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1.
  • Ades, A. E., et al. (author)
  • Zika virus infection in pregnancy : a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia
  • 2020
  • In: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 10:12
  • Journal article (peer-reviewed)abstract
    • Introduction: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean.Methods and analysis: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach.Ethics and dissemination: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.
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2.
  • Amaku, M, et al. (author)
  • Magnitude and frequency variations of vector-borne infection outbreaks using the Ross-Macdonald model : explaining and predicting outbreaks of dengue fever
  • 2016
  • In: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 144:16, s. 3435-3450
  • Journal article (peer-reviewed)abstract
    • The classical Ross-Macdonald model is often utilized to model vector-borne infections; however, this model fails on several fronts. First, using measured (or estimated) parameters, which values are accepted from the literature, the model predicts a much greater number of cases than what is usually observed. Second, the model predicts a single large outbreak that is followed by decades of much smaller outbreaks, which is not consistent with what is observed. Usually towns or cities report a number of recurrences for many years, even when environmental changes cannot explain the disappearance of the infection between the peaks. In this paper, we continue to examine the pitfalls in modelling this class of infections, and explain that, if properly used, the Ross-Macdonald model works and can be used to understand the patterns of epidemics and even, to some extent, be used to make predictions. We model several outbreaks of dengue fever and show that the variable pattern of yearly recurrence (or its absence) can be understood and explained by a simple Ross-Macdonald model modified to take into account human movement across a range of neighbourhoods within a city. In addition, we analyse the effect of seasonal variations in the parameters that determine the number, longevity and biting behaviour of mosquitoes. Based on the size of the first outbreak, we show that it is possible to estimate the proportion of the remaining susceptible individuals and to predict the likelihood and magnitude of the eventual subsequent outbreaks. This approach is described based on actual dengue outbreaks with different recurrence patterns from some Brazilian regions.
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3.
  • Amaku, Marcos, et al. (author)
  • Modelling the test, trace and quarantine strategy to control the COVID-19 epidemic in the state of Sao Paulo, Brazil
  • 2021
  • In: Infectious Disease Modelling. - : KeAi Communications. - 2468-0427. ; 6, s. 46-55
  • Journal article (peer-reviewed)abstract
    • Testing for detecting the infection by SARS-CoV-2 is the bridge between the lockdown and the opening of society. In this paper we modelled and simulated a test-trace-and-quarantine strategy to control the COVID-19 outbreak in the State of Sao Paulo, Brasil. The State of Sao Paulo failed to adopt an effective social distancing strategy, reaching at most 59% in late March and started to relax the measures in late June, dropping to 41% in 08 August. Therefore, Sao Paulo relies heavily on a massive testing strategy in the attempt to control the epidemic.Two alternative strategies combined with economic evaluations were simulated. One strategy included indiscriminately testing the entire population of the State, reaching more than 40 million people at a maximum cost of 2.25 billion USD, that would reduce the total number of cases by the end of 2020 by 90%. The second strategy investigated testing only symptomatic cases and their immediate contacts - this strategy reached a maximum cost of 150 million USD but also reduced the number of cases by 90%. The conclusion is that if the State of Sao Paulo had decided to adopt the simulated strategy on April the 1st, it would have been possible to reduce the total number of cases by 90% at a cost of 2.25 billion US dollars for the indiscriminate strategy but at a much smaller cost of 125 million US dollars for the selective testing of symptomatic cases and their contacts. 
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4.
  • Angelo, Kristina M., et al. (author)
  • Zika among international travellers presenting to GeoSentinel sites, 2012-2019 : implications for clinical practice
  • 2020
  • In: Journal of Travel Medicine. - : Oxford University Press. - 1195-1982 .- 1708-8305. ; 27:4
  • Journal article (peer-reviewed)abstract
    • Introduction: International travellers contribute to the rapid spread of Zika virus (ZIKV) and its sentinel identification globally. We describe ZIKV infections among international travellers seen at GeoSentinel sites with a focus on ZIKV acquired in the Americas and the Caribbean, describe countries of exposure and traveller characteristics, and assess ZIKV diagnostic testing by site. Methods: Records with an international travel-related diagnosis of confirmed or probable ZIKV from January 2012 through December 2019 reported to GeoSentinel with a recorded illness onset date were included to show reported cases over time. Records from March 2016 through December 2019 with an exposure region of the Americas or the Caribbean were included in the descriptive analysis. A survey was conducted to assess the availability, accessibility and utilization of ZIKV diagnostic tests at GeoSentinel sites. Results: GeoSentinel sites reported 525 ZIKV cases from 2012 through 2019. Between 2012 and 2014, eight cases were reported, and all were acquired in Asia or Oceania. After 2014, most cases were acquired in the Americas or the Caribbean, a large decline in ZIKV cases occurred in 2018-19. Between March 2016 and December 2019, 423 patients acquired ZIKV in the Americas or the Caribbean, peak reporting to these regions occurred in 2016 [330 cases (78%)]. The median age was 36 years (range: 3-92); 63% were female. The most frequent region of exposure was the Caribbean (60%). Thirteen travellers were pregnant during or after travel; one had a sexually acquired ZIKV infection. There was one case of fetal anomaly and two travellers with Guillain-Barre syndrome. GeoSentinel sites reported various challenges to diagnose ZIKV effectively. Conclusion: ZIKV should remain a consideration for travellers returning from areas with risk of ZIKV transmission. Travellers should discuss their travel plans with their healthcare providers to ensure ZIKV prevention measures are taken.
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5.
  • Balasingam, Shobana, et al. (author)
  • Randomized controlled trials for influenza drugs and vaccines : a review of controlled human infection studies
  • 2016
  • In: International Journal of Infectious Diseases. - : Elsevier. - 1201-9712 .- 1878-3511. ; 49, s. 18-29
  • Research review (peer-reviewed)abstract
    • OBJECTIVES: Controlled human infection, the intentional infection of healthy volunteers, allows disease pathogenesis to be studied and vaccines and therapeutic interventions to be evaluated in a controlled setting. A systematic review of randomized controlled trials of countermeasures for influenza that used the experimental human infection platform was performed. The primary objective was to document the scope of trials performed to date and the main efficacy outcome in the trials. The secondary objective was to assess safety and identify serious adverse events.METHODS: The PubMed database was searched for randomized controlled influenza human challenge studies with predetermined search terms. Review papers, papers without outcomes, community-acquired infections, duplicated data, pathogenesis studies, and observational studies were excluded.RESULTS: Twenty-six randomized controlled trials published between 1947 and 2014 fit the study inclusion criteria. Two-thirds of these trials investigated antivirals and one-third investigated influenza vaccines. Among 2462 subjects inoculated with influenza virus, the incidence of serious adverse events was low (0.04%). These challenge studies helped to down-select three antivirals and one vaccine that were subsequently approved by the US Food and Drug Administration (FDA).CONCLUSIONS: Controlled human infection studies are an important research tool in assessing promising influenza vaccines and antivirals. These studies are performed quickly and are cost-effective and safe, with a low incidence of serious adverse events.
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6.
  • Banks, S. D., et al. (author)
  • Insecticide-treated clothes for the control of vector-borne diseases : a review on effectiveness and safety
  • 2014
  • In: Medical and Veterinary Entomology. - : Wiley. - 0269-283X .- 1365-2915. ; 28:S1, s. 14-25
  • Research review (peer-reviewed)abstract
    • Insecticide-treated clothing has been used for many years by the military and in recreational activities as personal protection against bites from a variety of arthropods including ticks, chigger mites, sandflies and mosquitoes. Permethrin is the most commonly used active ingredient, but others, including bifenthrin, deltamethrin, cyfluthrin, DEET (N,N-diethyl-3-methylbenz-amide) and KBR3023, have also been trialled. Treatment is usually carried out by home or factory dipping. However, new microencapsulation technologies which may prolong the activity of insecticides on clothing are now available and may help to overcome the inevitable reduction in efficacy over time that occurs as a result of washing, ultraviolet light exposure, and the normal wear and tear of the fabric. The aim of this article is to review the evidence base for the use of insecticide-treated clothing for protection against bites from arthropods and its effect on arthropod-borne pathogen transmission. Although some studies do demonstrate protection against pathogen transmission, there are surprisingly few, and the level of protection provided varies according to the disease and the type of study conducted. For example, insecticide-treated clothing has been reported to give between 0% and 75% protection against malaria and between 0% and 79% protection against leishmaniasis. Studies vary in the type of treatment used, the age group of participants, the geographical location of the study, and the pathogen transmission potential. This makes it difficult to compare and assess intervention trials. Overall, there is substantial evidence that insecticide-treated clothing can provide protection against arthropod bites. Bite protection evidence suggests that insecticide-treated clothing may be useful in the prevention of pathogen transmission, but further investigations are required to accurately demonstrate transmission reduction.
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7.
  • Banks, S De Raedt, et al. (author)
  • Permethrin-treated clothing as protection against the dengue vector, Aedes aegypti : extent and duration of protection
  • 2015
  • In: Tropical medicine & international health. - : Wiley-Blackwell. - 1360-2276 .- 1365-3156. ; 20:Suppl. 1, s. 399-400
  • Journal article (other academic/artistic)abstract
    • Background: 3900 million people globally are at risk of dengue fever infection, with its distribution increasing rapidly over the past 50 years. Since the primary vector, Aedes aegypti, is exophilic and most active during the day, personal protection technologies, such as insecticide treated clothing, could provide significant protection from mosquito bites.Methods: World Health Organisation Pesticide Evaluation Scheme (WHOPES) cone and arm-in-cage assays were used to assess protection, knockdown and mortality against factory, home-dipped and microencapsulated permethrin-treated fabrics using Ae. aegypti mosquitoes. Factory-treated clothing was then analysed further to investigate the effects of insecticide resistance, clothing coverage, washing, Ultra-violet light and ironing.Results: Factory-treated clothing showed the greatest protective effect (1 h KD 96.5% and 24 h mortality 97.1%), landing protection (59% (95% CI = 49.2–66.9) and bite protection (100%). Landing and biting protection reduced significantly from 58.9% to 18.5% and 28.6% to 11.1% after 10 washes for simulated hand washing. Resistance to permethrin had no effect on the efficacy of the clothing, with coverage playing an important role. Full coverage provided the highest protection (79.4% landing protection, 100% biting protection). Free flight room assays showed no difference in landing protection between the two coverage types but bite protection was significantly greater (>90%) with full coverage. HPLC confirmed ironing reduced permethrin content after 1 week simulated use, with a 96.7% decrease after 3 months. UV exposure was shown to have no effect.Conclusion: Insecticide treated clothing can provide significant biting and landing protection, even in a resistant strain. However, our findings also suggest that clothing may provide only short-term protection due to the effect of washing and ironing, highlighting the need for improved clothing treatment techniques.Disclosure: Nothing to disclose.
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8.
  • Boeras, Debi, et al. (author)
  • Evaluation of Zika rapid tests as aids for clinical diagnosis and epidemic preparedness
  • 2022
  • In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 49
  • Journal article (peer-reviewed)abstract
    • Background: Development and evaluation of diagnostics for diseases of epidemic potential are often funded during epidemics, but not afterwards, leaving countries unprepared for the next epidemic. United Nations Children's Emergency Fund (UNICEF) partnered with the United States Agency for International Development (USAID) to address this important gap by investing in an advance purchase commitment (APC) mechanism to accelerate the development and evaluation of Zika rapid diagnostic tests (RDTs) for case detection and surveillance. This paper describes the performance evaluation of five Zika RDTs eligible for procurement.Methods: A network of European Union-funded ZikaPLAN sites in Africa, Asia, Latin America with access to relevant serum specimens were selected to evaluate RDTs developed for the UNICEF APC mechanism. A standardised protocol and evaluation panels were developed and a call for specimens for the evaluation panels issued to different sites. Each site contributed specimens to the evaluation from their biobank. Data were collated, analysed and presented to the UNICEF Procurement Review Group for review.Findings: Three RDTs met the criteria for UNICEF procurement of sensitivity and specificity of 85% against a refence standard. The sensitivity/specificity of the ChemBio anti-Zika Virus (ZIKV) immunoglobulin M (IgM) test was 86.4 %/86.7% and the ChemBio ZCD system for anti-ZIKV IgM was 79.0%/97.1%, anti-dengue virus (DENV) IgM 90.0%/89.2%, anti-Chikungunya virus (CHIKV) IgM 90.6%/97.2%. The sensitivity/specificity of the SD Biosensor anti-ZIKV IgM was 96.8 %/90.8%, anti-DENV IgM 71.8%/83.5%, the DENV nonstructural protein 1 (NS1) glycoprotein 90.0%/90.2%, anti- yellow fever virus (YFV) IgM 84.6%/92.4%, anti-CHIKV IgM 86.3%/97.5%.Interpretation: Three RDTs fulfilled the performance thresholds set by WHO and were eligible for UNICEF procurement. These tests will improve the diagnosis of ZIKV and other arboviral infections as well as providing countries with better tools for surveillance and response to future epidemics.
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9.
  • Boggild, Andrea K, et al. (author)
  • Latitudinal patterns of travel among returned travelers with influenza : results from the GeoSentinel Surveillance Network, 1997-2007.
  • 2012
  • In: Journal of Travel Medicine. - : John Wiley & Sons. - 1195-1982 .- 1708-8305. ; 19:1, s. 4-8
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Influenza is a common vaccine-preventable disease among international travelers, but few data exist to guide use of reciprocal hemisphere or out-of-season vaccines. METHODS: We analyzed records of ill-returned travelers in the GeoSentinel Surveillance Network to determine latitudinal travel patterns in those who acquired influenza abroad. RESULTS: Among 37,542 ill-returned travelers analyzed, 59 were diagnosed with influenza A and 11 with influenza B. Half of travelers from temperate regions to the tropics departed outside influenza season. Twelve travelers crossed hemispheres from one temperate region to another, five during influenza season. Ten of 12 travelers (83%) with influenza who crossed hemispheres were managed as inpatients. Proportionate morbidity estimates for influenza A acquisition were highest for travel to the East-Southeast Asian influenza circulation network with 6.13 (95% CI 4.5-8.2) cases per 1000 ill-returned travelers, a sevenfold increased proportionate morbidity compared to travel outside the network. CONCLUSIONS: Alternate hemisphere and out-of-season influenza vaccine availability may benefit a small proportion of travelers. Proportionate morbidity estimates by region of travel can inform pre-travel consultation and emphasize the ease of acquisition of infections such as influenza during travel.
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12.
  • Capasso, Ariadna, et al. (author)
  • Incidence of Guillain-Barre Syndrome (GBS) in Latin America and the Caribbean before and during the 2015-2016 Zika virus epidemic : A systematic review and meta-analysis
  • 2019
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:8
  • Research review (peer-reviewed)abstract
    • Background: A severe neurological disorder, Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. Enhanced surveillance of GBS in Latin America and the Caribbean (LAC) following the 2015–2016 Zika virus (ZIKV) epidemic presents an opportunity to estimate, for the first time, the regional incidence of GBS.Methods and findings: For this systematic review and meta-analysis, we searched nine scientific databases and grey literature from January 1, 1980 to October 1, 2018. Sources with primary data on incident GBS cases in LAC within a well-defined population and timeframe, published in English, Spanish, Portuguese, or French, were included. We calculated the annual GBS incidence rates (IRs) and 95% confidence intervals (CIs) for each source based on published data. Following an assessment of heterogeneity, we used random-effects meta-analysis to calculate the pooled annual IR of GBS. The study is registered with PROSPERO, number CRD42018086659. Of the 6568 initial citation hits, 31 were eligible for inclusion. Background annual GBS IRs in Latin America ranged from 0.40 in Brazil to 2.12/100,000 in Chile. The pooled annual IR in the Caribbean was 1.64 (95% CI 1.29–2.12, I2<0.01, p = 0.44). During the ZIKV epidemic, GBS IRs ranged from 0.62 in Mexico to 9.35/100,000 in Martinique. GBS increased 2.6 (95% CI 2.3–2.9) times during ZIKV and 1.9 (95% CI 1.1–3.4) times during chikungunya outbreaks over background rates. A limitation of this review is that the studies included employed different methodologies to find and ascertain cases of GBS, which could contribute to IR heterogeneity. In addition, it is important to consider that data on GBS are lacking for many countries in the region.Conclusions: Background IRs of GBS appear to peak during arboviral disease outbreaks. The current review contributes to an understanding of the epidemiology of GBS in the LAC region, which can inform healthcare system planning and preparedness, particularly during arboviral epidemics.
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13.
  • Chen, Lin H, et al. (author)
  • Vaccination of travelers : how far have we come and where are we going?
  • 2011
  • In: Expert review of vaccines. - : Informa UK Limited. - 1744-8395 .- 1476-0584. ; 10:11, s. 1609-20
  • Journal article (peer-reviewed)abstract
    • Vaccine recommendations are a prominent part of health preparations before international travel. We review progress made in the past decade regarding vaccines used primarily by persons traveling from high-income countries to low- and middle-income countries. The combined hepatitis A-B vaccine, the recently licensed Vero cell-derived Japanese encephalitis vaccine and conjugated quadrivalent meningococcal vaccines are discussed. This article provides updates on yellow fever vaccine-associated visceral and neurologic adverse events, indications for influenza vaccine in travelers, the rapid immunization schedule for tick-borne encephalitis vaccine, schedules for postexposure rabies prophylaxis, and new insights about oral cholera vaccines following the outbreak in Haiti. The future should bring vaccines for serogroup B Neiserria meningitidis, dengue and malaria, as well as an inactivated yellow fever vaccine.
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14.
  • Depoux, Anneliese, et al. (author)
  • The pandemic of social media panic travels faster than the COVID-19 outbreak
  • 2020
  • In: Journal of Travel Medicine. - : Oxford University Press. - 1195-1982 .- 1708-8305. ; 27:3
  • Journal article (peer-reviewed)abstract
    • We need to rapidly detect and respond to public rumours, perceptions, attitudes and behaviours around COVID-19 and control measures. The creation of an interactive platform and dashboard to provide real-time alerts of rumours and concerns about coronavirus spreading globally would enable public health officials and relevant stakeholders to respond rapidly with a proactive and engaging narrative that can mitigate misinformation.
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15.
  • DeRaedt Banks, Sarah, et al. (author)
  • Permethrin-Treated Clothing as Protection against the Dengue Vector, Aedes aegypti : Extent and Duration of Protection
  • 2015
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 9:10
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Dengue transmission by the mosquito vector, Aedes aegypti, occurs indoors and outdoors during the day. Personal protection of individuals, particularly when outside, is challenging. Here we assess the efficacy and durability of different types of insecticide-treated clothing on laboratory-reared Ae. aegypti.METHODS: Standardised World Health Organisation Pesticide Evaluation Scheme (WHOPES) cone tests and arm-in-cage assays were used to assess knockdown (KD) and mortality of Ae. aegypti tested against factory-treated fabric, home-dipped fabric and microencapsulated fabric. Based on the testing of these three different treatment types, the most protective was selected for further analysis using arm-in cage assays with the effect of washing, ultra-violet light, and ironing investigated using high pressure liquid chromatography.RESULTS: Efficacy varied between the microencapsulated and factory dipped fabrics in cone testing. Factory-dipped clothing showed the greatest effect on KD (3 min 38.1%; 1 hour 96.5%) and mortality (97.1%) with no significant difference between this and the factory dipped school uniforms. Factory-dipped clothing was therefore selected for further testing. Factory dipped clothing provided 59% (95% CI = 49.2%- 66.9%) reduction in landing and a 100% reduction in biting in arm-in-cage tests. Washing duration and technique had a significant effect, with insecticidal longevity shown to be greater with machine washing (LW50 = 33.4) compared to simulated hand washing (LW50 = 17.6). Ironing significantly reduced permethrin content after 1 week of simulated use, with a 96.7% decrease after 3 months although UV exposure did not reduce permethrin content within clothing significantly after 3 months simulated use.CONCLUSION: Permethrin-treated clothing may be a promising intervention in reducing dengue transmission. However, our findings also suggest that clothing may provide only short-term protection due to the effect of washing and ironing, highlighting the need for improved fabric treatment techniques.
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16.
  • Durbin, Anna, et al. (author)
  • An update on Zika vaccine developments
  • 2017
  • In: Expert Review of Vaccines. - : TAYLOR & FRANCIS LTD. - 1476-0584 .- 1744-8395. ; 16:8, s. 781-787
  • Journal article (peer-reviewed)abstract
    • Introduction: The devastating consequences of congenital Zika virus (ZIKV) infection led to a global response directed toward a better understanding of the epidemiology and pathogenesis of ZIKV and to efforts at vaccine development. As a result, there are currently 45 ZIKV vaccine candidates in development. Areas covered: Both traditional (purified inactivated, live attenuated, viral-vectored, recombinant sub-unit) and novel (DNA, self-replicating RNA, mRNA) vaccine platforms are being utilized. For emergency use, vaccines that are appropriate for women of child-bearing age (including pregnant women) are being developed. Live vaccines that may be contraindicated in pregnancy are also in development for potential inclusion in national immunization programmes in childhood or pre-teenage age groups. WHO developed a target product profile for Zika vaccines for use in an emergency. Expert commentary: Although ZIKV vaccine development had a quick head start, further development may be hampered because of the inability to conduct large efficacy trials with the decline in cases globally and unpredictability of new outbreaks. Furthermore, there are complex ethical issues involved in conducting efficacy trials in pregnant women.
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17.
  • Earnest, A, et al. (author)
  • Meteorological factors and El Niño Southern Oscillation are independently associated with dengue infections
  • 2012
  • In: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 140:07, s. 1244-1251
  • Journal article (peer-reviewed)abstract
    • Our objective was to determine the association between temperature, humidity, rainfall and dengue activity in Singapore, after taking into account lag periods as well as long-term climate variability such as the El Niño Southern Oscillation Index (SOI). We used a Poisson model which allowed for autocorrelation and overdispersion in the data. We found weekly mean temperature and mean relative humidity as well as SOI to be significantly and independently associated with dengue notifications. There was an interaction effect by periods of dengue outbreaks, but periods where El Niño was present did not moderate the relationship between humidity and temperature with dengue notifications. Our results help to understand the temporal trends of dengue in Singapore, and further reinforce the findings that meteorological factors are important in the epidemiology of dengue.
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18.
  • Fernando, Enoka Sonali, et al. (author)
  • Household and Hospitalization Costs of Pediatric Dengue Illness in Colombo, Sri Lanka
  • 2021
  • In: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 105:1, s. 110-116
  • Journal article (peer-reviewed)abstract
    • Dengue, a mosquito-borne viral infection that affects millions around the world, poses a substantial economic burden in endemic countries. We conducted a prospective costing study in hospitalized pediatric dengue patients at the Lady Ridgeway Hospital for Children (LRHC), a public pediatric hospital in Colombo district, Sri Lanka, to assess household out-of-pocket and hospitalization costs of dengue in pediatric patients during peak dengue transmission season. Between August and October 2013, we recruited 216 hospitalized patients (aged 0-3 years, 27%; 4-7 years, 29%; 8-12 years, 42%) who were clinically or laboratory diagnosed with dengue. Using 2013 US dollars, household outof-pocket spending, on average, was US$59 (SD 49) per episode and increased with disease severity (DF, US$52; DHF/ DSS, US$78). Pediatric dengue patients received free-of-charge medical care during hospitalization at LRHC, and this places a high financial burden on hospitals. The direct medical cost of hospitalization was US$68 (SD 31.4) for DF episode, and US$122.7 (SD 65.2) for DHF/DSS episode. Yet a hospitalized dengue illness episode still accounted for 20% to 35% of household monthly income due to direct and indirect costs. Additionally, a majority of caregivers (70%) sought outpatient care before hospitalization, most of whom (81%) visited private health facilities. Our findings indicate that hospitalized pediatric dengue illness poses a nontrivial cost burden to households and healthcare systems, emphasizing the importance of preventing and controlling the transmission of dengue in endemic countries.
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19.
  • Flores-Figueroa, Jose, et al. (author)
  • Patterns of illness in travelers visiting Mexico and Central America : the GeoSentinel experience.
  • 2011
  • In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press. - 1537-6591. ; 53:6, s. 523-531
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Mexico and Central America are important travel destinations for North American and European travelers. There is limited information on regional differences in travel related morbidity. METHODS: We describe the morbidity among 4779 ill travelers returned from Mexico and Central America who were evaluated at GeoSentinel network clinics during December 1996 to February 2010. RESULTS: The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. A higher proportion of ill travelers from the United States had acute diarrhea, compared with their Canadian and European counterparts (odds ratio, 1.9; P < .0001). During the 2009 H1N1 influenza outbreak from March 2009 through February 2010, the proportionate morbidity (PM) associated with respiratory illnesses in ill travelers increased among those returned from Mexico, compared with prior years (196.0 cases per 1000 ill returned travelers vs 53.7 cases per 1000 ill returned travelers; P < .0001); the PM remained constant in the rest of Central America (57.3 cases per 1000 ill returned travelers). We identified 50 travelers returned from Mexico and Central America who developed influenza, including infection due to 2009 H1N1 strains and influenza-like illness. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (PM, 2.2 cases per 1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis. CONCLUSIONS: Travel medicine practitioners advising and treating travelers visiting these regions should dedicate special attention to vaccine-preventable illnesses and should consider the uncommon occurrence of acute hepatitis A, leptospirosis, neurocysticercosis, acute Chagas disease, onchocerciasis, mucocutaneous leishmaniasis, neurocysticercosis, HIV, malaria, and brucellosis.
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21.
  • Franco, L, et al. (author)
  • Dengue in Africa : sustained and silent circulation of multiple serotypes and genotypes, detected in travelers from 2010 to 2014
  • 2015
  • In: Tropical medicine & international health. - : Wiley-Blackwell. - 1360-2276 .- 1365-3156. ; 20:Suppl. 1, s. 107-108
  • Journal article (other academic/artistic)abstract
    • Introduction: Dengue is caused by 4 different related viruses, DENV 1 to 4, transmitted to humans via Aedes mosquitoes. The disease is endemic in more than 100 countries. In Africa, the estimated dengue burden is 15 million of clinical cases and about 48 millions of inapparent infections. However, dengue remains largely unrecognized in Africa. Due to the lack of laboratory confirmation, a febrile syndrome is frequently misdiagnosed as malarial infection. The circulation of different dengue serotypes is also poorly documented. However, some information is provided by reports of dengue infections in travellers returning from Africa. In the present study we attempt the identification of dengue serotypes and genotypes circulating in Africa from 2010 to 2014 detected in travellers returning to Europe.Methods: We collected samples from viraemic travellers returning from Africa who attended TropNet clinics in Europé from 2010 to 2014. Sequences of the Envelope gene were used to identify the serotype and genotype.Results: During the study period we identified 3 DENV serotypes circulating in Africa. DENV 1 strains were detected in East Africa in 2010 (Eritrea) and in 2012 (Kenia), whereas in Central Africa in 2013(Angola and DRC). Strains from East Africa were grouped within Asian genotype, close to virus isolated in previous years in Djibouti and Kenia; we found American /African genotype in Central Africa. Both genotypes have circulated in West Africa for many years. DENV 2 strains were detected in West Africa (Senegal) and in East Africa (Tanzania) in 2014. Dengue 2 from Tanzania belongs to cosmopolitan genotype, but form a distinct clade different from the old African group. However, DENV 2 from Senegal surprisingly fell into genotype America /Asia. To our knowledge this is the first time identified in Africa. Finally, DENV 3 was detected in 2010 in Mali and Burkina Faso and again in Burkina Faso in 2013. All DENV 3 belong to genotype III and form a cluster with the African strains identified since 2008.Conclusion: DENV 1 of both genotypes was identified previously in Africa indicating endemic transmission as well as with DENV 3. Meanwhile, a new DENV 2 appeared in Tanzania, introduced from South East Asia, and in Senegal from the Americas. These results confirm silent and sustained circulation of dengue in Africa and show the usefulness of travelers for sentinel surveillance to unmask the dengue problem in Africa.Disclosure: Nothing to disclose.
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22.
  • Franco, L, et al. (author)
  • Dengue serotypes and genotypes circulating in recent years in the Caribbean and imported to Europe
  • 2015
  • In: Tropical medicine & international health. - : Wiley-Blackwell. - 1360-2276 .- 1365-3156. ; 20:Suppl. 1, s. 104-105
  • Journal article (other academic/artistic)abstract
    • Introduction: Dengue viruses (DENV) are the most widespread arthropod-borne viruses endemic in the tropics and transmitted to humans through the bites of Aedes mosquitoes. Travelers can act as vectors to introduce DENV to uninfected areas or regions. Travelers can also serve as sentinels for ongoing outbreaks and dominating serotypes and genotypes in the source countries. We set out to describe the importation of dengue virus from the Caribbean via travelers to Europe.Methods: From 2011 to 2014, we collected samples from viraemic travelers returning from the Caribbean with confirmed dengue to 11 TropNet clinics in Europe that are participating in the DengueTools project. Sequences of the Envelope gene were used to identify serotype and genotype.Results: The main countries of importation were Barbados, Cuba, Dominican Republic, Guadeloupe, Haiti, Martinique, Netherlands Antilles and Puerto Rico. All 4 DENV serotypes were identified. DENV 1 strains were grouped within genotype V creating a new clade. All DENV 2 sequences clustered within a clade in the American/Asian genotype which was recently also identified in other Caribbean and Brazilian strains. DENV 3 strains were grouped within genotype III. All DENV 4 strains were phylogenetically grouped within a modern Caribbean basin clade in genotype II.Conclusions: Travelers provides unique insights into the global picture of circulating DENV strains. This study from the Caribbean region led to the identification of novel clades. Moreover, we were be able to detect dengue strains circulating in Cuba from 2011 to 2013, although officially no dengue was reported during that time period. Travelers serve as sentinels to provide timely information about current distribution of dengue serotypes and genotypes associated or not with outbreaks and track the spread of DENV strains in areas with scarce epidemiological information.Disclosure: Nothing to disclose.
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23.
  • Franco, L., et al. (author)
  • Molecular epidemiology suggests Venezuela as the origin of the dengue outbreak in Madeira, Portugal in 2012-2013
  • 2015
  • In: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 21:7, s. 713.e5-713.e8
  • Journal article (peer-reviewed)abstract
    • An explosive epidemic occurred in Madeira Island (Portugal) from October 2012 to February 2013. Published data showed that dengue virus type 1 introduced from South America was the incriminated virus. We aim to determine the origin of the strain introduced to Madeira by travellers returning to Europe. Using phylogeographic analysis and complete envelope sequences we have demonstrated that the most probable origin of the strain is Venezuela.
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24.
  • Gaunt, Michael W., et al. (author)
  • Recombination of B- and T-cell epitope-rich loci from Aedes- and Culex-borne flaviviruses shapes Zika virus epidemiology
  • 2020
  • In: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 174
  • Journal article (peer-reviewed)abstract
    • Sporadic human Zika virus (ZIKV) infections have been recorded in Africa and Asia since the 1950s. Major epidemics occurred only after ZIKV emerged in the Pacific islands and spread to the Americas. Specific biological determinants of the explosive epidemic nature of ZIKV have not been identified. Phylogenetic studies revealed incongruence in ZIKV placement in relation to Aedes-borne dengue viruses (DENV) and Cu/ex-borne flaviviruses. We hypothesized that this incongruence reflects interspecies recombination resulting in ZIKV evasion of cross-protective T-cell immunity. We investigated ZIKV phylogenetic incongruence in relation to: DENV T-cell epitope maps experimentally identified ex vivo, published B-cell epitope loci, and CD8(+) T-cell epitopes predicted in silico for mosquito-borne flaviviruses. Our findings demonstrate that the ZIKV proteome is a hybrid of Aedes-borne DENV proteins interspersed amongst Cu/ex-borne flavivirus proteins derived through independent interspecies recombination events. These analyses infer that DENV-associated proteins in the ZIKV hybrid proteome generated immunodominant human B-cell responses, whereas ZIKV recombinant derived Cu/ex-borne flavivirus-associated proteins generated immunodominant CD8(+) and/or CD4(+) T-cell responses. In silico CD8(+) T-cell epitope ZIKV cross-reactive prediction analyses verified this observation. We propose that by acquiring cytotoxic T-cell epitope-rich regions from Cu/ex-borne flaviviruses, ZIKV evaded DENV-generated T-cell immune cross-protection. Thus, Cu/ex-borne flaviviruses, including West Nile virus and Japanese encephalitis virus, might induce cross-protective T-cell responses against ZIKV. This would explain why explosive ZIKV epidemics occurred in DENV-endemic regions of Micronesia, Polynesia and the Americas where Cu/ex-borne flavivirus outbreaks are infrequent and why ZIKV did not cause major epidemics in Asia where Culex-borne flaviviruses are widespread.
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25.
  • Gessner, Bradford D, et al. (author)
  • Estimating the public health importance of the CYD-tetravalent dengue vaccine : vaccine preventable disease incidence and numbers needed to vaccinate
  • 2016
  • In: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 34:20, s. 2397-2401
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: To evaluate the potential public health impact of the live attenuated tetravalent Sanofi Pasteur dengue vaccine (CYD-TDV) we analyzed data from the reported clinical trials to calculate vaccine preventable disease incidence (VPDI) and number needed to vaccinate (NNV) based on the licensure indication for persons age 9 years and above.METHODS: VPDI is defined as incidence in an unvaccinated population X vaccine efficacy (VE), and thus incorporates both VE and the underlying burden of disease. NNV was calculated as 100,000 divided by VPDI divided by 2-year length of study. We compared these values to data for three newer vaccines that are currently integrated into some national immunization programs in Asia and Latin America, namely pneumococcal conjugate, Haemophilus influenzae type b, and rotavirus vaccines.RESULTS: In the Asian-Pacific trial, in the first 25 months after the first dose of the dengue vaccine, CYD-TDV prevented annually 2639 cases of virologically confirmed dengue for every 100,000 persons vaccinated, for an NNV of 18. In the Latin American trial, given the overall lower annual dengue incidence compared to Asia, VPDI was 1707, and NNV 28. For the Asian-Pacific and Latin American studies, the VPDIs for hospitalized virologically confirmed disease at the trials' end were 638 and 239 per 100,000 population per year, respectively, with NNVs of 75 and 201. VPDI for confirmed dengue hospitalization was higher than that for Hib vaccine against Hib meningitis or all cause severe pneumonia while lower than that for rotavirus vaccine against severe rotavirus gastroenteritis.CONCLUSIONS: Our analysis found that the CYD-TDV dengue vaccine had favorable VPDI and NNV, also when compared to existing vaccines used in Latin America and Asia. VPDI and NNV varied by serotype distribution, extent of prior dengue exposure (baseline seroprevalence) and country. These findings will help policy-makers decide where and how to introduce this vaccine post-licensure.
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