8) 1349-54 Reported incidence of dengue has increased worldwide in recent decades, but little is known about its incidence in Africa. During 1960-2010, a total of 22 countries in Africa reported sporadic cases or outbreaks of dengue; 12 other countries in Africa reported dengue only in travelers. The presence of disease and high prevalence of antibody to dengue virus in limited serologic surveys suggest endemic dengue virus infection in all or many parts of Africa. Dengue is likely underrecognized and underreported in Africa because of low awareness by health care providers, other prevalent febrile illnesses, and lack of diagnostic testing and systematic surveillance. Other hypotheses to explain low reported numbers of cases include cross-protection from other endemic flavivirus infections, genetic host factors protecting against infection or disease, and low vector competence and transmission efficiency. Population-based studies of febrile illness are needed to determine the epidemiology and true incidence of dengue in Africa. |
Health economics of dengue: a systematic literature review and expert panel's assessment
Beatty ME , Beutels P , Meltzer MI , Shepard DS , Hombach J , Hutubessy R , Dessis D , Coudeville L , Dervaux B , Wichmann O , Margolis HS , Kuritsky JN . Am J Trop Med Hyg 2011 84 (3) 473-488 Dengue vaccines are currently in development and policymakers need appropriate economic studies to determine their potential financial and public health impact. We searched five databases (PubMed, EMBASE, LILAC, EconLit, and WHOLIS) to identify health economics studies of dengue. Forty-three manuscripts were identified that provided primary data: 32 report economic burden of dengue and nine are comparative economic analyses assessing various interventions. The remaining two were a willingness-to-pay study and a policymaker survey. An expert panel reviewed the existing dengue economic literature and recommended future research to fill information gaps. Although dengue is an important vector-borne disease, the economic literature is relatively sparse and results have often been conflicting because of use of inconsistent assumptions. Health economic research specific to dengue is urgently needed to ensure informed decision making on the various options for controlling and preventing this disease. |
Evaluation of diagnostic tests: dengue
Peeling RW , Artsob H , Pelegrino JL , Buchy P , Cardoso MJ , Devi S , Enria DA , Jeremy F , Gubler DJ , Guzman MC , Halstead SB , Hunsperger E , Kliks S , Margolis HS , Nathanson CM , Vinh CN , Rizzo N , Vazquez S , Yoksan S . Nat Rev Microbiol 2010 8 S30-8 Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. | Dengue virus infections can result in a range of clinical manifestations from asymptomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/DSS, which differentiates it from DF. DHF/DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Jun 24, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure